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1.
Inj Epidemiol ; 11(1): 25, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872185

ABSTRACT

INTRODUCTION: Hand injuries constitute up to 30% of the total cases treated in emergency departments. Over time, demographic changes, especially an aging population, and shifts in workplace safety regulations and healthcare policies have significantly impacted the landscape of hand trauma. This study aims to identify and analyze these evolving trends over nearly two decades. METHODS: In this retrospective, cross-sectional study, we investigated patients who were admitted to the high-volume regional hand trauma center of a university hospital between January 2007 and December 2022. We analyzed trends in patients' demographics and annual alterations of injuries. For the comparative analysis, patients were divided into two groups based on the time of presentation: the early cohort (2007-2014) and the current cohort (2015-2022). RESULTS: A total of 14,414 patients were admitted to our emergency department within the study period. A significant annual increase in patient age was identified (R2 = 0.254, p = 0.047). The number of presentations increased annually by an average of 2% (p < 0.001). The incidence of the following hand injuries significantly increased: sprains/strains (+ 70.51%, p = 0.004), superficial lacerations (+ 53.99%, p < 0.001), joint dislocations (+ 51.28%, p < 0.001), fractures (carpal: + 49.25%, p = 0.003; noncarpal: + 39.18%, p < 0.001), deep lacerations (+ 37.16%, p < 0.001) and burns and corrosions (+ 29.45%, p < 0.001). However, rates of amputations decreased significantly (- 22.09%, p = 0.04). CONCLUSIONS: A consistent and significant annual increase in both the total number of injuries and the average age of patients was identified. An aging population may increase injury rates and comorbidities, stressing healthcare resources. Our study underscores the need to adapt healthcare structures and reimbursement policies, especially for outpatient hand injury care.

2.
Surg Innov ; : 15533506241262568, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38884216

ABSTRACT

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.

3.
Article in German | MEDLINE | ID: mdl-38748218

ABSTRACT

BACKGROUND: The occurrence of infections has always been feared in all surgical disciplines. Plastic reconstructive surgery faces the challenge of treating infection-related defects on a patient-specific basis, which requires a multidisciplinary treatment concept. Satisfactory treatment success can only be achieved through radical debridement for infection cleansing, optimization of the perfusion situation paired with targeted anti-infective treatment and, if necessary, with soft tissue reconstruction by plastic surgery. OBJECTIVE: This article presents the current possibilities of plastic and reconstructive surgery with respect to the reconstruction of infection-related defects. MATERIAL AND METHODS: Proven and reliable strategies are presented and supplemented by promising experimental approaches. RESULTS: Due to the often multilayered defect situation caused by infections, from the epidermis to cancellous bone, the entire armamentarium of plastic and reconstructive surgery is used for reconstruction. CONCLUSION: The early involvement of plastic surgery in the treatment of infections and the interdisciplinary and multimodal treatment approach have proven their worth in the treatment of complex infection situations.

4.
PLoS One ; 19(5): e0304215, 2024.
Article in English | MEDLINE | ID: mdl-38809926

ABSTRACT

The landscape mosaic model quantifies and maps the spatial juxtaposition of different land uses. It provides a landscape perspective of anthropic threats posed by agriculture and urban development, and the spatial-temporal shifting of the landscape mosaic indicates landscapes where anthropic intensity has changed. We use the U.S. Geological Survey provided National Land Cover Database (NLCD) for the years 2001 and 2021 to derive the landscape mosaic at five analysis scales. To improve earlier implementations of the model, we introduce the heatmap, a flexible scheme providing more thematic reporting opportunities and allowing for better quantitative summary reporting across analysis scales as well as for temporal trends. The results are exemplified at regional scale for the Atlanta metropolitan area. We use the improved model to investigate the land cover context over time and at different analysis scales and show how custom color tables detail different thematic features of the landscape mosaic, including the degree and change of anthropic intensity. We conclude with a discussion of potential applications in ecology, landscape planning, and restoration to illustrate the benefits of the revised landscape mosaic model. All assessment tools are now available in open-source software packages.


Subject(s)
Models, Theoretical , Conservation of Natural Resources/methods , Agriculture/methods , Humans , Ecosystem
5.
Ann Plast Surg ; 92(4): 469-473, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38470816

ABSTRACT

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.

6.
Handchir Mikrochir Plast Chir ; 56(2): 172-179, 2024 Apr.
Article in German | MEDLINE | ID: mdl-38437866

ABSTRACT

BACKGROUND: Patients affected by polyneuropathy often report pain, paraesthesia and numbness and are at risk of having an increased propensity to fall with the corresponding complications. In case of persistent symptoms after all conservative and medical treatment options have been exhausted, a nerve decompression in the lower leg as described by Dellon can lead to an improvement of the discomfort for many patients. This article presents our long-term results with Dellon's operation. METHODS: In this retrospective study, we included 33 patients with diabetic or idiopathic polyneuropathy in whom we performed Dellon's nerve decompression in the lower leg in the years 2011-2013. In 29 out of the 33 patients, we investigated the level of pain (according to the numeric rating scale NRS 0-10), paraesthesia, numbness, Hoffman-Tinel sign, and Semmes-Weinstein monofilaments three months postoperatively. 88 months postoperatively (range 78-111 months), we were able to contact 20 of the 33 patients with a questionnaire asking about their present pain level (NRS 0-10), satisfaction with the postoperative result (NRS 0-10, 0=most satisfied, 10=not satisfied at all) and whether the patients would recommend the surgical procedure to their friends or family. RESULTS: 1. Significant pain reduction three months postoperatively, NRS 4.5 to 2.2, (p=0.000). 2. Significant reduction of paraesthesia three months postoperatively from 84.8 to 24.2% (p=0.000) 3. Significant reduction of numbness three months postoperatively from 97% to 39% (p=0.000). 4. Significant improvement of sensitivity three months postoperatively from 91% no sensitivity to 28% no sensitivity (p=0.000). 5. Significant improvement of Hoffmann-Tinel sign three months postoperatively from 76% to 13% (p=0.000). 88 months postoperatively, we saw a significant pain reduction from an average preoperative pain level of NRS 4.5 to a postoperative pain level of 2.7 (p=0.048). 88 months postoperatively, 65% of the patients would recommend the surgical procedure to their family and friends, and patient satisfaction was high (NRS 3,4). CONCLUSION: Our long-term results show that Dellon's nerve decompression in the lower extremities leads to a marked, lasting pain reduction and a functional improvement.


Subject(s)
Decompression, Surgical , Postoperative Complications , Humans , Decompression, Surgical/methods , Male , Female , Middle Aged , Retrospective Studies , Aged , Postoperative Complications/etiology , Postoperative Complications/surgery , Follow-Up Studies , Diabetic Neuropathies/surgery , Adult , Pain Measurement , Polyneuropathies/surgery , Patient Satisfaction , Aged, 80 and over
7.
J Pers Med ; 14(2)2024 Feb 04.
Article in English | MEDLINE | ID: mdl-38392611

ABSTRACT

We report here a 46-year-old male patient with a 14 cm segmental bone defect of the radial shaft after third degree open infected fracture caused by a shrapnel injury. The patient underwent fixed-angle plate osteosynthesis and bone reconstruction of the radial shaft by a vascularized 3D-printed graft cage, including plastic coverage with a latissimus dorsi flap and an additional central vascular pedicle. Bony reconstruction of segmental defects still represents a major challenge in musculo-skeletal surgery. Thereby, 3D-printed scaffolds or graft cages display a new treatment option for bone restoration. As missing vascularization sets the limits for the treatment of large-volume bone defects by 3D-printed scaffolds, in the present case, we firstly describe the reconstruction of an extensive radial shaft bone defect by using a graft cage with additional vascularization.

8.
J Mech Behav Biomed Mater ; 152: 106433, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38316085

ABSTRACT

With fibrin-based vascular prostheses, vascular tissue engineering offers a promising approach for the fabrication of biologically active regenerative vascular grafts. As a potentially autologous biomaterial, fibrin exhibits excellent hemo- and biocompatibility. However, the major problem in the use of fibrin constructs in vascular tissue engineering, which has so far prevented their widespread clinical application, is the insufficient biomechanical stability of unprocessed fibrin matrices. In this proof-of-concept study, we investigated to what extent the addition of a spider silk network into the wall structure of fibrin-based vascular prostheses leads to an increase in biomechanical stability and an improvement in the biomimetic elastic behavior of the grafts. For the fabrication of hybrid prostheses composed of fibrin and spider silk, a statically cast tubular fibrin matrix was surrounded with an envelope layer of Trichonephila edulis silk using a custom built coiling machine. The fibrin matrix was then compacted and pressed into the spider silk network by transluminal balloon compression. This manufacturing process resulted in a hybrid prosthesis with a luminal diameter of 4 mm. Biomechanical characterization revealed a significant increase in biomechanical stability of spider silk reinforced grafts compared to exclusively compacted fibrin segments with a mean burst pressure of 362 ± 74 mmHg vs. 213 ± 14 mmHg (p < 0.05). Dynamic elastic behavior of the spider silk reinforced grafts was similar to native arteries. In addition, the coiling with spider silk allowed a significant increase in suture retention strength and resistance to external compression without compromising the endothelialization capacity of the grafts. Thus, spider silk reinforcement using the abluminal coiling technique represents an efficient and reproducible technique to optimize the biomechanical behavior of small-diameter fibrin-based vascular grafts.


Subject(s)
Blood Vessel Prosthesis , Silk , Sutures , Arteries , Fibrin
9.
J Appl Biomater Funct Mater ; 22: 22808000241226656, 2024.
Article in English | MEDLINE | ID: mdl-38253568

ABSTRACT

Human cartilage tissue remains a challenge for the development of therapeutic options due to its poor vascularization and reduced regenerative capacities. There are a variety of research approaches dealing with cartilage tissue engineering. In addition to different biomaterials, numerous cell populations have been investigated in bioreactor-supported experimental setups to improve cartilage tissue engineering. The concept of the present study was to investigate spider silk cocoons as scaffold seeded with adipose-derived stromal cells (ASC) in a custom-made bioreactor model using cyclic axial compression to engineer cartilage-like tissue. For chemical induction of differentiation, BMP-7 and TGF-ß2 were added and changes in cell morphology and de-novo tissue formation were investigated using histological staining to verify chondrogenic differentiation. By seeding spider silk cocoons with ASC, a high colonization density and cell proliferation could be achieved. Mechanical induction of differentiation using a newly established bioreactor model led to a more roundish cell phenotype and new extracellular matrix formation, indicating a chondrogenic differentiation. The addition of BMP-7 and TGF-ß2 enhanced the expression of cartilage specific markers in immunohistochemical staining. Overall, the present study can be seen as pilot study and valuable complementation to the published literature.


Subject(s)
Bone Morphogenetic Protein 7 , Transforming Growth Factor beta2 , Humans , Pilot Projects , Tissue Engineering , Cartilage , Bioreactors , Stromal Cells
10.
Ann Plast Surg ; 92(2): 212-221, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38170967

ABSTRACT

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.


Subject(s)
Diabetes Mellitus , Diabetic Neuropathies , Polyneuropathies , Humans , Leg , Diabetic Neuropathies/complications , Diabetic Neuropathies/surgery , Retrospective Studies , Hypesthesia/etiology , Hypesthesia/surgery , Lower Extremity/surgery , Lower Extremity/innervation , Pain/etiology , Polyneuropathies/surgery , Polyneuropathies/complications , Decompression, Surgical/methods , Treatment Outcome , Diabetes Mellitus/surgery
11.
JPRAS Open ; 39: 60-70, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38162534

ABSTRACT

Introduction: Chest contouring or subcutaneous mastectomy (SCM) in female-to-male (FtM) transgender individuals is the primary surgery in the gender reassignment process. Many authors report high rates of postoperative bleeding in these patients and discuss a possible influence of preoperative hormone therapy. However, there is a lack of data on the analysis between different surgical techniques and postoperative bleeding risk. Materials and Methods: In this retrospective study, we included 22 FtM transgender individuals who underwent bilateral SCM using 4 different techniques (44 breasts) between June 2014 and September 2023. Postoperative complications regarding surgical techniques and patient demographics were collected and analyzed. Results: SCM with free nipple grafting was the most commonly used technique (n = 12, 54.5%). The mean operative time was 163.4 ± 49.2 minutes. There were no significant differences in operative time between the surgical techniques (p ≥ 0.20 in all cases). The rate of acute postoperative bleeding was 20.5% (n = 9). Acute postoperative bleeding occurred most frequently in patients who received a semi-circular incision for SCM. There was no significant difference in the rate of acute postoperative bleeding between the different surgical techniques. BMI, breast weight, and duration of surgery were not associated with the rate of acute complications (p > 0.17 in all cases). Conclusions: Less invasive SCM techniques in FtM transgender individuals are associated with higher postoperative bleeding risk.

12.
Int Wound J ; 21(1): e14374, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37675770

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation , Infertility , Humans , Skin Transplantation/methods , Living Donors , Skin/microbiology
13.
PLoS One ; 18(11): e0291697, 2023.
Article in English | MEDLINE | ID: mdl-37967129

ABSTRACT

The reciprocal relationships between ecological process and landscape pattern are fundamental to landscape ecology. Landscape ecologists traditionally use raster maps portraying classified features such as land use or land cover categories, and metrics suggested by the patch-corridor-matrix conceptual model of pattern. Less attention has been given to the landscape gradient conceptual model and raster maps portraying numeric features such as greenness or percent vegetation cover. We introduce the open-source tool GraySpatCon to calculate and map a variety of landscape pattern metrics from both conceptual models using either categorical or numeric maps. The 51 metrics, drawn mostly from the landscape ecology and image processing literatures, are calculated from the frequencies of input pixel values and/or the pixel value adjacencies in an analysis region. GraySpatCon conducts either a moving window analysis which produces a continuous map of a pattern metric, or a global analysis which produces a single metric value. We describe an implementation in the GuidosToolbox desktop application which allows novice users to interactively explore GraySpatCon functionality. In the R desktop environment, we demonstrate several metrics using an example map of percent tree cover and illustrate a multi-scale moving window analysis to identify scale domains. Comparisons of computational efficiency indicate a substantial GraySpatCon advantage over related software in the R environment.


Subject(s)
Models, Theoretical , Software , Ecosystem , Conservation of Natural Resources
14.
J Clin Med ; 12(18)2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37762830

ABSTRACT

Traumatic finger injuries are very common in emergency medicine. When patients present with finger injuries, there is often damage to the vascular nerve bundles, which requires subsequent reconstruction. It is unknown if repairing a unilaterally injured artery affects patients' recovery in a well-perfused finger. This retrospective cohort study compares the clinical outcomes of 11 patients with one-vessel supply (mean age 48.3 years; 7 males, 4 females) to 14 patients with two-vessel supply (mean age 44.5 years; 8 males, 6 females). The patient outcomes were assessed using patient questionnaires (Disabilities of Arm, Shoulder, and Hand (DASH), European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L), and EuroQol visual analog scale (EQ-VAS)) and a clinical examination of hand function and imaging of circulatory efficiency. No significant changes were observed in the DASH, EQ-5D-5L, and EQ-VAS questionnaires. Clinical evaluation of hand function, measured by cold sensitivity, two-point discrimination, pain numerical analog scale, and grip strength also revealed no significant differences between cohorts. Blood flow measurements using thermal imaging revealed no effects on circulation in the affected digit. Collectively, the study finds reconstruction is not absolutely necessary when there is one intact digital artery as it is sufficient for healing and functional outcomes. We recommend finger artery reconstruction when both digital arteries are injured or if an immediate tension-free suture is possible.

15.
JPRAS Open ; 37: 34-41, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37693690

ABSTRACT

Background: E-cigarette abuse, also known as vaping, is a widespread habit. Recently, there have been increasing reports of explosions of these devices resulting in serious burn injuries, especially to the groin, hand, and face. Overheating rechargeable lithium-ion batteries are supposed to be the responsible mechanism, especially in low quality fabrications. Methods: In this single-center retrospective study, data of 46 patients are presented and analyzed. In addition to information on demographics, injury patterns, and treatment options, this is the first study investigating outcome after an average of 13 months via a standardized telephone interview of 31 patients (67%). Patients were specifically asked regarding their outcome, vaping habits, technical modifications to their devices and supply source. Results: Patients were mainly male (98.2%) with a median age of 36 years. Typical injury patterns included the groin region (n = 32; 69%), hands (n = 12; 25%) and face (n = 3; 7%). All patients underwent debridement, in nine cases hydrotherapeutically. 61% (n = 28) underwent consecutive tangential necrectomy and subsequent split thickness skin graft transplantation. Wound infection was observed in 18 patients (39%), with burn depth as a significant risk factor (p < 0.001). 91% of the followed-up patients were satisfied. Surprisingly, 38% were still using e-cigarettes. 42% (n = 13) reported manual modifications of their devices to prolong battery life or increasing smoke production. Conclusions: Injuries from exploding e-cigarettes can be serious and should be treated in a specialized burn center. E-cigarette explosions lead to characteristic injury patterns and often need surgical treatment. This should be made more public to reduce their use and keep people from modifying the devices. The counterintuitive and irrational observation of a high rate of abuse even after the injury underlines their addiction potential.

16.
Pathophysiology ; 30(3): 389-399, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37755396

ABSTRACT

In this article, we discuss a class of MYC-interacting lncRNAs (long non-coding RNAs) that share the following criteria: They are direct transcriptional targets of MYC. Their expression is coordinated with the expression of MYC. They are required for sustained MYC-driven cell proliferation, and they are not essential for cell survival. We refer to these lncRNAs as "MYC facilitators" and discuss two representative members of this class of lncRNAs, SNHG17 (small nuclear RNA host gene) and LNROP (long non-coding regulator of POU2F2). We also present a general hypothesis on the role of lncRNAs in MYC-mediated transcriptional regulation.

17.
Sci Rep ; 13(1): 12542, 2023 08 02.
Article in English | MEDLINE | ID: mdl-37532879

ABSTRACT

Flap surgery is a common treatment for severe wounds and a major determinant of surgical outcome. Flap survival and healing depends on adaptation of the local flap vasculature. Using a novel and defined model of fasciocutaneous flap surgery, we demonstrate that the Notch ligand Delta-like 1 (Dll1), expressed in vascular endothelial cells, regulates flap arteriogenesis, inflammation and flap survival. Utilizing the stereotyped anatomy of dorsal skin arteries, ligation of the major vascular pedicle induced strong collateral vessel development by end-to-end anastomosis in wildtype mice, which supported flap perfusion recovery over time. In mice with heterozygous deletion of Dll1, collateral vessel formation was strongly impaired, resulting in aberrant vascularization and subsequent necrosis of the tissue. Furthermore, Dll1 deficient mice showed severe inflammation in the flap dominated by monocytes and macrophages. This process is controlled by endothelial Dll1 in vivo, since the results were recapitulated in mice with endothelial-specific deletion of Dll1. Thus, our model provides a platform to study vascular adaptation to flap surgery and molecular and cellular regulators influencing flap healing and survival.


Subject(s)
Endothelial Cells , Neovascularization, Physiologic , Mice , Animals , Neovascularization, Physiologic/physiology , Calcium-Binding Proteins/genetics , Wound Healing , Inflammation
18.
Proc Natl Acad Sci U S A ; 120(34): e2304071120, 2023 08 22.
Article in English | MEDLINE | ID: mdl-37585458

ABSTRACT

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.


Subject(s)
Phosphatidylinositol 3-Kinase , Phosphatidylinositol 3-Kinases , Humans , Phosphatidylinositol 3-Kinases/metabolism , Ligands , Cryoelectron Microscopy , Adenosine Triphosphate/metabolism
19.
Biochim Biophys Acta Rev Cancer ; 1878(5): 188947, 2023 09.
Article in English | MEDLINE | ID: mdl-37394020

ABSTRACT

Recent cryo-electron microscopic (cryo-EM) investigations have succeeded in the analysis of various structural conformations and functional states of PI3Kα, a dimer consisting of the catalytic subunit p110α and the regulatory subunit p85α of class IA of phosphoinositide 3-kinase. High resolution structures have been obtained of the unliganded and of BYL-719-bound PI3Kα. The latter provides information on excessively flexible domains of p85α that are then further analyzed with nanobodies and CXMS (chemical cross-linking, digestion and mass spectrometry). Analysis of p110α helical and kinase domain mutations reveals mutant-specific features that can be linked to the gain of function in enzymatic and signaling activities.


Subject(s)
Phosphatidylinositol 3-Kinase , Phosphatidylinositol 3-Kinases , Humans , Phosphatidylinositol 3-Kinases/metabolism , Cryoelectron Microscopy , Mutation , Catalytic Domain/genetics
20.
JPRAS Open ; 37: 1-8, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37288428

ABSTRACT

Background: Acquired factor XIII deficiency is an underestimated risk in patients with large surface burns, which potentially exposes these patients to prolonged bleeding and delayed wound healing if undetected. Methods: A retrospective matched-pair analysis of the burn registry of the Department of Plastic, Aesthetic, Hand, and Reconstructive Surgery of Hannover Medical School was performed from 2018 to 2023. Results: A total of 18 patients were included. Acquired factor XIII deficiency was not statistically significant correlated with age, sex, or body mass index. Patients who developed acquired factor XIII deficiency had a significantly longer hospital stay (72.8 days) compared with those in the matched group (46.4 days), although burn depths, total body surface area, and Abbreviated Burn Severity Index were not statistically correlated with factor XIII deficiency. Conclusions: Little is known about acquired factor XIII deficiency in patients with burns. Factor XIII supplementation may improve hemostasis, wound healing, and general outcome while reducing the patient's exposure to blood products.

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