Skin Soft Tissue Research Articles

PDGFB RNA in situ hybridization for the diagnosis of dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a spindle cell neoplasm of the skin and superficial soft tissue with a tendency for locally aggressive behavior; metastatic potential coincides with fibrosarcomatous transformation. The vast majority of DFSPs harbor the t(17;22) translocation resulting in a COL1A1-PDGFB fusion that drives autocrine growth stimulation via PDGFB overexpression. Here, we examined the utility of PDGFB RNA chromogenic in situ hybridization (CISH) for the diagnosis of DFSP. A total of 337 tumors represented in whole tissue sections and tissue microarrays, including 37 cases of DFSP and 300 histologically similar spindle cell tumors, were subjected to PDGFB RNA CISH using commercially available probes. PDGFB overexpression was observed by light microscopy in 24 of 26 conventional DFSPs (92%) and 11 of 11 fibrosarcomatous DFSPs (100%). One of two DFSPs negative for PDGFB by RNA CISH was found to harbor an uncommon alternative rearrangement involving PDGFD. All examined cases of histologic mimics were negative for PDGFB overexpression; limited PDGFB expression, not reaching an empirical threshold of greater than 5 puncta or one aggregate of chromogen in more than 25% of cells, was observed in 7 of 300 mimics (2.3%), including desmoplastic melanoma, malignant peripheral nerve sheath tumor, angiosarcoma, and pleomorphic dermal sarcoma. Vascular PDGFB expression was seen in several tumor types. We conclude that PDGFB RNA CISH, with careful interpretation and the use of appropriate thresholds, may serve as a surrogate marker of PDGFB rearrangement and a useful ancillary tool for the diagnosis of DFSP.

Pay attention to the prevention and treatment of iatrogenic wound

The iatrogenic wound is defined as infection, necrosis, or defect of the skin and deep soft tissue resulting from a medical procedure. At present, the main factors causing iatrogenic wounds include surgery, radiotherapy, interventional therapy, and drugs etc. Iatrogenic wounds are attributed to iatrogenic injuries that are in accordance with ethics, laws, and relevant regulations, and the degree of these injuries is within an acceptable range. Medical staff can reduce the incidence of iatrogenic wounds and the degree of injury by improving medical technology and responsibility in medical procedures. Iatrogenic wounds can be repaired and the patient's physical and mental health can be restored with targeted medical treatment. How to effectively prevent and treat iatrogenic wounds so as to minimize the degree of iatrogenic injuries to patients needs further exploration. To sum up, the purpose to publish this special topic in this issue is to arouse the peer's attention to the prevention and treatment of iatrogenic wounds.

3D Printed Multi-material Medical Phantoms for Needle-tissue Interaction Modelling of Heterogeneous Structures

The fabrication of multi-material medical phantoms with both patient-specificity and realistic mechanical properties is of great importance for the development of surgical planning and medical training. In this work, a 3D multi-material printing system for medical phantom manufacturing was developed. Rigid and elastomeric materials are firstly combined in such application for an accurate tactile feedback. The phantom is designed with multiple layers, where silicone ink, Thermoplastic Polyurethane (TPU), and Acrylonitrile Butadiene Styrene (ABS) were chosen as printing materials for skin, soft tissue, and bone, respectively. Then, the printed phantoms were utilized for the investigation of needle-phantom interaction by needle insertion experiments. The mechanical needle-phantom interaction was characterized by skin-soft tissue interfacial puncture force, puncture depth, and number of insertion force peaks. The experiments demonstrated that the manufacturing conditions, i.e. the silicone grease ratio, interfacial thickness and the infill rate, played effective roles in regulating mechanical needle-phantom interaction. Moreover, the influences of material properties, including interfacial thickness and ultimate stress, on needle-phantom interaction were studied by finite element simulation. Also, a patient-specific forearm phantom was printed, where the anatomical features were acquired from Computed Tomography (CT) data. This study provided a potential manufacturing method for multi-material medical phantoms with tunable mechanical properties and offered guidelines for better phantom design.

Optimization of the Soft Tissue Envelope of the Nose in Rhinoplasty Utilizing Fat Transfer Combined with Platelet-Rich Fibrin.

A thin or damaged skin soft tissue envelope may cause concerns in primary and secondary rhinoplasty. During postoperative healing, unpredictable scarring and contraction may occur and lead to significant aesthetic and trophic sequelae. Besides a meticulous surgical technique, there are no reliable techniques to prevent long-term skin damage and shrinkage. Fat transfer with addition of platelet-rich fibrin (PRF) harbors the possibility of local soft tissue regeneration and skin rejuvenation through growth factors and mesenchymal stem cells. It may also facilitate the creation of a thin fat layer on the dorsum to prevent shrink-wrap forces and conceal small irregularities. The goal is to provide evidence for the feasibility, durability, and beneficial effect of diced macrofat transfer bonded with PRF on the nasal dorsum. We present the technique of fat transfer conjugated with PRF as a nasal dorsal graft. Clinical endpoints were the prevention of trophic disturbances and atrophy at a 1-year postoperative follow-up. We present the skin mobility test as a clinical indicator of a healthy soft tissue envelope. The presented case series consists of 107 rhinoplasties. Fat was harvested in the umbilical or costal region. PRF was created by centrifugation of autologous whole blood samples. Macrofat was diced, cleaned, and bonded with PRF. The compound transplants were transferred to the nasal dorsum. There were no perioperative complications or wound-healing issues. Mean follow-up was 14 months. Clinical inspection showed good skin quality and no signs of shrinkage, marked scarring, or color changes with positive skin mobility test in all patients. Survival of fat was confirmed by ultrasonography and magnetic resonance imaging. Diced macrofat transfer in conjunction with PRF to the nasal dorsum is a feasible and safe method. A beneficial effect on the soft tissue envelope is demonstrated as well as the prevention of shrink-wrap forces.

Systematic Review: Adipose-Derived Mesenchymal Stem Cells, Platelet-Rich Plasma and Biomaterials as New Regenerative Strategies in Chronic Skin Wounds and Soft Tissue Defects.

The number of clinical trials evaluating adipose-derived mesenchymal stem cells (AD-MSCs), platelet-rich plasma (PRP), and biomaterials efficacy in regenerative plastic surgery has exponentially increased during the last ten years. AD-MSCs are easily accessible from various fat depots and show intrinsic plasticity in giving rise to cell types involved in wound healing and angiogenesis. AD-MSCs have been used in the treatment of soft tissue defects and chronic wounds, employed in conjunction with a fat grafting technique or with dermal substitute scaffolds and platelet-rich plasma. In this systematic review, an overview of the current knowledge on this topic has been provided, based on existing studies and the authors’ experience. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, PRP, and biomaterials used in soft tissue defects and chronic wounds. Of the 2136 articles initially identified, 422 articles focusing on regenerative strategies in wound healing were selected and, consequently, only 278 articles apparently related to AD-MSC, PRP, and biomaterials were initially assessed for eligibility. Of these, 85 articles were excluded as pre-clinical, experimental, and in vitro studies. For the above-mentioned reasons, 193 articles were selected; of this amount, 121 letters, expert opinions, commentary, and editorials were removed. The remaining 72 articles, strictly regarding the use of AD-MSCs, PRP, and biomaterials in chronic skin wounds and soft tissue defects, were analyzed. The studies included had to match predetermined criteria according to the patients, intervention, comparator, outcomes, and study design (PICOS) approach. The information analyzed highlights the safety and efficacy of AD-MSCs, PRP, and biomaterials on soft tissue defects and chronic wounds, without major side effects.

Mono vs. combo regimens with novel beta-lactam/beta-lactamase inhibitor combinations for the treatment of infections due to carbapenemase-producing Enterobacterales: insights from the literature.

Ceftazidime-avibactam (CZA), meropenem-vaborbactam (MVB) and imipenem-relebactam (I-R) are combinations of old ß-lactams with novel non-ß-lactam ß-lactamase inhibitors (BLBLIs) able to inhibit some carbapenemases, such as the KPC-type, thus are becoming the standard for difficult-to-treat carbapenemase-producing Enterobacterales (CPE); a practical question is whether these novel BLBLIs should be used as monotherapy or as part of a combination regimen with other antibiotics, and if so, with which ones, to reduce the emergence of resistant strains and to optimize their efficacy. In this short review, we assessed clinical outcomes in patients with CPE-infections treated with the novel BLBLIs as mono- or combo-regimens, and laboratory studies on the synergistic effects with other antimicrobials. Available evidence on combination therapy is scarce and mainly limited to retrospective studies involving 630 patients treated with CZA: aminoglycosides were used in 39.6% of 336 patientstreated with combo-regimens, followed by polymyxin B/colistin (24.4%), tigecycline (24.1%), carbapenems (13.4%) and fosfomycin (5.4%). Aminoglycosides could be useful in case of bloodstream and severe urinary infections. Pneumonia is a risk factor for CZA-resistance emergence: fosfomycin, due to favorable lung pharmacokinetics/pharmacodynamics, could represent an interesting partner; fosfomycin could be added alsofor osteomyelitis. Tigecycline could be preferred for intrabdominal and skin-soft tissue infections. Due to nephrotoxicity and lack of in vitro synergy, the association CZA/colistin seems not optimal. MVB and I-R were mostly used as monotherapies. Currently, there is no definitive evidence whether combinations are more effective than monotherapies; further studies are warranted, and to date only personal opinions can be provided.

How I do it: minimizing muscle damage in microvascular decompression for hemifacial spasm.

Key hole surgery was recruited for MVD surgery since the maneuver is through the small space between the cerebellum and temporal/occipital bone. However, even small wounds can cause severe postoperative pain if there is significant tissue damage. Attention has been given to the size of the craniotomy rather than to the skin incision or soft tissues such as muscles. Suboccipital muscle dissection focusing on splitting the splenius capitis muscle was presented. The dura was reapproximated without additional dissection to harvest a fascia graft. Muscle injury should be minimized to alleviate postoperative pain.

Multi-tissue layering and path planning of in situ bioprinting for complex skin and soft tissue defects

Purpose Reconstructing multi-layer tissue structure using cell printing to repairing complex tissue defect is a challenging task, especially using in situ bioprinting. This study aims to propose a method of in situ bioprinting multi-tissue layering and path planning for complex skin and soft tissue defects. Design/methodology/approach The scanned three-dimensional (3D) point cloud of the skin and soft tissue defect is taken as the input data, the depth value of the defect is then calculated using a two-step grid division method, and the tissue layer is judged according to the depth value. Then, the surface layering and path planning in the normal direction are performed for different tissue layers to achieve precise tissue layering filling of complex skin soft tissue defects. Findings The two-step grid method can accurately calculate the depth of skin and soft tissue defects and judge the tissue layer accordingly. In the in situ bioprinting experiment of the defect model, the defect can be completely closed. The defect can be reconstructed in situ, and the reconstructed structure is basically the same as the original skin tissue structure, proving the feasibility of the proposed method. Originality/value This study proposes an in situ bioprinting multi-tissue layering and path planning method for complex skin and soft tissue defects, which can directly convert the scanned 3D point cloud into a multi-tissue in situ bioprinting path. The printed result has a similar structure to that of the original skin tissue, which can make cells or growth factors act on the corresponding tissue layer targets.

SKIN AND SUBCUTANEOUS ADIPOSE TISSUE DAMAGE AFTER RADIATION THERAPY IN BREAST CANCER PATIENTS.

The analysis of long-term researches of the pathological changes arising in soft tissues at patients with a breast cancer as a result of radical surgical treatment and adjuvant radiotherapy is carried out in work. The article shows that the standard approach to postoperative radiation therapy, which is based only on the prevalence of the primary tumor process is not always justified. Very often it leads to excessive radiation load on the patient's body and the development of local acute and chronic radiation reactions of the skin, subcutaneous tissue and other soft tissues.In this regard, the question of differentiated purpose of radiotherapy acquires special value first of all at patients with small primary prevalence of tumor process. The paper presents the results of studies to study changes in the anterior chest wall in patients with breast cancer. In relation to the conduct of adjuvant radiotherapy more often need to use the concept of personalized radiation therapy. Radical operation, post-radiation early and late pathological changes in soft tissues, disturbance of microcirculation of lymph and blood, disturbance of innervation of vessels of an upper extremity, peripheral nerves in system of a cervical and plexus plexus, leads to intensive degen-erative and dystrophic changes in soft tissues of the upper. and causes morphological changes in them and further progression of reflex neurovascular and neurodystrophic disorders. Based on the data of adverse effects of radio-therapy on the skin and surrounding tissues, as well as to reduce excessive radiation exposure to the patient's body, a differentiated approach to the appointment of adjuvant radiation therapy.

Mini-inciziona tehnika u zbrinjavanju sindroma karpalnog tunela

Introduction/Aim: Carpal tunnel syndrome (CST) is the most common cause of upper extremity compressive neuropathy. Until the introduction of endoscopy, the dominant surgical method was classic open surgery. The objective of the paper is to examine the efficacy, safety and economic value of the mini-open carpal tunnel release technique using a longitudinal 2 cm long incision in the carpal region. Methods: The diagnosis was made based on clinical examination, followed by an ENMG. The study includes only patients with idiopathic CTS, while those who have developed CTS as a result of secondary causes have been excluded from the study. All patients were operated on under local anaesthesia, WALANT, without the use of a tourniquet. A longitudinal incision 2 cm long is made in the line of the radial edge of the ring finger, 2-3 cm distal to the wrist flexion crease, immediately proximal of the Caplan cardinal line and ulnar to the thenar crease. Upon cutting through the skin and subcutaneous soft tissue, the superficial fascia is identified and then cut with the same scalpel in the same direction and the same length. The transversal ligament is then identified and carefully incised with a scalpel enough to allow further decompression with the use of scissors. Using standard surgical scissors for the hand, the ligament is cut proximally to the forearm fascia and then distally until a faint crackling sound is heard, which means that the ligament had been completely cut. This must be checked by inserting the Freer elevator proximally and distally to the edge of the ligament. Now it is possible to identify the nerve and accompanying hand flexor tendons. Sutures are placed only on the skin and a roll of gauze is fixed to the wound with an elastic bandage to provide compression. The first check-up is on the very next day and the patient is advised to start doing hand exercises. The sutures are removed 10-14 days after surgery. Results: From January 2018 to December 2019, 35 carpal tunnel decompressions were performed on 30 patients using the mini-open decompression technique and standard surgical scissors. The surgery was performed on 22 patients in the operating room and 8 patients in the infirmary. There were no intraoperative complications. All patients reported no night pain from the very first day after surgery. Pillar pain, incision pain and hand weakness were progressively becoming less pronounced during the next 12 weeks. At the final check-up, only one patient still had pronounced symptoms that required a reintervention. The rest of the patients had completely recovered. Even though the endoscopic procedure for carpal tunnel decompression is constantly evolving, the classic open method and newly developed mini-open carpal tunnel release technique remain the treatments of choice. Conclusion: Our research shows that the mini-open carpal tunnel release technique is a quick, efficient, safe and cheap surgical technique for treating carpal tunnel compressive neuropathy.

The modified TIME-H scoring system, a versatile tool in wound management practice: a preliminary report.

Background and Aims:The concept of WBP (wound bed preparation) has revolutionized the way to diagnose and correctly identify the best therapeutic path about the widespread clinical problem of difficult wounds. Starting from the modified TIME-H, authors conducted a preliminary study with the aim of assessing the impact of skin lesions and soft tissues for the surgical patient.Materials and Methods:38 patients were preliminarily evaluated. The patients were classified according to the lesion examined, in particular among those who had an infectious or vascular etiology (SSTIs), and patients with surgical site lesions (SSI) and assigned to one of three categories prognosis: favorable (with healing expected within 12 weeks) (0-3A, 0-1B), intermediate (with healing expected over 12 weeks) (4-6A, 2-4B) and uncertain healing (7-8A, 5-8B).Results:At the end of the one-year observation period, authors established the healing prediction rate among the studied lesions: the surgical site lesions presented the highest percentage of predictivity (88%), followed by the mixed etiology (72%) and the infectious/vascular injuries (63%).Conclusion:This modified-TIME-H can be considered as a versatile and useful scoring tool that should be used in daily clinical practice for the study and treatment of chronic wound diseases.

Metastases to the Stomach: Clinicopathologic Features of Metastases Mimicking Gastric Primaries.

Metastatic involvement of the stomach is a rare event. Our aim in this study was to document the clinicopathological findings in patients with gastric metastases and find out if there are any potentially significant features to be used in the differential diagnosis. Our cohort consisted of 17 histologically verified gastric metastasis cases. Clinical, endoscopic and microscopic features were retrospectively analyzed. The primary sites were the breast, skin, lungs, ovaries, colon, and gluteal soft tissue. Three patients were symptomatic because of the metastatic involvement of the stomach and 9 patients had concomitant metastasis in other sites. Invasive lobular breast carcinoma and malignant melanoma were the most common metastatic malignancies. The most common macroscopic appearance was the diffuse infiltrative type (Borrmann Type 4). Most of the metastatic lesions endoscopically mimicked primary gastric cancer. Furthermore, some of the metastatic lesions, particularly invasive lobular carcinoma of the breast and malignant melanoma, displayed histopathologic features similar to the primary gastric malignancies to a certain extent. The possibility of metastatic involvement of stomach must be kept in mind while dealing with a gastric mass lesion in a cancer patient, even though the clinical and endoscopic features suggest primary gastric cancer. Our study points out the importance of conveying the information about medical history and clinical findings of the patients for correct pathologic differential diagnosis.

Extensive Extranodal Involvement in a case of Non-Hodgkin's Lymphoma with sparing of lymph nodes and lymphatic organs.

Non-Hodgkin lymphoma (NHL) is a group of malignant lymphoproliferative disorders arising predominantly in the lymph nodes with various clinical and histological characteristics. At least 25% of NHL originates from tissues other than lymph nodes and sometimes even from sites that do not contain lymphoid tissue. These are referred to as primary extranodal lymphomas (pENLs). pENL is a universal diagnostic challenge to the clinicians and pathologists due to their varied clinical presentations, morphological mimicry, and molecular alterations. The GIT is the most common site of pENL followed by nasopharynx/oropharynx, testis, uterus/ovary, thyroid, and central nervous system. Long bones (tibia), maxillary sinus, skin, and paraspinal soft tissues are the other rare anatomic sites of pENL. We reported a case of a 60-year-old female presented with pain and mass in the pelvis region. 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and fused PET/CT was done, which revealed extensive extranodal involvement of the lung, bilateral kidneys, uterus, ovaries, bones, and muscles with no involvement of lymph nodes or lymphomatous organs. Extensive extranodal involvement with sparing of lymphomatous organ has not been reported earlier.

Standardization and Wound-Healing Activity of Petroleum, Ethanolic and Aqueous Extracts of Ficus Benghalensis Leaves

Wound healing is the repair process of injury on the skin and other soft tissues. After injury, an inflammatory response occurs and tissue cells below the dermis begin to increase collagen formation. Later, the epithelial tissue is regenerated. There are three stages of wound healing process: inflammation, proliferation and remodeling. Traditionally, Ficus benghalensis plant has been used for wound healing but no clear scientific data are available related to this activity. The present work was designed to explore the wound-healing efficacy of petroleum, ethanolic and aqueous extracts of F. benghalensis leaves as evaluated on excision wound models. These leaves extracts were studied for their phytochemicals by means of different chemical tests. Parameters studied include the rate of wound contraction and period of complete epithelialization of incision wound. Student’s t-test was used to analyze the results obtained from this study and confidence level P < 0.05 was considered significant. All the petroleum, ethanolic and aqueous extracts of F. benghalensis leaves were found to possess significant wound-healing activity, which was evidenced by decrease in the period of epithelialization and increase in the rate of wound contraction. The obtained results showed that all extracts of F. benghalensis leaves were capable of accelerated wound-healing activity comparable with a control drug.

A Soft Tissue Acupuncture Model Based on Mass-Spring Force Net

In the simulation of acupuncture manipulation, it is necessary to accurately capture the information of acupuncture points and particles around them. Therefore, a soft tissue modeling method that can accurately track model particles is needed. In this paper, a soft tissue acupuncture model based on the mass-spring force net is designed. MSM is used as the auxiliary model and the SHF model is combined. SHF is used to establish a three-layer soft tissue model of skin, fat, and muscle, and a layer of the MSM based force network is covered on the surface of soft tissue to realize the complementary advantages and disadvantages of spherical harmonic function and MSM. In addition, a springback algorithm is designed to simulate the springback phenomenon of soft tissue skin during acupuncture. The evaluation results show that the soft tissue acupuncture modeling method based on mass-spring force net can effectively simulate the springback phenomenon of soft tissue surface during acupuncture surgery, and has good comprehensive performance in the application of virtual acupuncture surgery simulation.

89. A Collaborative &amp; Novel Antimicrobial Stewardship Initiative– Mandatory Approval of Peripherally Inserted Central Venous Catheters

BackgroundCentral line-associated bloodstream infections result in thousands of deaths and billions of dollars annually. At the Augusta University Medical Center (AUMC), it was identified that ~50% of peripherally inserted central venous catheters (PICCs) that were placed for intravenous (IV) antibiotic administration were unnecessary. A novel initiative was implemented, which required antimicrobial stewardship/infectious diseases approval for PICC insertions if the indication was for IV antibiotic administration only. The objective of this study was to determine the impact of this initiative.MethodsA retrospective observational study was conducted at the AUMC. All adult patients with a PICC line insertion order for IV antibiotic administration, between December 2017 and May 2019 were included. The vascular access team would forward requests for PICC insertions to the antimicrobial stewardship pharmacist. The pharmacist would approve/disapprove the PICC or recommend an infectious diseases consult. The variables collected were: infection types, infectious diseases consultation, reason for PICC denial and 30-day PICC-related complications.ResultsA total of 215 requests for PICC insertion (for IV antibiotics) were placed. Of these, 54% of the requests were denied, while 46% were approved. The reasons for PICC denial included: midline catheter preferred (47%), switched to oral antibiotics (33%), further work-up required (10%), or no antibiotics needed (7%). The types of infections treated were: bone and joint infections (28%), urinary tract infections (13%), intra-abdominal infections (12%), endocarditis/endovascular infections (11%), skin soft tissue infections (9%), pneumonia (7%), catheter-related bloodstream infections (6%), central nervous system infections (6%), bacteremia (4%) and others (4%).The infectious diseases consult team was involved in the care of 79% of the patients. Of those that received a PICC line, only 5% experienced any PICC-related complications. The overall cost savings for PICCs that were denied was ~ $294,000.ConclusionMandatory antimicrobial stewardship/infectious diseases approval for PICC insertion can decrease healthcare cost and reduce the number of unnecessary PICC lines placed.Disclosures All Authors: No reported disclosures

Radiologic Findings of Complicated Alloplastic Implants in the Nasal Dorsum.

ObjectivesWhen performing cosmetic rhinoplasty with alloplastic materials, complications such as implant visualization, inflammation, dislocation, and extrusion should be thoroughly evaluated. Although computed tomography (CT) can provide useful information about the implant status and its interaction with the skin soft tissue envelope (SSTE), the radiologic findings of these interactions have rarely been reported.MethodsWe retrospectively reviewed the data of 80 patients who underwent facial bone CT or ostiomeatal unit CT at Asan Medical Center between July 2008 and January 2020 for the evaluation of dorsal implants with complications. We reviewed the implantation period, implant dislocation, implant curling or deformation, radiodensity (in Hounsfield units), and nasal bone changes including bone erosion or hyperostosis.ResultsOf the 80 patients, 67 (83.8%) had silicone implants and 13 (16.2%) had Gore-Tex implants. The radiologic findings of the silicone implants were as follows: maintenance of the implant shape (80.6%), radiolucency (similar density to that of fat tissue) halo (83.6%), and homogeneous attenuation (82.1%). Peri-implant calcification was often found in silicone implants with >20-year implantation periods. The findings of Gore-Tex were as follows: curling or deformation (84.6%), heterogeneous attenuation (84.6%), and consistent peri-implant calcification over time.ConclusionSilicone and Gore-Tex implants have distinctive radiologic features. These findings of alloplastic materials help us to understand how implants behave in the nasal dorsum and how they affect the SSTE.

Immune Checkpoint Markers in Superficial Angiosarcomas: PD-L1, PD-1, CD8, LAG-3, and Tumor-Infiltrating Lymphocytes.

Cutaneous angiosarcomas may express programmed death ligand-1 (PD-L1) and PD-L1 expression, and the presence of tumor-infiltrating lymphocytes (TILs) correlates with outcome. These observations provide a basis for PD-1/PD-L1 inhibitor therapy. Lymphocyte activation gene 3 (LAG-3) is an inhibitory receptor that interacts with the PD-L1 axis and is considered to be a marker of immune exhaustion. The presence of LAG-3-positive lymphocytes in cutaneous angiosarcoma has not been established. We reviewed 10 cases of treatment naive angiosarcoma of skin and superficial soft tissue and assessed for PD-L1 (ZR3) expression, presence of TILs, and expression of CD8, PD1, and LAG-3 by tumor-associated inflammatory cells by immunohistochemistry. All 10 angiosarcomas were positive for PD-L1: 7 with high expression and 3 with low expression. TILs were present in all tumors: brisk in 7 and nonbrisk in 3. CD8 lymphocytes were present in all tumors with a range of 212-1274 cells per square millimeter (mean 557 CD8 cells/mm2). LAG-3-positive lymphocytes were present in 9 of 10 angiosarcomas with a range of 0-728 cells/mm2 (mean 146 LAG-3 cells cells/mm2). The ratio of LAG-3 lymphocytes to CD8 lymphocytes was 0%-59% (mean 27%). The PD1 cell counts were intermediate between CD8 and LAG3 counts. Cutaneous angiosarcomas frequently express PD-L1, have prominent numbers of CD8 positive, and have smaller numbers of LAG-3-positive and PD-1-positive TILs. Our findings provide further evidence of PD-L1 expression in cutaneous angiosarcoma and the promise for immune checkpoint inhibitor therapy.

An Emerging Infection: Streptococcal Toxic Shock-Like Syndrome Caused By Group B Streptococcus (GBS), Streptococcus Agalactiae

Abstract Introduction/Objective Streptococcus agalactiae, Group B Streptococcus (GBS), is a major cause of neonatal sepsis and infections in pregnant women. However, incidence of invasive GBS infections has more than doubled in the last two decades with highest risk in adults 65 years or older. Other risk factors are diabetes, malignancy, and immunocompromised state. Bacteremia and skin soft tissue infections are the most common invasive infections in nonpregnant adults. Rarely GBS infection has a fulminating pyrogenic exotoxin-mediated course characterized by acute onset, multiorgan failure, shock, and sometimes death, referred to as toxic shock-like syndrome. Methods A 77-year-old hypertensive female with uncontrolled type 2 diabetes mellitus and a history of bilateral foot ulcers presented to the hospital in probable septic shock. Clinical diagnosis of necrotizing fasciitis was made and she underwent bilateral lower limb amputations. Results Grossly soft tissue appeared gray. Microscopically fascia was necrotic without neutrophils present and Gram stain revealed sheets of Gram positive cocci. These findings reflected histopathologic Stage III necrotizing fasciitis, which is associated with 47% mortality. Autopsy showed a similar histology of Stage III necrotizing fasciitis involving the surgical stump. Erythema and desquamation of the upper limbs bilaterally and multi-organ failure met the clinical picture of Streptococcal Toxic Shock Syndrome (STSS) and fulfilled the criteria for TSS due to Group A Streptococcus (GAS), defined by The Working Group on Severe Streptococcal Infections. Conclusion Group B Streptococcal Toxic Shock-Like Syndrome may have a similar outcome to STSS caused by GAS and other pathogens and, in limited studies, mortality has been 30% or greater.

Classic Ehlers\u2013Dalnos syndrome presenting as atypical chronic haematoma: a case report with novel frameshift mutation in COL5A1

BackgroundEhlers–Danlos syndrome (EDS) is a group of inherited connective tissue disorders characterized by skin hyperextensibility, joint hypermobility and soft tissue vulnerable to blunt injury. Early recognition and diagnosis are crucial to patients to provide appropriate treatment, as well as to screen for life-threatening conditions such as aortic dissection and hollow organ perforation. The diagnosis of EDS is made based on clinical presentations, skin biopsy, and electron microscopy findings. To date, mutations in at least 20 genes have been found to cause the Ehlers-Danlos syndromes. However, EDS is still underestimated due to lack of awareness of its variable clinical presentations. Here we reported an EDS case with atypical initial presentation and a novel genetic mutation.Case presentationThis 4-year-old Taiwanese male patient presented with easy bruising, multiple ecchymoses, joint hypermobility, hyperextensible skin, and prolonged pretibial haematoma. He was initially suspected of a bleeding tendency due to coagulation disorders. The coagulation test results were normal. DNA sequencing was performed for molecular diagnosis. Subsequently, the diagnosis of classical EDS was made by identifying a novel frameshift mutation in COL5A1 [NM_000093.4:c.4211_4212delAG, p.Gln1404Arg]. This mutation in the type V collagen gene COL5A1 contributes to the phenotype of classical EDS. This novel frameshift mutation may disturb the structural stability of collagen V and interfere with its heparin binding capacity, explaining the chronic haematoma.ConclusionThe reported case showed the unusual features of chronic haematoma. This novel frameshift mutation and its phenotype correlation can provide useful information for practitioners about early recognition in Ehlers–Danlos syndrome.