Innovative Use of an Injectable, Self-Healing Drug-Loaded Pectin-Based Hydrogel for Micro- and Supermicro-Vascular Anastomoses.

Microvascular surgery plays a crucial role in reconnecting micrometer-scale vessel ends. Suturing remains the gold standard technique for small vessels; however, suturing the collapsed lumen of microvessels is challenging and time-consuming, with the risk of misplaced sutures leading to failure. Although multiple solutions have been reported, the emphasis has predominantly been on resolving challenges related to arteries rather than veins, and none has proven superior. In this study, we introduce an innovative solution to address these challenges through the development of an injectable lidocaine-loaded pectin hydrogel by using computational and experimental methods. To understand the extent of interactions between the drug and the pectin chain, molecular dynamics (MD) simulations and quantum mechanics (QM) calculations were conducted in the first step of the research. Then, a series of experimental studies were designed to prepare lidocaine-loaded injectable pectin-based hydrogels, and their characterization was performed by using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and rheological analysis. After all the results were evaluated, the drug-loaded pectin-based hydrogel exhibiting self-healing properties was selected as a potential candidate for in vivo studies to determine its performance during operation. In this context, the hydrogel was injected into the divided vessel ends and perivascular area, allowing for direct suturing through the gel matrix. While our hydrogel effectively prevented vasospasm and facilitated micro- and supermicro-vascular anastomoses, it was noted that it did not cause significant changes in late-stage imaging and histopathological analysis up to 6 months. We strongly believe that pectin-based hydrogel potentially enhanced microlevel arterial, lymphatic, and particularly venous anastomoses.

Neonatal cutaneous melanoma with cutaneous metastasis: a case report and review of literature.

Malignant melanoma, a rare skin cancer in children, primarily affects individuals over 10 years old. Giant congenital nevi, found in about 1% of newborns, increases the risk. However, the development of melanoma from a pre-existing giant congenital nevus diagnosed during the neonatal period is exceptionally rare. We present a case of congenital melanoma in a newborn, where nodules grew on an existing nevus on the baby's back. Literature on managing such cases was reviewed. This case highlights the importance of considering malignant transformation in congenital nevi and the challenges in their management. Due to limited reported cases over 80 years, conclusive findings on survival and treatment options are difficult to provide. Clinicians should report outcomes to develop a management algorithm for neonatal melanoma. Further studies are needed to enhance understanding of causes and treatment for patients with congenital giant hairy nevi and associated melanoma.

Question Mark Ear: An Unusual Anomaly and a Novel Surgical Technique for Reconstruction.

The question mark ear is a rare abnormality characterized by a cleft between the helix and the earlobe, resulting in a protrusion of the upper part of the ear. The severity of this ear malformation can range from a minor notch in the helix to a complete separation of the helix and the earlobe. In this study, we present a case of a patient with a moderately severe right-sided unilateral question mark deformity. To address this issue, we utilized a novel technique that involves a combination of a Y-V flap with double opposing Z-plasty. Our clinical study demonstrates that using this technique for reconstructing the deformity yields excellent results in terms of the helical rim and fold contour, utilizing solely the local tissues.

Morphological, histological and biomechanical comparison of bone marrow aspirate concentrate, micro-fragmented adipose tissue and platelet-rich plasma in prevention of tendon adhesion.

BACKGROUND: Flexor tendon repair often leads to peritendinous adhesions, reducing finger motion and hand function. This study compares the effects of stromal cells from different sources and platelet-rich plasma (PRP) on adhesion formation after tendon repair. METHODS: Forty rabbits had their flexor digitorum profundus tendons transected and repaired with a modified Kessler suture technique. The control group received an isotonic solution. PRP, bone marrow aspirate concentrate (BMAC), and micro-fragmented adipose tissue (MFAT) were injected in groups 2, 3, and 4, respectively. Rabbits wore casts for 2 weeks. Assessments included morphology, histopathology, range of motion (ROM), and biomechanical testing at the 3rd and 8th weeks. RESULTS: At 3 weeks, the BMAC group had the thickest and longest adhesions, the highest Tang Score, and inflammation score. However, at 8 weeks, the BMAC group had the lowest Tang Score and inflammation score. ROM was higher in the PRP group at 3 weeks and BMAC group at 8 weeks. No significant differences were found between BMAC and MFAT groups in adhesion measurements. Biomechanical parameters were higher in BMAC and MFAT groups at 8 weeks compared to control. CONCLUSION: BMAC therapy after primary flexor tendon repair improves adhesion formation and maintains ROM. It also enhances the biomechanical properties of the flexor tendon during the later stages of healing.

Increased Total Antioxidant Capacity Value Improves Survival of Fat Grafts in a Rat Model.

BACKGROUND: While studies aiming to increase fat graft survival continue, in this study, we aimed to investigate the effects of different antioxidants on total antioxidant capacity and their effect on graft survival. METHODS: Thirty-two male Wistar rats were divided into four equally sized groups, including a control group and three antioxidant groups receiving either Melatonin (10mg/kg), Zinc (2mg/kg), or Vitamin E and C (100mg/kg). Autologous fat grafts (1.7± 0.4gr) were transferred to the dorsal subcutaneous region, and total antioxidant capacity was measured on day 0 and 1, week 1 and monthly until the third month. Transferred graft volume and mass (1.3± 0.4gr) were measured using the liquid overflow method and precision scales at the end of the study. Routine hematoxylin-eosin staining and immunohistochemistry against perilipin were performed for semiqualitative analysis and h-score for viable adipose cells, respectively. RESULTS: Collected fat grafts measured significantly less in weight and volume and the survival rate was lower in the control group (p<0.01). Control group exhibited a reduction in TAC, while all groups receiving antioxidants had an increase in TAC during the first week (p=0.02, 0.008, and 0.004 for melatonin, zinc, and vitamins, respectively). Immunohistochemistry of the antioxidant group demonstrated a statistically significant excess and reactivity of cells staining with perilipin antibodies. CONCLUSIONS: In this animal study, the beneficial effect of antioxidants on fat graft survival can be related to the significant increase in TAC following the first week of their administration.

Superior Epididymal Artery-Based Paraepididymal Adipofascial Flap: An Experimental Adipofascial Flap Model in the Rat.

BACKGROUND: Flap surgery is widely performed in reconstructive surgery. Experimental research is vital to improve flap viability. However, the number of flap models for animals is still limited. In this study, we define a new adipofascial flap in rats that can be used to investigate pedicled flap and/or adipofascial flap physiology. METHODS: Eight Wistar male rats were used. Under deep anesthesia, paraepididymal adipofascial flaps were harvested. Flap perfusion was assessed using a near-infrared fluorescence imaging system. The length of the flap and the diameter of the flap pedicle were measured. RESULTS: All animals (n = 8) had sufficient sizes of paraepididymal fat pad, and no animals were lost. The only postoperative complication was testicular hematoma, which was observed in 2 animals. The maximum length of the harvested paraepididymal adipofascial flap was 9.7 cm with a mean of 6.6 cm. The maximum width of the flap was 3.3 cm with a mean of 2.6 cm. The mean pedicle diameter of the paraepididymal adipofascial flap was 1.1 mm. Near-infrared fluorescence imaging revealed adequate perfusion in all flaps. CONCLUSIONS: The number of reported adipofascial flap models in animals is low, and they are mostly limited to flaps based on epigastric vessels. Superior epididymal artery-based paraepididymal adipofascial flap can be used as a pedicled flap model for studies focusing on adipofascial and/or pedicled flap physiology. Uncomplicated surgical technique and short operative time make this flap a valuable alternative to other flap models.

Propeller and Pre-expanded Propeller Use of a Transversely Oriented Upper Trapezius Perforator Flap in Head and Neck Reconstruction: Clinical Experience and Review of Vascular Anatomy of the Supraspinal Trapezius Muscle.

Conventionally, trapezius musculocutaneous flap is raised to harbour perforators located inferior to the scapular spine (i.e. 'lower trapezius flap'). In this clinical study, we aimed to use trapezius perforators located superior to the scapular spine to raise a transversely oriented propeller fasciocutaneous flap based on the superficial cervical artery to reconstruct head and neck defects. Patients with head and neck defects who underwent reconstruction with a propeller trapezius perforator flap between August 2014 and October 2019 were evaluated. Demographic data of the patients, topographic data on defects and the flaps were analysed. A total of 14 patients underwent reconstruction with upper trapezius perforator flap with equal gender distribution. Defects were due to tumour resections, burn contractures and exposed foreign materials; located in occipital, temporal, parietal, midfacial and cervical areas; with sizes ranging between 8 × 7 cm and 22 × 19 cm. Overall patient satisfaction was assessed subjectively using a pre-determined set of questions. The sizes of the flaps ranged between 15 × 8 cm - 20 × 9 cm in non-expanded and 26 × 15 cm - 30 × 16 cm in expanded cases. One flap suffered distal superficial flap loss, which was treated with wound care. Follow up period of the patients ranged between 3 and 40 months with an average of 29 months. Using trapezius perforators located above the scapular spine provides thin transversely oriented propeller flaps to be used in head and neck reconstruction. In our series, this flap is further enhanced by pre-expansion for wider uses, e.g. facial resurfacing and releasing neck contractures.

COX2 inhibition in the treatment of COVID-19: Review of literature to propose repositioning of celecoxib for randomized controlled studies.

Coronavirus-triggered pulmonary and systemic disease, i.e. systemic inflammatory response to virally triggered lung injury, named COVID-19, and ongoing discussions on refining immunomodulation in COVID-19 without COX2 inhibition prompted us to search the related literature to show a potential target (COX2) and a weapon (celecoxib). The concept of selectively targeting COX2 and closely related cascades might be worth trying in the treatment of COVID-19 given the substantial amount of data showing that COX2, p38 MAPK, IL-1b, IL-6 and TGF-ß play pivotal roles in coronavirus-related cell death, cytokine storm and pulmonary interstitial fibrosis. Considering the lack of definitive treatment and importance of immunomodulation in COVID-19, COX2 inhibition might be a valuable adjunct to still-evolving treatment strategies. Celecoxib has properties that should be evaluated in randomized controlled studies and is also available for off-label use.

Risk Assessment of Surgical Interventions Performed on Non-Infected Patients During COVID-19 Pandemic.

Background A number and a variety of surgical interventions were highly affected by the novel coronavirus disease (COVID-19) outbreak. Most of the elective operations were discontinued with the fear of exacerbating the disease in patients and spreading it among healthcare professionals. Objective The objective of this study was to report postoperative rates of COVID-19 in patients who underwent emergency and urgent surgery during the pandemic and to determine a safe algorithm in order to propose an ideal approach for surgeries. Patients and methods A total of 162 patients being operated upon emergency or urgent causes between March 11 and May 31 2020 were included in the study. Safety measures advised by the World Health Organization were applied. The patients' operative data and postoperative COVID-19 status were recorded and statistically evaluated. Results Surgical interventions were required for skin cancer, upper extremity trauma, soft tissue infections, maxillofacial trauma, lower extremity trauma and other causes. Local anesthesia was used for 127 patients (78.4%). General anesthesia was used for 28 patients (17,3%). Two of 162 patients contracted COVID-19 postoperatively on days 15 and 21, respectively. No statistical significance was found between surgery and anesthesia types regarding COVID-19 risk. Conclusion It appears that emergency and urgent surgeries can be performed safely. However, this relies upon adequate safety measures being taken with regards to screening for COVID-19 antigen positivity in patients preoperatively. Further evidence is required to determine the safety of elective surgeries.

Sporadic and Von-Hippel Lindau disease-associated spinal hemangioblastomas: institutional experience on their similarities and differences.

INTRODUCTION: Hemangioblastomas are uncommon tumors of the central nervous system that can be seen in Von Hippel-Lindau (VHL) disease. Despite their benign histology, hemangioblastomas can cause substantial morbidity due to involvement of critical structures. In order to better understand the clinical behavior of spinal cord hemangioblastomas, we have analyzed the clinical, pathologic, radiologic characteristics and management of sporadic and VHL-associated cases at our institution. METHODS: We performed a database search to identify all spinal hemangioblastomas at our institution between 1997 and 2016. Tumor characteristics were analyzed for sporadic and VHL-associated tumors separately in order to understand the differences in groups. RESULTS: We included 20 patients with VHL-associated spinal hemangioblastomas, and 22 patients with sporadic spinal hemangioblastomas. VHL-associated patients were significantly younger at time of presentation compared to sporadic patients (p < 0.0025). Thirty-two patients (76.2%) presented with focal weakness, 34 (81.0%) with sensory loss, and 22 (52.4%) with pain. VHL patients were more likely to present with multiple symptoms (p < 0.001). Median follow-up time was 20.9 months, during which 17 tumors recurred. The median recurrence free interval was 44 months. There were no differences in gross total resection rates between sporadic and VHL-associated cases (p = 0.197). VHL-associated cases had a higher rate of repeat surgery for recurrence (14 patients-73.6%) compared to sporadic cases (3 patients-13.6%; p < 0.001). CONCLUSION: VHL-associated spinal hemangioblastomas differ from sporadic tumors in terms of age, presenting symptoms, multifocality, and rate of recurrence. Recurrences seem to be unrelated to the extent of resection, indicating the need for life-long follow up for VHL patients.

Brain-kidney cross-talk: Definition and emerging evidence.

Cross-talk is broadly defined as endogenous homeostatic signaling between vital organs such as the heart, kidneys and brain. Kidney-brain cross-talk remains an area with excitingly few publications despite its purported clinical relevance in the management of currently undertreated conditions such as resistant hypertension. Therefore, this review aims to establish an organ-specific definition for kidney-brain cross-talk and review the available and forthcoming literature on this topic.

Hypertension as an autoimmune and inflammatory disease.

Hypertension that is considered idiopathic is called essential hypertension and accordingly has no clear culprit for its cause. However, basic research and clinical studies in recent years have expanded our understanding of the mechanisms underlying the development of essential hypertension. Of these, increased oxidative stress, both in the kidney and arterial wall, closely coupled with inflammatory infiltration now appear to have a prominent role. Discovery of regulatory and interleukin-17-producing T cells has enabled us to better understand the mechanism by which inflammation and autoimmunity, or autoinflammation, lead to the development of hypertension. Despite achieving considerable progress, the intricate interactions between oxidative stress, the immune system and the development of hypertension remain to be fully elucidated. In this review, we summarize recent developments in the pathophysiology of hypertension with a focus on the oxidant stress-autoimmunity-inflammation interaction.

Who can get the next Nobel Prize in infectious diseases?

The aim of this paper is to deliver a perspective on future Nobel prizes by reviewing the features of Nobel prizes awarded in the infectious diseases-related (IDR) field over the last 115 years. Thirty-three out of 106 Nobel prizes (31%) in Physiology or Medicine have been awarded for IDR topics. Out of 58 Nobel laureates for IDR topics, two have been female; 67% have been medical doctors. The median age of Nobel laureates in Physiology or Medicine was found to be lower than the median age of laureates in Literature (p<0.001). Since the Second World War, US-affiliated scientists have dominated the Nobel prizes (53%); however before 1945, German scientists did so (p=0.005). The new antimicrobials received Nobel prizes until 1960; however no treatment study was awarded the Prize until the discovery of artemisinin and ivermectin, for which the Nobel Prize was awarded in 2015. Collaborative works have increasingly been appreciated. In the future, more female laureates would be expected in the IDR field. Medical graduates and scientists involved in multi-institutional and multidisciplinary collaborative efforts seem to have an advantage.

Solitary Fibrous Tumor/Hemangiopericytoma Dichotomy Revisited: A Restless Family of Neoplasms in the CNS.

Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) both entered the literature as separate entities in the early to mid 1900s. In contrast to their central nervous system (CNS) counterparts, there has been a tendency to consider these 2 entities as 1 since the early 1990s, as soft tissue SFT gradually included the tumors previously diagnosed as HPC. The most recent World Health Organization (WHO) classification of the tumors of soft tissue considered the term HPC obsolete, and places all such tumors within the extrapleural SFT category. In contrast, CNS SFT and HPC continue to be regarded as different entities in the latest version of the WHO CNS tumor classification. A change in this approach is currently being considered for the upcoming revision of the WHO scheme, but it is not quite clear whether such a change will be as drastic as the one adopted by the soft tissue and bone tumor working group. This article focuses on the historical evolution of these 2 labels as primary CNS neoplasms, and reviews their differences and similarities in terms of clinical, pathologic, and molecular features.