Adequate Wound Healing Research Articles

Prosthetic joint infection caused by Mediterraneibacter gnavus following total knee arthroplasty, challenges in anaerobic bacteria identification

BackgroundMediterraneibacter gnavus is a Gram positive, non-sporulated, obligate anaerobe diplococci. It was first described in 1974 by Moore et al. (under the name Ruminococcus gnavus) from faeces and contents of the gastrointestinal tract of humans. It is a relatively common member of the human gut microbiota, nevertheless its role as a pathogenic bacterium has not been completely elucidated yet and it seems to depend on numerous factors, including those of the host. Here we present a case of prosthetic joint infection following total knee arthroplasty by M. gnavus.Case presentationA 74 years old patient was admitted to the emergency department presenting with acute onset of left knee pain and swelling 20 days after total left knee arthroplasty. Follow-up revealed erythema and oedema without signs of fluctuation or purulent discharge from the surgical wound and elevated inflammatory reactants. Synovial fluid was taken for bacterial culture and antibiotic treatment with ceftazidime and daptomycin was established. Examination of the synovial fluid revealed abundant polymorphonuclear leucocytes, without visualizing bacteria. After four days of incubation, anaerobic culture exhibit growth of small, grey, umbilicated colonies in pure culture on Schaedler agar. The microorganism was identified as R. gnavus by MALDI-TOF (Bruker Daltonics) and M. gnavus by 16S ribosomal bacterial sequencing. The isolated showed susceptibility to the most commonly used anaerobicidal antibiotics except for clindamycin. Surgical treatment and infection source control included DAIR (debridement, antibiotics, and implant retention) and vacuum assisted therapy. The patient was discharged after six weeks with a 3-month course of oral amoxicillin as consolidation therapy. Subsequent follow-up revealed adequate wound healing with no signs of infection.ConclusionsMediterraneibacter gnavus have been reported as the causal microorganism in a range of human infections, nevertheless its identification remains challenging. Infection of prosthetic joints by anaerobic microorganisms is uncommon and is not considered in its empirical antibiotic treatment, thus, correct and swift identification of anaerobic bacteria in these cases is paramount.

Enhancing Infected Diabetic Wound Healing through Multifunctional Nanocomposite-Loaded Microneedle Patch: Inducing Multiple Regenerative Sites.

Infected diabetic wound (DW) presents a prolonged and challenging healing process within the field of regenerative medicine. The effectiveness of conventional drug therapies is hindered by their limited ability to reach deep tissues and promote adequate wound healing rates. Therefore, there is an imperative to develop drug delivery systems that can penetrate deep tissues while exhibiting multifunctional properties to expedite wound healing. In this study, w e devised a soluble microneedle (MN) patch made of γ-PGA, featuring multiple arrays, which w as loaded with core-shell structured nanoparticles (NPs) known as Ag@MSN@CeO2, to enhance the healing of infected DWs. The NP comprises a cerium dioxide (CeO2) core with anti-inflammatory and antioxidant properties, a mesoporous silica NP (MSN) shell with angiogenic characteristics, and an outermost layer doped with Ag to combat bacterial infections. W e demonstrated that the MN platform loaded with Ag@MSN@CeO2 successfully penetrated deep tissues for effective drug delivery. These MN tips induced the formation of multiple regenerative sites at various points, leading to antibacterial, reactive oxygen species-lowering, macrophage ecological niche-regulating, vascular regeneration-promoting, and collagen deposition-promoting effects, thus significantly expediting the healing process of infected DWs. Considering these findings, the multifunctional MN@Ag@MSN@CeO2 patch exhibits substantial potential for clinical applications in the treatment of infected DW.

Time to therapy and safety of testicular tissue cryopreservation in children undergoing gonadotoxic treatment or hematopoietic stem cell transplant

BackgroundWith the use of multimodal treatments and hematopoietic stem cell transplant, the majority of children diagnosed with malignancies and hematologic diseases are now surviving into adulthood. Due to the gonadotoxic effects and potential for future infertility associated with many of these treatments, fertility counseling with sperm cryopreservation prior to starting therapy is the standard of care for post-pubertal males. Unfortunately, the options are limited for pre-pubertal patients or those unable to provide a specimen. Testicular tissue cryopreservation (TTC) is an investigational method to surgically obtain germ cells from testicular tissue and potentially restore future spermatogenesis. While TTC has been shown to be safe, little is reported on the time to treatment following the procedure to ensure adequate wound healing and avoid delays in definitive therapy. ObjectivesThe primary outcome was the time to initiation of treatment following TTC. Secondary outcomes were complication rates, delays in treatment due to TTC, and presence of germ cells. MethodsWe conducted a single-institution retrospective cohort study of patients undergoing TTC between 2017-2023. Patients at significant risk for treatment related infertility based on established criteria were eligible for TTC. Patients were excluded if they received their oncology or hematology care elsewhere. All patients were enrolled in an IRB approved research protocol with 75% of the tissue submitted for cryopreservation and 25% for research purposes. Time to therapy was defined as the first receipt of gonadotoxic treatment following TTC. ResultsA total of 122 patients (53=malignant, 69=non-malignant) underwent TTC with a median age of 5.9 years (IQR 2.3-9.35). Germ cells were identified in 115 (94%) specimens. A total of 109 (89%) patients underwent concomitant procedures. The median time to initiation of therapy was 5 (IQR 1.0-7.0) and 7 days (IQR 6.0-13.0) for malignant and non-malignant disease, respectively. The 30-day surgical complication rate was 2.5% and was similar between malignant vs non-malignant diagnoses (p=0.58). All surgical complications were managed non-operatively. No patients had a delay in definitive treatment due to concern for wound healing or complications. DiscussionOur surgical complication rates are similar to previous studies and are not affected by the time to treatment following TTC. Limitations of the study are its retrospective design, single institution, and short-term follow up. ConclusionTTC can be performed safely, efficiently, and in conjunction with other necessary procedures without resulting in delays of definitive treatment . TTC affords the opportunity for fertility preservation in children who have no other options.

Chitosan/starch based unoxidized tannic acid modified microparticles for rapid hemostasis with broad spectrum antibacterial activity

The development of a rapid hemostat through a facile method with co-existing antibacterial activity and minimum erythrocyte lysis property stands as a major requirement in the field of hemostasis. Herein, a series of novel microparticle hemostats were synthesized using chitosan, different hydrothermally-treated starches, and cross-linked with tannic acid (TA) simultaneously in an unoxidized environment via ionotropic gelation method. Hemostats' comparative functional properties, such as adjustable antibacterial and erythrocyte compatibility upon various starch additions were evaluated. The in vivo hemostatic study revealed that the developed hemostats for mouse liver laceration and rat tail amputation had clotting times (13 s and 38 s, respectively) and blood loss (51 mg and 62 mg, respectively) similar to those of Celox™. The erythrocyte adhesion test suggested that erythrocyte distortion can be lowered by modifying the antibacterial hemostats with different starches. The broad-spectrum antibacterial efficacy of the hemostats remained intact against S. aureus (>90 %), E. coli (>80 %), and P. mirabilis bacteria upon starch modification. They also demonstrated high hemocompatibility (<3 % hemolysis ratio), moderate cell viability (>81 %), in vivo biodegradation, and angiogenesis indicating adequate biocompatibility and wound healing. The developed hemostats hold significant promise to be employed as rapid hemostatic agents for preventing major bleeding and bacterial infection in emergencies.

Automated Prediction of Photographic Wound Assessment Tool in Chronic Wound Images

Many automated approaches have been proposed in literature to quantify clinically relevant wound features based on image processing analysis, aiming at removing human subjectivity and accelerate clinical practice. In this work we present a fully automated image processing pipeline leveraging deep learning and a large wound segmentation dataset to perform wound detection and following prediction of the Photographic Wound Assessment Tool (PWAT), automatizing the clinical judgement of the adequate wound healing. Starting from images acquired by smartphone cameras, a series of textural and morphological features are extracted from the wound areas, aiming to mimic the typical clinical considerations for wound assessment. The resulting extracted features can be easily interpreted by the clinician and allow a quantitative estimation of the PWAT scores. The features extracted from the region-of-interests detected by our pre-trained neural network model correctly predict the PWAT scale values with a Spearman's correlation coefficient of 0.85 on a set of unseen images. The obtained results agree with the current state-of-the-art and provide a benchmark for future artificial intelligence applications in this research field.

Management and maintenance of oral health: Personalized primary prevention strategies and protocols in patients at risk of developing medication-related osteonecrosis of the jaw

Skeletal complications arising from osteoporosis or bone metastases are associated with considerable pain, increased mortality, and diminished quality of life. Agents that prevent bone resorption, such as bisphosphonates, denosumab, and antiangiogenic agents, prove effective in reducing fracture risk and find extensive use in patients with osteoporosis or bone cancer metastases. Medication-related osteonecrosis of the jaw (MRONJ) is a potentially serious adverse event associated with high cumulative doses of antiresorptive drugs. Other risk factors for osteonecrosis of the jaw include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, inappropriate dentures, and other MRONJ-related medications. Preventive strategies encompass completing necessary oral surgery before initiating antiresorptive drug therapy, administering antibiotics before and/or after the procedure, rinsing the mouth with chlorhexidine, ensuring adequate wound healing post-tooth extraction, and maintaining good oral hygiene. The primary goal of treatment is to improve the patient&amp;rsquo;s quality of life by managing pain and infection, preventing the development of new lesions, and decelerating disease progression. Dentists and dental hygienists, operating within a multi-professional team, play a key role in the primary prevention of MRONJ. However, a standardized multidisciplinary approach, fostering sustained dialog between specialists involved in the management of patients at risk for MRONJ, remains essential. This review describes the preventive and individualized oral hygiene management in patients at risk for this condition.

AN AYURVEDIC APPROACH IN THE MANAGEMENT OF OSTEOMYELITIS TOES

Background – Osteomyelitis toe is commonly seen in patients who have peripheral neuropathy associated with diabetic mellitus. In Ayurveda, osteomyelitis can be correlated with Asthimajja Vidradhi1 or Dusta Vrana. Dusta vrana (infected wound) can cause loss of physical activity and it can produce a significant impact on the quality of life. This study mainly concentrates on Vrana Shodhan karma (surgical debridement) of dusta vrana (infected wound) and followed by application of Karanjadi Ghrita with Shaman Chikitsa which is performed to restore the function of toe and achieve adequate wound healing. Material and method- A Fifty-eight-year-old male pa-tient came to Shalya tantra OPD of our institute (GAC Raipur) with complaints of non-healing wounds on his great and second toe of left foot along with pain, swelling and discoloration of skin. Routine blood investigation and foot x-ray was taken and was diagnosed as osteomyelitis toe. Under all aseptic manner surgical debridement of necrotic tissue(slough) of wound was done by following classical guideline of Sushruta Samhita. Simultane-ously, wounds cleaned by lukewarm water and alcohol then after wounds was dressed in use of Karanjadi Ghri-ta and following internal medicine were given to the patient for three months like Triphala Guggulu, Kaishora Guggulu, Lakshadi Guggulu, Varunadi Kashayam. Result- Significant output were observed like pain, oedema is subsided, and wound was completely healed within 3 months. Conclusion- Multidisciplinary Ayurvedic ap-proach can play a good supportive role in managing critical conditions such as diabetic osteomyelitis toe and cosmetically preserve the body part and amputation can be avoided.

Development of a hybrid hydrogel for submucosal injection in endoscopic resection of gastrointestinal neoplasm: From laboratory to clinical trial.

Background and study aims Submucosal injection solution is essential for successful endoscopic resection of the early gastrointestinal tumor. We evaluated a new endoscopic hydrogel for submucosal injection and its clinical feasibility. Patients and methods A hydrogel (AceGel) containing 0.4% sodium alginate and 2% calcium lactate was developed for ex vivo and animal studies. Subsequently, a prospective, single-arm study was conducted to assess its feasibility and safety in humans. Patients with gastrointestinal neoplasms undergoing endoscopic resection were enrolled. All patients underwent endoscopic surveillance after 4 weeks and outpatient follow-up at week 6. Afterward, they received endoscopic follow-up according to the medical routine. Results In the ex vivo experiments, the submucosal elevation height of AceGel was equivalent to sodium hyaluronate and superior to saline or glycerol. Animal studies showed that the excised wounds healed well without surrounding tissue damage. Twelve patients participated in the clinical trial, including three, two, and seven patients with esophageal, gastric, and colonic lesions, respectively. The mean neoplasm size and submucosal injection volumes were 24.0±8.6 mm and 22.8±19.9 mL, respectively. All patients had adequate wound healing on 4-week surveillance endoscopy, and none had serious adverse events during 6-week follow-up. Moreover, endoscopic follow-up showed complete wound healing after 6 to 46 months without local mucosal inflammation in all patients. Conclusions AceGel is good for endoscopic submucosal injection and demonstrated its usefulness in durable mucosal elevation for endoscopic therapy in preclinical tests. This clinical trial shows its safety and feasibility in all participating patients.

219 Post-Skin Cancer Scalp Defect Reconstruction with Integra® as Single Stage Surgery: A Case Series

Abstract Aim Large post-surgical scalp defects represent a common challenge in skin cancer surgery reconstruction. Despite the multiple options available the patients, often elderly, may prefer to have the least amount of surgery done and/or have comorbidities that may impair adequate wound healing. In order to reduce the number of hospital appointments and the risks of COVID19 exposure for the frail patients we used Integra®, a very versatile Dermal Regeneration Template for the treatment of skin defects. Originally, Integra® was designed to be followed by a second-stage surgery with a full thickness skin graft (FTSG). We retrospectively collected, in our busy OMFS Unit, a 40-case series of post-skin cancer scalp defects reconstructed using Integra® as single-stage approach without any further surgery. Method We have carried out a literature review of its use on the scalp and examined a series of parameters from our experience including:defect sizedressing appointments and total healing timeanticoagulation, peri-operative antibiotics prescribingcomplications Results The total healing time for the scalp wounds treated with Integra® averages 3.8 months, requiring 7.8 hospital appointments for dressings and checkups. Two infections, 3 significant bleeds and 4 failures were reported. Conclusions The Integra® is a valid and optimal substitute for local flaps and FTSG in patients that may prefer a single-staged approach wishing to avoid a second surgical site and minimising hospital attendance. The drawbacks are the longer time to heal compared to flaps/FTSG, the costs and the risk of delaying radiotherapy if complete epithelialisation is not achieved.

The extent of unnecessary tooth loss due to extractions prior to radiotherapy based on radiation field and dose in patients with head and neck cancer

Background and purposePrior to radiotherapy (RT), teeth with poor prognosis that pose a risk for post-RT osteoradionecrosis (ORN) are removed. To allow enough time for adequate wound healing prior to RT, decisions are made based on the estimated radiation dose. This study aimed to gain insight into (1) the overall number of teeth extracted and (2) the patient and tumor characteristics associated with the number of redundantly extracted teeth. Materials and methodsPatients with head and neck cancer (HNC), treated with RT between 2015 and 2019, were included in this cross-sectional study. For each extracted tooth the radiation dose was calculated retrospectively. The cut-off point for valid extraction was set at ≥ 40 Gy in accordance with the national protocol. Potential factors for doses ≥ 40 Gy were identified, including age, sex, tumor location, tumor (T) and nodal stage (N), overall tumor stage and number of teeth extracted. ResultsA total of 1759 teeth were removed from 358 patients. Of these 1759 teeth, 1274 (74%) appeared to have been removed redundantly, based on the mean dose (Dmean) of < 40 Gy. Using the maximum dose (Dmax) of < 40 Gy, 1080 teeth (61%) appeared to have been removed redundantly. Tumor location and N-classification emerged as the most important associative variables in the multivariable regression analysis. ConclusionTo our knowledge this is the first study to provide insight into the amount of teeth redundantly extracted prior to RT and represents a step forward in de-escalating the damage to the masticatory system prior to RT.

Innovative Functional Biomaterials as Therapeutic Wound Dressings for Chronic Diabetic Foot Ulcers.

The imbalance of local and systemic factors in individuals with diabetes mellitus (DM) delays, or even interrupts, the highly complex and dynamic process of wound healing, leading to diabetic foot ulceration (DFU) in 15 to 25% of cases. DFU is the leading cause of non-traumatic amputations worldwide, posing a huge threat to the well-being of individuals with DM and the healthcare system. Moreover, despite all the latest efforts, the efficient management of DFUs still remains a clinical challenge, with limited success rates in treating severe infections. Biomaterial-based wound dressings have emerged as a therapeutic strategy with rising potential to handle the tricky macro and micro wound environments of individuals with DM. Indeed, biomaterials have long been related to unique versatility, biocompatibility, biodegradability, hydrophilicity, and wound healing properties, features that make them ideal candidates for therapeutic applications. Furthermore, biomaterials may be used as a local depot of biomolecules with anti-inflammatory, pro-angiogenic, and antimicrobial properties, further promoting adequate wound healing. Accordingly, this review aims to unravel the multiple functional properties of biomaterials as promising wound dressings for chronic wound healing, and to examine how these are currently being evaluated in research and clinical settings as cutting-edge wound dressings for DFU management.

Postoperative drainage management and wound complications following resection of lower limb soft tissue tumors: a retrospective cohort study

PurposePostoperative wound complications are common in patients undergoing resection of lower extremity soft tissue tumors. Postoperative drainage therapy ensures adequate wound healing but may delay or complicate it. The aim of this study is to evaluate the incidence of postoperative wound complications and delayed or prolonged drainage treatment and to propose a standardized definition and severity grading of complex postoperative courses.MethodsA monocentric retrospective analysis of 80 patients who had undergone primary resection of lower extremity soft tissue tumors was performed. A new classification was developed, which takes into account postoperative drainage characteristics and wound complications. Based on this classification, risk factors and the prognostic value of daily drainage volumes were evaluated.ResultsAccording to this new definition, regular postoperative course grade 0 (no wound complication and timely drainage removal) occurred in 26 patients (32.5%), grade A (minor wound complications or delayed drainage removal) in 12 (15.0%), grade B (major wound complication or prolonged drainage therapy) in 31 (38.8%), and grade C (reoperation) in 11 (13.7%) patients. Tumor-specific characteristics, such as tumor size (p = 0.0004), proximal tumor location (p = 0.0484), and tumor depth (p = 0.0138) were identified as risk factors for complex postoperative courses (grades B and C). Drainage volume on postoperative day 4 was a suitable predictor for complex courses (cutoff of 70 ml/d).ConclusionThe proposed definition incorporates wound complications and drainage management while also being clinically relevant and easy to apply. It may serve as a standardized endpoint for assessing the postoperative course after resection of lower extremity soft tissue tumors.

PC17. Implementation of an Enhanced Recovery after Surgery Protocol for Cleft Palate Repair

PURPOSE: Enhanced recovery after surgery (ERAS) protocols have been implemented across surgical disciplines, including cleft surgery, to decrease hospital stays and improve outcomes. The authors aim to describe the implementation of an ERAS protocol for cleft palate repair at a tertiary care hospital. METHOD: Patients undergoing cleft palate repair at the authors’ institution over a 10-year period were collected (n=242). Cleft demographics and operative details were collected. Primary outcome measures were hospital length of stay (LOS) and narcotic usage. Secondary outcome measures were fistula development and need for speech surgery. Chi-square tests and independent t-tests determined significance. RESULTS: Infiltration with bupivacaine was associated with decreased initial 24-hour morphine equivalent usage (p < 0.01) and decreased hospital LOS (p < 0.01). Utilization of the Furlow palatoplasty was associated with decreased hospital LOS (p < 0.01). Patients using the ERAS protocol experienced shorter LOS (p < 0.01). Fistula development was associated with increased 24-hour morphine equivalent usage (p < 0.01). Need for speech surgery was associated with increased 24-hour morphine equivalent usage (p < 0.01) and increased hospital LOS (p < 0.05). CONCLUSION: This study reiterates the benefit of an ERAS protocol for patients undergoing cleft palate repair. The protocol resulted in decreased LOS and narcotic use. The finding regarding fistula formation and need for speech surgery requiring increased narcotics may indicate that the initial postoperative period is vital to adequate wound healing and subsequent outcomes. This study has implications for ways to maximize hospital reimbursement, as well as potentially improve outcomes.

Development of Verapamil Hydrochloride-loaded Biopolymer-based Composite Electrospun Nanofibrous Mats: In vivo Evaluation of Enhanced Burn Wound Healing without Scar Formation.

Researchers aim for new heights in wound healing to produce wound dressings with unique features. Natural, synthetic, biodegradable, and biocompatible polymers especially in the nanoscale are being employed to support and provide efficient wound management. Economical and environmentally friendly sustainable wound management alternatives are becoming an urgent issue to meet future needs. Nanofibrous mats possess unique properties for ideal wound healing. They mimic the physical structure of the natural extracellular matrix (ECM), promote hemostasis, and gas permeation. Their interconnected nanoporosity prevents wound dehydration and microbial infiltration. To prepare and evaluate a novel verapamil HCl-loaded environmentally friendly composite, with biopolymer-based electrospun nanofibers suitable for application as wound dressings providing adequate wound healing with no scar formation. Composite nanofibers were prepared by electrospinning of a blend of the natural biocompatible polymers, sodium alginate (SA) or zein (Z) together with polyvinyl alcohol (PVA). Composite nanofibers were characterized in terms of morphology, diameter, drug entrapment efficiency, and release. In vivo study of the therapeutic efficacy of verapamil HCl-loaded nanofibers on a Sprague Dawley rat model with dermal burn wound was investigated in terms of percent wound closure, and presence of scars. Combining PVA with SA or Z improved the electrospinnability and properties of the developed nanofibers. Verapamil HCl-loaded composite nanofibers showed good pharmaceutical attributes favorable for wound healing including, fiber diameter ∼150 nm, high entrapment efficiency (∼80-100%) and biphasic controlled drug release for 24 h. In vivo study demonstrated promising potentials for wound healing without scaring. The developed nanofibrous mats combined the beneficial properties of the biopolymers and verapamil HCl to provide an increased functionality by exploiting the unique advantages of nanofibers in wound healing at a small dose proved to be insufficient in case of the conventional dosage form.

The Nupower Study: Nuwiq for Perioperative Management of Patients with Haemophilia a on Emicizumab Regular Prophylaxis

Background: Surgery and other invasive procedures have the potential for excessive, uncontrolled bleeding in patients with hemophilia A. Simoctocog alfa (Nuwiq®) has been shown to be highly efficacious at controlling bleeding during and after surgery in hemophilia A patients. Sufficient factor VIII (FVIII) must be available for the surgery and to maintain postoperative coverage. Emicizumab is indicated for the prophylaxis of bleeding in patients with hemophilia A, but additional hemostatic cover may be required to manage bleeding during surgery, particularly major surgeries. To date, there are limited data available on the use of FVIII to provide additional hemostatic cover for surgery in patients on emicizumab. Aims: To evaluate the overall haemostatic efficacy of simoctocog alfa during major surgery in hemophilia A patients on regular emicizumab prophylaxis. Methods: NuPOWER is a prospective, open-label, single-arm, multicenter study to be conducted at approximately 15 study centers worldwide. Previously treated male patients ≥12 years of age with severe hemophilia A (FVIII:C <1%) and no current or past FVIII inhibitors, who have been on regular emicizumab prophylaxis for at least 3 months and scheduled for major elective surgery are eligible for the study. Simoctocog alfa will be administered once within 3 hours prior to surgery and repeated as necessary every 8-24 hours to achieve a FVIII plasma level of 80-100 IU/dL until adequate wound healing has been achieved. Simoctocog alfa dosing will continue for at least another 7 days to maintain a FVIII plasma level of 30-60 IU/dL (Figure 1). The primary endpoint is the overall perioperative hemostatic efficacy ("success" or "failure") of simoctocog alfa. Hemostatic efficacy will be assessed at the end of surgery and at the end of the postoperative period (i.e. up to 24 hours after the last injection of simoctocog alfa), both using an objective 4-point ordinal scale, and adjudicated by the Independent Data Monitoring Committee using a pre-defined algorithm. Secondary endpoints include thrombin generation potential, and incidence of adverse events including thrombotic events and inhibitor formation. Target enrollment is 23 patients to document 26 major surgeries. Each subject can have multiple independent surgeries that will be counted as separate procedures. Study start is planned for Q4, 2022. Conclusions: Results from the NuPOWER study will provide valuable data on the use of simoctocog alfa in patients on emicizumab prophylaxis who need to undergo major surgery. The data will help healthcare professionals to develop evidence-based guidelines for the management of bleeding in hemophilia A patients on emicizumab during surgery. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Nuwiq Dosing and Outcomes in the Management of Women/Girls with Haemophilia a Needing FVIII Treatment for Surgery - an International, Open-Label, Non-Controlled Study (NuDIMENSION)

Background: Historically, hemophilia A has been considered a male disease, leading to a common misconception that carriers are asymptomatic. Hemophilia A carriers have on average half the factor VIII (FVIII) activity (FVIII:C) observed in healthy individuals and they can experience excessive bleeding even with normal FVIII levels. However, bleeding symptoms in women/girls with hemophilia A and in symptomatic carriers are often underrecognized and undertreated. Furthermore, there are limited clinical data available on the management of bleeding in these patients, and improved, evidence-based treatment guidelines on the management of hemophilia A in women/girls are required. Aims: To evaluate the efficacy and safety of the recombinant FVIII simoctocog alfa (Nuwiq®) in women/girls with hemophilia A undergoing major surgery. Methods: NuDIMENSION is a prospective, open-label, single-arm, multicenter study to be conducted at approximately 15 sites worldwide. Women/girls aged ≥12 years of age, diagnosed with moderate or mild hemophilia A (FVIII:C >1% and <40%), scheduled to undergo elective major surgery, and with no current or past FVIII inhibitors are eligible for the study. Simoctocog alfa will be administered once within 3 hours prior to surgery and repeated as necessary every 8-24 hours to achieve a FVIII plasma level of 80-100 international units (IU)/dL until adequate wound healing. Simoctocog alfa dosing will continue for at least another 7 days to maintain a FVIII plasma level of 30-60 IU/dL (Figure 1). The primary endpoint is the overall perioperative hemostatic efficacy ("success" or "failure") of simoctocog alfa in women/girls with hemophilia A undergoing major surgery. Hemostatic efficacy will be assessed at the end of surgery and at the end of the postoperative period (i.e., up to 24 hours after the last injection of simoctocog alfa), both using an objective 4-point ordinal hemostatic efficacy scale, and adjudicated by the Independent Data Monitoring Committee using a pre-defined algorithm. Secondary endpoints include assessment of intra- and postoperative hemostatic efficacy, perioperative FVIII plasma levels, and incidence of adverse events, including inhibitor formation. Target enrollment is 23 patients to document 26 major surgeries. Each subject can have multiple independent surgeries that will be counted as separate procedures. The study is planned to start in Q4 2022. Conclusions: The results from the NuDIMENSION study will contribute to the evidence needed to generate specific treatment guidelines for the management of bleeding in women/girls with hemophilia A undergoing major surgery. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Ninjurin1 Deletion in NG2-Positive Pericytes Prevents Microvessel Maturation and Delays Wound Healing

The formation of mature vasculature through angiogenesis is essential for adequate wound healing, such that blood-borne cells, nutrients, and oxygen can be delivered to the remodeling skin area. Neovessel maturation is highly dependent on the coordinated functions of vascular endothelial cells and perivascular cells, namely pericytes (PCs). However, the underlying mechanism for vascular maturation has not been completely elucidated, and its role in wound healing remains unclear. In this study, we investigated the role of Ninjurin-1 (Ninj1), a new molecule mediating vascular maturation, in wound healing using an inducible PC-specific Ninj1 deletion mouse model. Ninj1 expression increased temporarily in NG2-positive PCs in response to skin injury. When tamoxifen treatment induced a decreased Ninj1 expression in PCs, the neovessels in the regenerating wound margins were structurally and functionally immature, but the total number of microvessels was unaltered. This phenotypic change is associated with a reduction in PC-associated microvessels. Wound healing was significantly delayed in the NG2-specific Ninj1 deletion mouse model. Finally, we showed that Ninj1 is a crucial molecule that mediates vascular maturation in injured skin tissue through the interaction of vascular endothelial cells and PCs, thereby inducing adequate and prompt wound healing.

A randomized phase II study of anlotinib combined with STUPP versus STUPP alone in patients with newly diagnosed glioblastoma (GBM).

TPS2079 Background: Postoperative with radiotherapy, and concomitant and up to 6 cycles of maintenance temozolomide (TMZ) chemotherapy (STUPP regimen) is now the standard treatment for newly diagnosed GBM, while the effectiveness is limited. Anlotinib is a novel, multi-kinase inhibitor against both tumor angiogenesis and tumor cell proliferation with encouraging findings in preclinical GBM models. Our previous single-arm study (NCT04119674) showed that the addition of anlotinb to STUPP exhibited promising progression-free survival (PFS) in patients with GBM. Therefore, a phase II trial was designed to assessed the efficacy and safety of anlotinib with the STUPP regimen. Methods: This is a multicenter, randomized, controlled, phase II superiority trial. Approximately 150 patients will be randomly assigned 1:1 to receive TMZ-based radiochemotherapy with anlotinib or TMZ-based radiochemotherapy with placebo. All patients will receive radiotherapy (fractionated focal irradiation in daily fractions of 1.8–2.0 Gy given 5 days per week for 6 weeks, for a total of 54–60 Gy) concurrently with TMZ (75 mg/m2 QD) and anlotinib (10 mg QD, d1–14/3wks) or placebo. Anlotinib or placebo is administrated during the 28-day treatment break. Adjuvant therapy start four weeks after radiotherapy completion, including six cycles of TMZ (150–200mg/m2, d1–5/4wks) and eight cycles of anlotinib (10 mg QD, d1–14/3wks) or placebo. Patients who complete adjuvant therapy are administrated anlotinib or placebo continuously until the disease progressed or unacceptable toxic effects developed. Eligibility criteria include histologically confirmed newly diagnosed GBM and a World Health Organization (WHO) performance status ≤ 2. Additional inclusion criteria include patients between 18 and 75 years old with adequate wound healing of craniotomy or biopsy; adequate hematologic, hepatic, and renal function; acceptable blood coagulation levels; and the stable or decreasing usage of glucocorticoid doses within 5 days before randomization. Exclusion criteria include potentially fatal intracranial hemorrhage on magnetic resonance imaging (MRI); tumors located only in the brainstem; prior chemotherapy or radiotherapy administered for GBM; and IDH1/2 mutation. The primary objective of this study is to compare PFS accessed by Independent Review Committee in patients receiving anlotinib in addition to standard treatment with patients receiving standard treatment only. Secondary endpoints include overall survival (OS), PFS accessed by investigators, overall response rate (ORR), severity and frequency of AEs (CTCAE V5.0), and quality of life (QOL). The disease control rate (DCR) and duration of response (DOR) will also be explored. Clinical trial information: NCT04959500. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd .

Novel Elastic Threads for Intestinal Anastomoses: Feasibility and Mechanical Evaluation in a Porcine and Rabbit Model.

Gastrointestinal anastomoses are an important source of postoperative complications. In particular, the ideal suturing material is still the subject of investigation. Therefore, this study aimed to evaluate a newly developed suturing material with elastic properties made from thermoplastic polyurethane (TPU); Polyvinylidene fluoride (PVDF) and TPU were tested in two different textures (round and a modified, “snowflake” structure) in 32 minipigs, with two anastomoses of the small intestine sutured 2 m apart. After 90 days, the anastomoses were evaluated for inflammation, the healing process, and foreign body reactions. A computer-assisted immunohistological analysis of staining for Ki67, CD68, smooth muscle actin (SMA), and Sirius red was performed using TissueFAXS. Additionally, the in vivo elastic properties of the material were assessed by measuring the suture tension in a rabbit model. Each suture was tested twice in three rabbits; No major surgical complications were observed and all anastomoses showed adequate wound healing. The Ki67+ count and SMA area differed between the groups (F (3, 66) = 5.884, p = 0.0013 and F (3, 56) = 6.880, p = 0.0005, respectively). In the TPU-snowflake material, the Ki67+ count was the lowest, while the SMA area provided the highest values. The CD68+ count and collagen I/III ratio did not differ between the groups (F (3, 69) = 2.646, p = 0.0558 and F (3, 54) = 0.496, p = 0.686, respectively). The suture tension measurements showed a significant reduction in suture tension loss for both the TPU threads; Suturing material made from TPU with elastic properties proved applicable for intestinal anastomoses in a porcine model. In addition, our results suggest a successful reduction in tissue incision and an overall suture tension homogenization.

Periodontal microsurgery: Magnification and beyond

Background: In clinical dentistry, new heights of precision have taken place with periodontal microsurgery. It enhances visual acuity, improves accessibility with better primary wound closure. Unlike macro surgical procedures, patient acceptance, post operative pain and esthetics were found to be better with the periodontal microsurgery. Microsurgery works on principles like, refinement of motor skills, minimal tissue trauma in order to achieve adequate wound healing. This paper emphasizes widely on the microsurgical concepts used in periodontics.