Long-Term Safety of Facilitated Subcutaneous Immunoglobulin 10% Treatment in US Clinical Practice in Patients with Primary Immunodeficiency Diseases: Results from a Post-Authorization Safety Study.

Facilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that utilizes recombinant human hyaluronidase (rHuPH20) to enhance immunoglobulin dispersion and absorption, allowing for longer treatment intervals similar to intravenous immunoglobulin (up to once monthly). fSCIG 10% is indicated in the USA for treating adults and children aged ≥ 2 years with primary immunodeficiency diseases (PIDs). This prospective, non-interventional, open-label, multicenter, post-authorization safety study (NCT02593188) was conducted in the USA from November 2015 to October 2021 to assess the long-term safety of fSCIG 10% in routine clinical practice. Patients with PIDs aged ≥ 16 years who were prescribed and/or had started fSCIG 10% treatment were enrolled. In total, 253 patients were enrolled and included (full analysis set). Participants received fSCIG 10% treatment for a median (interquartile range) of 10.0 (3.5-11.8) months, with the majority of infusions administered every 4 weeks (54.4% [1197/2201 infusions]) and at home (62.6% [1395/2230 infusions]). Overall, 98.5% of infusions were administered without rate reduction, interruption, or discontinuation due to adverse events (AEs). Treatment-related, non-serious AEs were experienced by 52 patients (20.6%, 284 events). Two patients (0.8%) each experienced one treatment-related serious AE (aseptic meningitis and deep vein thrombosis). Development of antibodies against rHuPH20 was uncommon; 14/196 patients (7.1%) tested positive for binding antibodies (titer ≥ 1:160) with no neutralizing antibodies detected. There was no relationship between anti-rHuPH20 antibody positivity and the occurrence of treatment-related serious or non-serious AEs. Long-term, repeated self-administration of fSCIG 10% was well tolerated in US clinical practice by patients with PIDs.

Late Facial Edema After Lip Filling With Hyaluronic Acid: Possible Association With the Use of Ozempic.

In recent years there has been an extraordinary increase in the use of different filler materials as facial cosmetic treatments. The popularity of injectable tissue fillers among individuals who wish to restore volume and gain a more youthful appearance is because it is a minimally invasive esthetic procedure for soft tissue augmentation. However, although they are considered efficient and safe, they can trigger complications such as swelling, bruising, erythema, pain, infection, nodule formation, vascular occlusion, and pigmentary changes. The objective of this article was to present a case of a 46-year-old patient who presented with significant facial edema 3 months after lip and infraorbital filling with hyaluronic acid, resistant to medication, which appeared and worsened after starting to use Ozempic for weight loss. Therefore, we chose to perform an intralesional application of hyaluronidase 2.000utr, immediately observing the decrease in edema. After a week, the patient was completely recovered, with no signs of edema, no allergic reactions and feeling very well. The etiology of late inflammatory reactions is unclear and we believe that some medications may be capable of initiating these immune responses. Hyaluronidase is an effective treatment to reverse adverse reactions from hyaluronic acid injection, dissolving the peptide bond proteins within the hyaluronic acid, increasing the viscosity of the material and allowing it to be dispersed throughout the soft tissue.

Efficacy of Superselective Intra-arterial Recanalization of Embolized Arteries Resulting from Facial Hyaluronic Acid Injection.

BACKGROUND: Arterial embolism is a rare complication caused by hyaluronic acid (HA) injection. However, it is one of the most serious complications. Once it happens, the complication would have a great and long-term impact on patients. Intra-arterial recanalization has been reported for recovering the visual acuity in patients with visual loss caused by hyaluronic acid. There is little report about the benefits of superselective intra-arterial recanalization therapy for skin wounds caused by hyaluronic acid vascular embolization. METHODS: Eight patients who had received the superselective intra-arterial recanalization therapy were retrospectively reviewed. Hyaluronidase was injected into the facial artery by superselective intra-arterial recanalization therapy, followed by symptomatic treatment. The facial artery recanalization was successfully performed and no interventional procedure-related adverse events happened. RESULTS: Arterial embolization accompanies by the interruption or reduction of blood supply, followed by ochrodermia, pain, numbness, swelling, yellowish white secreta and even necrosis on skin wound area. Early detection of skin blood supply disorders and early recovery of blood supply are very critical to treat facial artery embolization caused by HA. After superselective intra-arterial recanalization therapy, the blood supply to facial skin was restored and skin wounds recovered in all patients. Only 1 patient was left with small and superficial scars. CONCLUSION: Superselective intra-arterial recanalization therapy is an effective and safe method that can alleviate skin wounds caused by HA vascular embolization. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Superselective Arterial Hyaluronidase Thrombolysis is an Effective Treatment for Hyaluronic Acid-Induced Retinal Artery Occlusion: Study in a Rabbit Model.

BACKGROUND: There are serious complications associated with hyaluronic acid (HA) facial injections, including vision impairment due to retinal artery ischemia. In this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in rabbit. We used this to verify the efficacy of hyaluronidase intra-artery thrombolysis in the treatment of hyaluronic acid-induced retinal artery occlusion. METHODS: Retinal artery ischemia was induced by injecting HA into the ophthalmic artery (OA) of adult chinchilla rabbit, and reperfusion was achieved by intra-artery thrombolysis therapy with hyaluronidase following 60 min and 4 h of occlusion. Digital subtraction angiography (DSA) and fundus fluorescein angiography (FFA) were used to evaluate blood flow in the retina. Electroretinogram (ERG), hematoxylin and eosin staining and transmission electron microscope were used to evaluate the structure and function of the retina after ischemia and reperfusion following 60 min and 4 h of occlusion. RESULTS: DSA and FFA images confirmed occlusion of the ophthalmic and central retinal arteries, as well as reperfusion after hyaluronidase thrombolysis. ERG indicated retinal dysfunction following ischemia, and thrombolysis partially rescued its impairment following 4 h of occlusion. Hematoxylin and eosin staining and TUNEL staining revealed ischemia-induced histological damages in the retina at different time windows, and hyaluronidase thrombolysis partially mitigated these damages. CONCLUSIONS: We report a method to establish a HA-induced retinal artery occlusion animal model. Hyaluronidase intra-artery thrombolysis was used to recanalize the embolized OA at different time points. Using our method, we achieved retinal reperfusion, and an improvement was observed in the visual function of rabbits after hyaluronidase thrombolysis following 4 h of occlusion. We believe that hyaluronidase intra-artery thrombolysis is an effective method to treat HA-induced retinal artery occlusion in clinic. LEVEL OF EVIDENCE II: 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 .

"Filler-Associated Acute Stroke Syndrome": Classification, Predictive Modelling of Hyaluronidase Efficacy, and Updated Case Review on Neurological and Visual Complications.

INTRODUCTION: The rising use of soft tissue fillers for aesthetic procedures has seen an increase in complications, including vascular occlusions and neurological symptoms that resemble stroke. This study synthesizes information on central nervous system (CNS) complications post-filler injections and evaluates the effectiveness of hyaluronidase (HYAL) treatment. METHODS: A thorough search of multiple databases, including PubMed, EMBASE, Scopus, Web of Science, Google Scholar, and Cochrane, focused on publications from January 2014 to January 2024. Criteria for inclusion covered reviews and case reports that documented CNS complications related to soft tissue fillers. Advanced statistical and computational techniques, including logistic regression, machine learning, and Bayesian analysis, were utilized to dissect the factors influencing therapeutic outcomes. RESULTS: The analysis integrated findings from 20 reviews and systematic analyses, with 379 cases reported since 2018. Hyaluronic acid (HA) was the most commonly used filler, particularly in nasal region injections. The average age of patients was 38, with a notable increase in case reports in 2020. Initial presentation data revealed that 60.9% of patients experienced no light perception, while ptosis and ophthalmoplegia were present in 54.3 and 42.7% of cases, respectively. The statistical and machine learning analyses did not establish a significant linkage between the HYAL dosage and patient recovery; however, the injection site emerged as a critical determinant. CONCLUSION: The study concludes that HYAL treatment, while vital for managing complications, varies in effectiveness based on the injection site and the timing of administration. The non-Newtonian characteristics of HA fillers may also affect the incidence of complications. The findings advocate for tailored treatment strategies incorporating individual patient variables, emphasizing prompt and precise intervention to mitigate the adverse effects of soft tissue fillers. LEVEL OF EVIDENCE III: 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 .

Comparison of the effects of submucosal hyaluronidase and dexamethasone on postoperative edema, pain, trismus, and infection following impacted third molar surgery.

BACKGROUND: Limiting postoperative edema, pain, trismus, and infection is crucial for smooth healing. This prospective, controlled clinical trial investigated and compared the effectiveness of dexamethasone and hyaluronidase in relieving these complications. METHODS: In groups Ia and IIa, 8 mg of dexamethasone and 150 IU of hyaluronidase were administered following the removal of impacted teeth, respectively. The contralateral sides (groups Ib and IIb) were determined as control groups. Edema, pain, trismus, and infection were clinically evaluated on the 1st, 2nd, 3rd, and 7th postoperative days. RESULTS: 60 patients were enrolled in the study. Hyaluronidase provided significantly more edema relief than dexamethasone on the 1st, 2nd, 3rd, and 7th postoperative days (P = 0.031, 0.002, 0.000, and 0.009, respectively). No statistical difference was found between dexamethasone and hyaluronidase in VAS and rescue analgesic intake amount values for all time points. Hyaluronidase was more effective in reducing trismus than dexamethasone on the 2nd and 3rd postoperative days (P = 0.029, 0.024, respectively). Neither of the agents significantly increased the postoperative infection rate. CONCLUSIONS: Hyaluronidase can be selected when postoperative excessive edema and trismus are anticipated. Dexamethasone may be a cost-effective option if postoperative pain control is merely targeted. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Protocol Registration and Results System (ClinicalTrials.gov identifier number: NCT05466604) on 20/07/2022.

A clinical study of the local injection of a freshly manufactured 35 kDa hyaluronan fragment for treating chronic wounds.

This study manufactured a 35 kDa hyaluronan fragment (HA35) by enzymatically degrading high-molecular-weight HA using hyaluronidase PH20 derived from bovine testis. The research then examined the therapeutic efficacy of locally administered, tissue-permeable HA35 in alleviating chronic wounds and their associated neuropathic pain. For 20 patients with nonhealing wounds and associated pain lasting over three months, 100 mg of HA35 was injected daily into the healthy skin surrounding the chronic wound for 10 days. Self-assessments before and after treatment indicated that HA35 significantly enhanced wound healing. This was evidenced by the formation of fresh granulation tissue on the wounds (p < 0.0001); reduced darkness, redness, dryness, and damage in the skin surrounding the wounds (p < 0.0001), and a decrease in wound size (p < 0.001). Remarkably, HA35 injections alleviated pain associated with chronic wounds within 24 hours (p < 0.0001). It can be concluded that the low-molecular-weight hyaluronan fragment HA35 potentially enhances the immune response and angiogenesis during wound healing.

[Effectiveness and interest of retrobulbar hyaluronidase injections in the treatment of blindness complicating facial hyaluronic acid injections: A literature review]. / Efficacité et intérêt des injections rétrobulbaires de hyaluronidase dans le traitement des cécités compliquant une injection faciale d'acide hyaluronique : revue de la littérature.

INTRODUCTION: Hyaluronic acid injections are becoming increasingly common among both the general public and the medical community, but they are not without risks. The occurrence of blindness, although rare, is a tragic event for both the patient and the practitioner. One of the treatments proposed in the literature is to inject hyaluronidase as close as possible to the site of ischemia, retrobulbarly. The aim of our study is to evaluate the effectiveness and potential benefits of retrobulbar hyaluronidase injections. MATERIALS AND METHODS: A literature review was conducted using the PubMed database. Only articles addressing retrobulbar hyaluronidase injections for the treatment of blindness following hyaluronic acid injections were included. RESULTS: We identified 12 case reports or series, comprising a total of 16 patients. Among these 16 patients, 3 regained their vision. Hyaluronidase was injected between 20minutes and 7days after the onset of the complication, with injected doses ranging from 3×150IU to 3×1500IU. DISCUSSION: Literature reveals only 3 cases of successful treatment out of the 16 reported injections. The time interval before retrobulbar injection, as well as the dose and the experience of the injecting practitioner, may influence the success rate of this treatment. Other treatments, such as intravascular hyaluronidase injections, remain to be explored.

A Phase 1 Open-Label Study to Assess the Tolerability, Safety, and Immunogenicity of Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 20% in Healthy Adults.

PURPOSE: Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 20% will allow reduced infusion volumes and frequency versus existing subcutaneous therapies such as fSCIG 10% and conventional subcutaneous immunoglobulin 20%, respectively. We assessed the tolerability, safety, and immunogenicity of warmed and unwarmed fSCIG 20%. METHODS: This phase 1, single-dose, open-label, three-arm study enrolled healthy adults aged 19-50 years (inclusive) at a single US center (NCT05059977). Post-screening, participants received a single fSCIG 20% dose comprising recombinant human hyaluronidase and varying doses of in-line warmed or unwarmed immunoglobulin G (IgG) during a 4-day treatment period in a sentinel and sequential dosing design (treatment arm 1, warmed IgG 20% 0.4 g/kg; treatment arm 2, warmed IgG 20% 1.0 g/kg; treatment arm 3, unwarmed IgG 20% 1.0 g/kg). Participants were followed for 12 (± 1) weeks post-infusion. The primary endpoint was tolerability ("tolerable" infusions were not interrupted, stopped, or reduced in rate owing to fSCIG 20%-related treatment-emergent adverse events (TEAEs)). Secondary endpoints included occurrence of TEAEs. RESULTS: Overall, 24 participants were included, 8 per treatment arm (mean age 39.0 years, 54.2% men). All participants tolerated the infusions. All TEAEs were mild (107 events, in all participants), and all participants experienced fSCIG 20%-related (105 events) and local (102 events) TEAEs. Infusion site erythema and infusion site swelling were most frequently reported. No serious TEAEs occurred, and no participants discontinued the study owing to TEAEs. CONCLUSION: fSCIG 20% was well-tolerated with a favorable safety profile in healthy adults. Future studies will evaluate fSCIG 20% in primary immunodeficiency diseases. Trial registration number (ClinicalTrials.gov): NCT05059977 (registered 28 September 2021).

Dual Stromal Targeting Sensitizes Pancreatic Adenocarcinoma for Anti-Programmed Cell Death Protein 1 Therapy.

BACKGROUND & AIMS: The stroma in pancreatic ductal adenocarcinoma (PDAC) contributes to its immunosuppressive nature and therapeutic resistance. Herein we sought to modify signaling and enhance immunotherapy efficacy by targeting multiple stromal components through both intracellular and extracellular mechanisms. METHODS: A murine liver metastasis syngeneic model of PDAC was treated with focal adhesion kinase inhibitor (FAKi), anti-programmed cell death protein 1 (PD-1) antibody, and stromal hyaluronan (HA) degradation by PEGylated recombinant human hyaluronidase (PEGPH20) to assess immune and stromal modulating effects of these agents and their combinations. RESULTS: The results showed that HA degradation by PEGPH20 and reduction in phosphorylated FAK expression by FAKi leads to improved survival in PDAC-bearing mice treated with anti-PD-1 antibody. HA degradation in combination with FAKi and anti-PD-1 antibody increases T-cell infiltration and alters T-cell phenotype toward effector memory T cells. FAKi alters the expression of T-cell modulating cytokines and leads to changes in T-cell metabolism and increases in effector T-cell signatures. HA degradation in combination with anti-PD-1 antibody and FAKi treatments reduces granulocytes, including granulocytic- myeloid-derived suppressor cells and decreases C-X-C chemokine receptor type 4 (CXCR4)-expressing myeloid cells, particularly the CXCR4-expressing granulocytes. Anti-CXCR4 antibody combined with FAKi and anti-PD-1 antibody significantly decreases metastatic rates in the PDAC liver metastasis model. CONCLUSIONS: This represents the first preclinical study to identify synergistic effects of targeting both intracellular and extracellular components within the PDAC stroma and supports testing anti-CXCR4 antibody in combination with FAKi as a PDAC treatment strategy.

Early ultrasound for diagnosis and treatment of vascular adverse events with hyaluronic acid fillers.

BACKGROUND: Hyaluronic acid fillers are known for a reliable safety profile, but complications do occur, even serious vascular adverse events. OBJECTIVE: To improve the treatment outcome after a vascular adverse event with use of hyaluronic acid filler treatments. METHODS: Duplex ultrasonography is used to detect the hyaluronic acid filler causing the intra-arterial obstruction. RESULTS: If treated in time, 1 single treatment of ultrasonographically guided injections of hyaluronidase into the filler deposit will prevent skin necrosis. CONCLUSION: Because the use of duplex ultrasonography adds extra essential information, its use may become an integral part of the prevention and treatment of injection adverse events.

Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial.

BACKGROUND AND AIMS: ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse. METHODS: ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial conducted at 54 sites in 21 countries. Eligible adults had definite or probable CIDP and adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores of 0-7 (inclusive), and received stable intravenous immunoglobulin (IVIG) for ≥12 weeks before screening. After stopping IVIG, patients were randomized 1:1 to fSCIG 10% or placebo for 6 months or until relapse/discontinuation. fSCIG 10% was administered at the same dose (or matching placebo volume) and interval as pre-randomization IVIG. The primary outcome was patient proportion experiencing CIDP relapse (≥1-point increase in adjusted INCAT score from pre-subcutaneous treatment baseline) in the modified intention-to-treat population. Secondary outcomes included time to relapse and safety endpoints. RESULTS: Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (n = 62) or placebo (n = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (n = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs n = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: -21.8% [-34.5%, -7.9%], p = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (p = .002). Adverse events (AEs) were more frequent with fSCIG 10% (79.0% of patients) than placebo (57.1%), but severe (1.6% vs 8.6%) and serious AEs (3.2% vs 7.1%) were less common. INTERPRETATION: fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.

Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathy.

BACKGROUND: Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD), is a global leading cause of vision loss in older populations. Distinct from typical AMD, PCV is characterized by polyp-like dilatation of blood vessels and turbulent blood flow in the choroid of the eye. Gold standard anti-vascular endothelial growth factor (anti-VEGF) therapy often fails to regress polypoidal lesions in patients. Current animal models have also been hampered by their inability to recapitulate such vascular lesions. These underscore the need to identify VEGF-independent pathways in PCV pathogenesis. RESULTS: We cultivated blood outgrowth endothelial cells (BOECs) from PCV patients and normal controls to serve as our experimental disease models. When BOECs were exposed to heterogeneous flow, single-cell transcriptomic analysis revealed that PCV BOECs preferentially adopted migratory-angiogenic cell state, while normal BOECs undertook proinflammatory cell state. PCV BOECs also had a repressed protective response to flow stress by demonstrating lower mitochondrial functions. We uncovered that elevated hyaluronidase-1 in PCV BOECs led to increased degradation of hyaluronan, a major component of glycocalyx that interfaces between flow stress and vascular endothelium. Notably, knockdown of hyaluronidase-1 in PCV BOEC improved mechanosensitivity, as demonstrated by a significant 1.5-fold upregulation of Krüppel-like factor 2 (KLF2) expression, a flow-responsive transcription factor. Activation of KLF2 might in turn modulate PCV BOEC migration. Barrier permeability due to glycocalyx impairment in PCV BOECs was also reversed by hyaluronidase-1 knockdown. Correspondingly, hyaluronidase-1 was detected in PCV patient vitreous humor and plasma samples. CONCLUSIONS: Hyaluronidase-1 inhibition could be a potential therapeutic modality in preserving glycocalyx integrity and endothelial stability in ocular diseases with vascular origin.

The Utility of Hyaluronidase for the Free and Pedicle Flap Salvage.

Hyaluronidase is commonly used to treat swelling and hematoma for aesthetic and reconstructive purposes. It has also been reported as a stimulator of angiogenesis. The purpose of this study was to introduce the utility of hyaluronidase in patients with flap compromise after free and pedicle flap reconstructions. This study was a retrospective study of 1 case of radial forearm free flap salvage, 2 cases of keystone perforator flap salvage, and 1 case of pectoralis major myocutaneous flap salvage. A radial forearm free flap reconstruction of unilateral mouth floor and tongue defect was complicated with hematoma formation on a postoperative day 1 after taking clopidogrel due to acute-onset non-ST-elevation myocardial infarction but dramatically resolved with hyaluronidase injection into the flap and contralateral unaffected tongue. After this intervention, the flap color dramatically returned to normal and became soft without further treatments. Two keystone design perforator flaps were performed to reconstruct the sacral defect after the debridement of pressure ulcers. Two cases were related to the patients' medical conditions, such as low platelet count caused by liver cirrhosis. We also salvaged pectoralis major myocutaneous flap in a 91-year-old female patient with large breasts. This study introduced our experience of salvaging the free and pedicled flaps using hyaluronidase. Hyaluronidase is an excellent option when arterial or venous insufficiency occurs after free and perforator flap surgeries.

[Vascular occlusion following profile harmonization of the chin with hyaluronic acid fillers]. / Vasculaire occlusie na profielharmonisatie van de kin met hyaluronzuur fillers.

The use of dermal fillers for cosmetic procedures has increased rapidly both worldwide and in the Netherlands in recent years, which has led to an absolute increase in reported side effects and complications. Although most of these complications are mild, serious complications such as vascular occlusion can also occur. In this article, we describe a case of a 35-year-old woman who showed signs of reduced tissue perfusion and the early stage of skin necrosis following injection of hyaluronic acid fillers in the chin. This complication was successfully treated by ultrasound-guided injection of hyaluronidase, resulting in a full recovery without residual symptoms. To minimize the risk of serious complications treatment with hyaluronic acid fillers should be carried out by an experienced practitioner.

Virulence, phenotype and genotype characteristics of invasive group B Streptococcus isolates obtained from Swedish pregnant women and neonates.

Group B streptococci (GBS) are bacteria that can cause preterm birth and invasive neonatal disease. Heterogeneous expression of virulence factors enables GBS to exist as both commensal bacteria and to become highly invasive. A molecular epidemiological study comparing GBS bacterial traits, genotype and host characteristics may indicate whether it is possible to predict the risk of perinatal invasive GBS disease and more accurately target intrapartum antibiotic prophylaxis. A total of 229 invasive GBS isolates from Swedish pregnant women or neonates were assessed for virulence and phenotypic traits: hemolysis zone, hemolytic pigment (Granada agar), Streptococcus B Carrot Broth (SBCB) assay, CAMP factor, and hyaluronidase activity. Genes regulating hemolytic pigment synthesis (covR/covS, abx1, stk1, stp1) were sequenced. Of the virulence factors and phenotypes assessed, a Granada pigment or SBCB score ≥ 2 captured more than 90% of EOD isolates with excellent inter-rater reliability. High enzyme activity of hyaluronidase was observed in 16% (36/229) of the invasive GBS isolates and notably, in one case of stillbirth. Hyaluronidase activity was also significantly higher in GBS isolates obtained from pregnant/postpartum individuals versus the stillbirth or neonatal invasive isolates (p < 0.001). Sequencing analysis found that abx1 (g.T106I), stk1 (g.T211N), stp1 (g.K469R) and covS (g.V343M) variants were present significantly more often in the higher (Granada pigment score ≥ 2) versus lower pigmented isolates (p < 0.001, each variant). Among the 203 higher Granada pigment scoring isolates, 22 (10.8%) isolates had 3 of the four sequence variants and 10 (4.9%) had 2 of the four sequence variants. Although heterogeneity in GBS virulence factor expression was observed, the vast majority were more highly pigmented and contained several common sequence variants in genes regulating pigment synthesis. High activity of hyaluronidase may increase risk for stillbirth and invasive disease in pregnant or postpartum individuals. Our findings suggest that testing for GBS pigmentation and hyaluronidase may, albeit imperfectly, identify pregnant people at risk for invasive disease and represent a step towards a personalized medical approach for the administration of intrapartum antibiotic prophylaxis.

Cutaneous Vascular Compromise and Resolution of Skin Barrier Breakdown After Dermal Filler Occlusion-Implementation of Evidence-Based Recommendations Into Real-World Clinical Practice.

BACKGROUND: Vascular occlusions that threaten skin integrity, although not an emergency like those that threaten a patient's vision, is an urgent situation. Accurately interpreting physical examination findings is paramount. The use of high-dose, pulsed hyaluronidase is the mainstay of therapy; however, adjunctive measures that may optimize clearance of an occlusion and/or skin barrier repair such as the use of image guidance and hyperbaric oxygen should be considered. OBJECTIVE: To provide a review of the literature on the treatment of vascular occlusions threatening skin barrier integrity and develop a step-wise treatment guide. MATERIALS AND METHODS: The authors searched PubMed for peer-reviewed studies, consensus statements, case series, and case reports using a variety of keywords. RESULTS: Twenty-six articles focusing on vascular occlusions threatening the skin barrier were reviewed. The authors collectively agreed on treatments to reverse vascular occlusions and restore the skin barrier. The importance of high-dose, pulsed hyaluronidase was clear. Therapies that lacked evidence such as sodium thiosulfate were also revealed. CONCLUSION: A vascular occlusion that threatens skin integrity is an urgent matter which requires accurate interpretation of physical examination findings that will help guide intervention. High-dose, pulsed hyaluronidase along with adjunctive measures performed in a step-wise manner is key to an optimal outcome.

Muscle Activity in Pre-Treatment and Post-Treatment Oral Submucous Fibrosis Patients: Electromyography Study.

Background: Oral submucous fibrosis (OSMF) is a premalignant condition of insidious onset which affects the oral mucosa, pharynx, and esophagus. The muscles of mastication are known to be affected resulting in limited mouth opening. Electromyography (EMG) is a sophisticated method of measuring and evaluating muscle activity. Previously, EMG was primarily utilized in medical sciences, but it is currently being used extensively in both the medical and dentistry fields. Objectives: The aim of the study is to evaluate the electromyographic activity of masseter muscle in OSMF patients before and after treatment and to compare with healthy controls. Materials and Methods: This prospective case-control clinical study comprised 180 OSMF patients who were divided into four groups and 45 healthy individuals served as the control group. The OSMF individuals were injected with hyaluronidase 1,500 IU mixed in 1.5 ml of dexamethasone and 0.5 ml of lignocaine HCL intralesionally twice a week for one month along with a basic physiotherapy regimen consisting of mouth exercises two times daily. The control subjects were given placebo capsules. The treatment was carried out for a month and the electromyographic masseter muscle activity was evaluated among the OSMF patients and control group before and after treatment. Results: The results revealed that the electromyographic activity of master muscles in OSMF patients showed increased activity when compared with healthy controls. Patients with OSMF showed decreased muscle activity after treatment. Conclusion: When compared with healthy controls, OSMF patients had higher electromyographic activity of the masseter muscles and the muscle activity was decreased following treatment. In OSMF patients, EMG may help in determining the involvement of the mastication and facial expression muscles. It can also be used as a diagnostic tool to assess the treatment outcome of muscle activity in OSMF patients.

Treatment of a neonatal peripheral intravenous infiltration/extravasation (PIVIE) injury with hyaluronidase: a case report.

INTRODUCTION: Intravenous therapy-related injury, its prevention, and treatment are ubiquitous topics of interest among neonatal clinicians and practitioners. This is due to the economic costs, reputational censure, and patents' wellbeing concerns coupled with the possibility of potentially avoidable serious and life-long harm occurring in this vulnerable patient population. CASE DESCRIPTION: A term infant receiving a hypertonic dextrose infusion for the management of hypoglycemia developed a fulminating extravasation shortly after commencement of the infusion. This complication developed without notification of infusion pump pressure changes pertaining to a change in blood vessel compliance or early warning of infiltration by the optical sensor site monitoring technology (ivWatch®) in use. The injury was extensive and treated with a hyaluronidase/saline mix subcutaneously injected into the extravasation site using established techniques. Over a period of 2 weeks, the initially deep wound healed successfully without further incident, and the infant was discharged home without evident cosmetic scarring or functional effects. CONCLUSION: This article reports on a case of a term baby who postroutine insertion of a peripherally intravenous catheter showed an extreme reaction to extravasation of the administered intravenous fluids. We discuss the condition, our successful management with hyaluronidase, and the need to remain observationally vigilant of intravenous infusions despite the advances in infusion monitoring technology. HIGHLIGHTS: In a neonatal population peripheral infusion therapy-related complication rates have been reported to be as high as 75% Peripheral IV infiltration and extravasation (PIVIE) is implicated in up to 65% of IV-related complications PIVIE injury has the potential to cause serious harm Prompt recognition and timely appropriate intervention can mitigate many of these risks Adhering to the 5Rs for vascular access optimizes infusion therapy and potentially reduces complications.

COVID-19 and Dermal Fillers: Should We Really Be Concerned? / COVID y rellenos faciales ¿realmente debemos preocuparnos?

SARS-CoV-2 has caused millions of infections and deaths worldwide and case numbers continue to rise. Besides the effect of the virus on key organs - leading to respiratory illness, anosmia, diarrhea, and fever and other complications - delayed inflammatory reactions to hyaluronic acid dermal fillers, mainly in the face, have also been reported to occur after confirmed SARS-CoV-2 infections and in vaccinated individuals. While delayed inflammatory reactions tend to be self-limiting, they should be diagnosed and treated with corticosteroids, hyaluronidase, and/or antibiotics when necessary. The inflammation is generally not severe, yet these complications are classified as serious adverse events by the US Food and Drug Administration. They appear to be delayed type IV hypersensitivity reactions triggered by the immune system in the presence of SARS-CoV-2 or other viruses, such as those causing influenza, although the underlying mechanisms have not been fully elucidated. Because the longevity of dermal fillers is increasing, while the pandemic continues to evolve and new vaccines are under development, the long-term effects on hyaluronic acid fillers and other bioimplant materials should be studied. Physicians must also be encouraged to report these reactions, however mild, to ensure accurate records.