Evaluation of adipose-derived stem cells (ASCS) exosome implantation and platelet-rich fibrin (PRF) on critical long bone defects in Sprague-Dawley rats.

INTRODUCTION: This study aimed to assess the efficacy of adipose-derived mesenchymal stem cell exosomes (ASCs exosome) and platelet-rich fibrin (PRF) in treating critical long bone defects in Sprague-Dawley rats. Critical long bone defects, defined as exceeding 2 cm or 50% of the bone diameter, often pose a healing challenge. While autologous bone grafts have been considered, they have shown unreliable results and donor-site complications, necessitating alternative treatments. METHODS: The research followed a quasi-experimental post-test only control group design involving 30 male Sprague-Dawley rats. The rats were divided into five groups and subjected to femur bone defect creation, internally fixed with a 1.4 mm K-wire, and treated with various combinations of hydroxyapatite (HA), bone graft (BG), ASCs exosome, and PRF. Histomorphometry and BMP-2 gene expression analysis were performed to evaluate bone healing. RESULTS AND DISCUSSION: The results indicated that the group treated with HA + BG + ASCs exosome (group IV) exhibited the highest BMP-2 gene expression, while group III (HA + BG + ASCs exosome + PRF) had the highest chordin level. Overall, groups receiving ASCs exosome or PRF intervention showed elevated BMP-2 expression compared to the control group. The use of ASCs exosome and PRF showed comparable outcomes compared to bone graft administration in terms of histomorphometry analysis. CONCLUSION: The administration of adipose tissue derived mesenchymal stem cells and PRF has a comparable outcome with the use of bone graft in terms of osseus area and expression of BMP-2 in critical bone defect.

The utilization of three-dimensional imaging and three-dimensional-printed model in autologous microtia reconstruction.

Background: The use of three-dimensional (3D) technology helps surgeons in performing autologous microtia reconstruction due to more accurate measurements and a better precision template model. However, the technical aspects of using a 3D imaging and 3D-printed model and the difference in outcomes postoperatively remain poorly reviewed. Purpose: This systematic review aimed to provide the current evidence of the benefit and technical aspects of using 3D technology in autologous microtia reconstruction. Method: A systematic literature search was conducted across multiple databases: Medline, Embase, Google Scholar, and Central until June 2022. Studies that evaluated the use of 3D imaging or 3D-printed models for autogenous microtia reconstruction were selected. The quality of the included studies was also assessed with respect to the study design. Result: A systematic literature search yielded 17 articles with a combination of observational and case report studies. Overall, 3D imaging showed a precise measurement for preoperative costal cartilage assessment. Compared to the 2D template, the utilization of a 3D-printed template provided a higher similarity rate relative to the unaffected ear, higher patient and surgeon satisfaction, and lower surgical time. Most 3D templates were fabricated using polylactic acid material on fused deposition modelling printers. The template costs were ranging from $1 to $4.5 depending on the material used. Conclusion: 3D imaging and 3D-printed templates could improve the outcome of autologous microtia reconstruction. However, the quality of the existing evidence remains low due to the heterogeneity of the reported outcomes. Further studies with more adequate comparability and defined outcomes are still required.

Single stage maxillofacial reconstruction combined radical surgery for managing juvenile ossifying fibroma: A case report.

Ossifying fibroma (OF) in craniofacial is a rare disease, benign, locally aggressive fibro-osseous tumor. The 2017 World Health Organization classifications divided OF into two types: OF of odontogenic origin and juvenile ossifying fibroma (JOF). Determining the right surgical treatment to reduce the postoperative recurrence rate is incredibly challenging. The author reports two cases of paranasal sinuses with disease onset progressed from pre-pubertal age. The first case is an example of a recurrent case after undergoing conservative surgery, and the second is a new one. All cases underwent radical surgery with subtotal maxillectomy and reconstructive surgery in one stage. After observing all patients until one year, there was no sign of recurrence through clinical and endoscopic examination. There are two types of surgery that compare in this case report: conservative surgery and radical surgery. Conservative surgical procedures include curettage, enucleation, or peripheral osteotomies. Several studies have shown high recurrence levels in OF patients when curettage or enucleation is performed; residue caused by incomplete excision is the most common reason that is easily caused by conservative surgery. Radical surgery such as open maxillectomy is a promising approach for degrading the level of recurrence. JOF, especially trabecular juvenile ossifying fibroma, shows a high recurrence percentage comparing other types. The first-choice management for treating OF was the surgical approach. Types of surgery depend on the disease's aggressiveness and morbidity. Radical surgery was proven better at decreasing recurrence level than conservative surgery.

Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial.

Wound healing in DFU (diabetic foot ulcer) has prolonged inflammation phase and defective granulation tissue formation. LL-37 has antimicrobial property, induces angiogenesis, and keratinocyte migration and proliferation. This study analyzes the efficacy of LL-37 cream in enhancing wound healing rate and decreasing the levels of IL-1α, TNF-α, and the number of aerobic bacteria colonization in DFU with mild infection. This study was conducted from January 2020 to June 2021 in Jakarta. Subjects were instructed to apply either LL-37 cream or placebo cream twice a week for 4 weeks. Wounds were measured on days 7, 14, 21, and 28 and processed with ImageJ. The levels of LL-37, IL-1α, and TNF-α from wound fluid were measured using ELISA. The number of aerobic bacteria colonization was counted from the isolate grown in culture. The levels of LL-37 in DFU at baseline were equally low in both groups which were 1.07 (0.37-4.96) ng/mg protein in the LL-37 group and 1.11 (0.24-2.09) ng/mg protein in the placebo group. The increase in granulation index was consistently greater in the LL-37 group on days 7, 14, 21, and 28 (p = 0.031, 0.009, 0.006, and 0.037, respectively). The levels of IL-1α and TNF-α increased in both groups on days 14 and 21 (p > 0.05). The decrease in the number of aerobic bacteria colonization was greater in the LL-37 group on days 7, 14 and 21, but greater in the placebo group on day 28 (p > 0.05). In conclusion, LL-37 cream enhanced the healing rate of DFU with mild infection, but did not decrease the levels of IL-1α and TNF-α and the number of aerobic bacteria colonization. This trial is registered at ClinicalTrials.gov, number NCT04098562.

Desentrañando la sinfonía genética y epigenética: una revisión narrativa sobre la interacción en la etiología de la microtia / Unravelling the genetic and epigenetic symphony: a narrative review exploring the interplay in etiology of microtia

La microtia, una anomalía congénita del oído externo, sirve como modelo para explorar la compleja sinergia entre la genética y la epigenética en la determinación de resultados fenotípicos. La genética, que reside en el ADN, proporciona el plano para el desarrollo, mientras que las modificaciones epigenéticas modulan la expresión génica sin alterar la secuencia del ADN. Esta revisión exhaustiva se adentra en su influencia combinada sobre la etiología de la microtia, desentrañando la importancia de la metilación del ADN, las modificaciones de las histonas y los microARNs en la formación del oído y su susceptibilidad a las señales ambientales. Las investigaciones genéticas incluyen análisis de pedigrí y secuenciación del exoma completo, destacando genes esenciales como HOXA4 y CHST15. Las asociaciones sindrómicas subrayan la base genética multifacética de la microtia. Esta interacción dinámica entre la genética y la epigenética enriquece nuestro entendimiento de las anomalías del desarrollo, ofreciendo perspectivas para intervenciones a medida y estrategias clínicas para manejar esta condición de manera personalizada. La continua exploración de estas interacciones abre caminos para descifrar procesos de desarrollo complejos y expandir nuestra comprensión de anomalías relacionadas. (AU)

Microtia, a congenital anomaly of the external ear, serves as a model to explore the intricate synergy between genetics and epigenetics in shaping phenotypic outcomes. Genetics, residing in DNA, provides the blueprint for development, while epigenetic modifications modulate gene expression without altering the DNA sequence. This comprehensive review delves into their combined influence on microtia’s etiology, unravelling the significance of DNA methylation, histone modifications, and microRNAs in ear formation and their susceptibility to environmental cues. Genetic investigations encompass pedigree analysis and whole-exome sequencing, spotlighting pivotal genes like HOXA4 and CHST15. Syndromic associations underscore the multifaceted genetic underpinning of microtia. This dynamic interplay between genetics and epigenetics enriches our understanding of developmental anomalies, offering insights for tailored interventions and clinical strategies to manage this condition in a personalized manner. The continuous exploration of these interactions opens avenues for deciphering intricate developmental processes and expanding our comprehension of related anomalies. (AU)

The effect of plastic tape seal to reduce face seal leak in respirator N-95 type 1860.

The risk of face seal leak while using N-95 respirators is experienced by health workers and thus failing fit test are quite common. Finding solutions to overcome face seal leaks is crucial; one of which is by sealing the N-95 respirator. The seal used in this research was Tegaderm® a transparent film dressing or a plastic tape which is known to have the advantages of strong adhesion, high level of pore density and standardized medical grade. This study tries to determine the effectiveness of plastic tape adhesive on the N-95 type 1860 respirator in overcoming face seal leak qualitative fit test using Bitrex immediately after being worn and after 4 h of using it. The study used a quantitative approach with an incidence study design conducted pre and post experimental without comparison to see the effectiveness of plastic tape sealing. The subjects for the research were 81 health workers in the CMH environment who were at risk of being exposed to COVID-19. The study found a significant difference in the Bitrex fit test immediately after sealing the N-95 type 1860 respirator with plastic tape; 100% passed the fit test immediately after sealing, and 64.2% passed the fit test after 4 h of working. The effectiveness of sealing using plastic tape is considered to be quite good to overcome face seal leak on the N-95 type 1860 respirator. Health care workers need to be more vigilance to ensure better face seal.

Cross-sectional study on the proportion of smell and taste disturbances in hospitalized COVID-19 patients.

BACKGROUND: The number of confirmed Coronavirus Disease-2019 (COVID-19) cases in Indonesia had reached 1.4 million cases from a total population of 270 million. Smell and/or taste disturbances are frequently found as early symptoms of COVID-19 patients. Our study aimed to investigate the proportion and characteristics of anosmia and/or ageusia in COVID-19. MATERIALS AND METHODS: This cross-sectional study identifies the proportion and severity of smell and taste disturbances in COVID-19 patients. Subjects were recruited by consecutive sampling. All subjects were required to fill in the questionnaire modified from the American Academy of Otolaryngology-Head and Neck Surgery Anosmia Reporting Tool (AAO-HNS ART). Symptoms severity was measured with a numerical rating scale of 0-10; 0-3 is defined as mild, 4-6 as moderate, and 7-10 as severe. RESULTS: Out of 51 subjects, 34 (66.7%) suffered from smell and/or taste disturbances. Twenty-nine of 34 subjects (85.3%) suffered from smell disturbance, and 24 of 34 subjects (70.5%) suffered from taste disturbance. Severe smell disturbance occurred in 68.9% of subjects, while severe taste disturbance occurred in 50%. The median onset was three days for smell disturbance and four days for taste disturbance after any symptoms of COVID-19. CONCLUSION: Smell and/or taste disturbances were early symptoms of COVID-19. These symptoms commonly occurred within the first four days of clinical onset and frequently manifested in severe conditions.

The role of VEGF, PDGF and IL-6 on diabetic foot ulcer after Platelet Rich Fibrin + hyaluronic therapy.

BACKGROUND: Current standard management of diabetic foot ulcers (DFUs) consists of surgical debridement followed by soak NaCl 0.9% gauzes tight infection and glycaemic control. Nowadays the use of advanced platelet-rich fibrin (A-PRF) has emerged as an adjunctive method for treating DFUs. This study was conducted to demonstrate the ability of combine A-PRF + HA as a complementary therapy in DFUs healing related with angiogenesis,inflammation and granulation index process. METHODS: This open label randomized controlled trial was conducted in Koja District Hospital and Gatot Soebroto Hospital Jakarta, Indonesia on July 2019-April 2020. DFUs patients with wound duration of three months, Wagner-2, with size of ulcer less than 40 cm2 were included in the study. The number of subjects was calculated based on the rule of thumb and allocated randomly into three groups, namely topical A-PRF + HA, A-PRF and Sodium Chloride 0.9% as a control, for each of 10 subjects. A-PRF made by 10 mL venous blood, centrifuge 200 G in 10 min, meanwhile A-PRF + HA though mix both them with vertex machine around 5 min. Biomarker such as VEGF, PDGF and IL-6 examined from DFU taken by cotton swab and analysis using ELISA. Granulation Index was measured using ImageJ. Biomarkers and granulation index were evaluated on day 0, 3, 7 and 14. Data were analysed using SPSS version 20 with Anova and Kruskal Wallis test to compare the angiogenesis and inflammation effect between the three groups. RESULT: In topical dressing A-PRF + HA, there is an increase in delta VEGF on day-3 (43.1 pg/mg protein) and day-7 (275,8 pg/mg protein) compared to A-PRF on day-3 (1.8 pg/mg protein) and day-7 (104.7 pg/mg protein), also NaCl (control) on day-3 (-4.9 pg/mg protein) and day-7 (28.3 pg/mg protein). So that the delta VEGF of A-PRF + HA group increase significantly compared with others on day-3 (p = 0.003) and day- 7 (p < 0.001). Meanwhile A-PRF + AH group, there is also a decrease in delta IL-6 after therapy on day-3 (-10.9 pg/mg protein) and day-7 (-18.3 pg/mg protein) compared to A-PRF in delta IL-6 on day- 3 (-3.7 pg/mg protein) and on day-7 (-7.8 pg/mg protein). In NaCl (control) group there is a increase delta IL-6 on day-3 (4.3 pg/mg protein) and on day-7 (35.5 pg/mg protein). So that the delta IL-6 of A-PRF + HA group decrease significantly compared with others only on day- 7 (p = 0.015). In PDGF le level analysis, A-PRF + HA group increase significantly (p = 0.012) only in day -7 compare with other group (5.5 pg/mg protein). CONCLUSION: The study shows the superior role of combined A-PRF + HA in the treatment DFU though increase angiogenesis and decrease inflammation pathway. The advantage of using A-PRF + HA is that it accelerates wound healing by increasing granulation tissue compared to A-PRF alone.

A Modified Preparation Method of Ideal Platelet-Rich Fibrin Matrix From Whole Blood.

One bioproduct that is widely used in the wound healing process is platelet-rich plasma (PRP). PRP is a liquid solution with high autologous platelet concentration, making it a good source of growth factors to accelerate wound healing. Recent development in PRP had created a new product called platelet-rich fibrin matrix (PRFM), which has a denser and more flexible structure. PRFM is the newest generation of platelet concentrate with a fibrin matrix that holds platelet in it. The key concept in creating PRFM from PRP is the addition of CaCl2 followed by centrifugation, which converts fibrinogen to fibrin, and the fibrin cross-links to form a matrix that contains viable platelets. There are many commercially available kits to create PRFM, but they are often expensive and uneconomical. This research will test a modified method of making ideal PRFM from PRP without any commercial kits. The modified method will include determining the minimum level of CaCl2 used, the type of centrifuge, and the speed and duration of centrifugation. By performing a modified preparation method on five samples of whole blood, it was found that the ideal PRFM could be made by mixing PRP with 25 mM CaCl2 and centrifuging it at a speed of 2,264 × g for 25 min at room temperature. The PRP and PRFM platelet counts of this method tend to be lower than the platelet counts found in other studies. Although visually comparable, further study is needed to compare the performance of PRFMs made with this method and PRFMs made with commercial kits.

Comparison between PRP and PRFM on FTSG healing profile: Macroscopic, microscopic and ELISA evaluation.

BACKGROUND: Studies had shown the benefit of PRFM and PRP in wound healing but their use in skin graft healing was rarely studied. This study aims to compare the use of PRP and PRFM in accelerating wound healing process of skin full-thickness skin graft (FTSG). MATERIALS AND METHODS: Five pigs were used to look at the wound healing effect of PRP and PRFM usage prior to FTSG implantation. Subsequent punch biopsies were then conducted on the 1st, 3rd, 7th, 14th, and 30th day to obtain samples for macroscopic (skin color), extracellular matrix (collagen), microscopic (PMN, macrophage, and fibroblast), and ELISA (TGFß1 and PDGF) analysis to determine the level of wound healing activity. ImageJ software was used to photograph for macroscopic and extracellular matrix analysis. RESULTS: Macroscopic, extracellular matrix, and ELISA evaluation show no significant difference in FTSG survival rates for all treatment groups. Microscopic examination showed an increase in PMN, macrophage, and fibroblast levels with PRFM application showing higher increases in all observed microscopic variables compared to PRP and control. CONCLUSION: This study observed that both PRFM and PRP as autologous platelet preparation accelerate wound healing in FTSG, with PRFM being superior due to the higher number of PMN, macrophage, and fibroblast.

Multiple Approaches for Managing Complex Ophthalmic Blunt Trauma: A Case Report.

INTRODUCTION: Ophthalmic trauma is defined as injuries affecting the ocular structures, including the globe, eyelid, lacrimal system, and surrounding orbital walls. Blunt trauma acts as the leading cause of injury and it may affect both the anterior and posterior parts of the globe. Prompt diagnosis, early management, and sustained follow-up are mandatory for an optimal outcome. PURPOSE: This report presents a one-step surgery management process for an intricate case of blunt facial trauma with complex ophthalmic and nasal injury. PATIENTS AND METHODS: A 45-year-old male with blunt force trauma of the left eye from a wooden block, suffered from naso-orbital-ethmoidal fractures, eyelid laceration with canalicular, close-globe injuries of traumatic cataract and vitreous hemorrhage with retinal detachment. A simultaneous one-step surgery was performed by a trauma team of ophthalmological and ENT surgeons during the height of the COVID-19 pandemic to lessen the risk of cross-transmission. After ruling out the possibility of open-globe rupture, traumatic cataract extraction, retinal detachment surgery, the repair of an eyelid laceration with canalicular involvement, and septorhinoplasty were performed on concomitantly. RESULTS: Anatomical success was achieved for the repair of the nasoorbitoethmoidal (NOE) type II fracture and close-globe injuries, including the anatomical reattachment of the retina. However, the functional outcome remained unsatisfactory. Visual acuity failed to show further improvement at a later follow-up. Traumatic optic neuropathy was, at the final follow-up, considered to be the cause of the suboptimal visual acuity. CONCLUSION: A single-step multi-procedure for a complex ophthalmic blunt trauma, as demonstrated in this case, may be beneficial for reducing the complications that might arise due to treatment delay. The complex nature of the injury, however, creates the higher possibility for residual post-operative complications. Risks of residual functional impairment should be considered in such complex trauma prior to surgery, to determine the surgical prognostic value and provide appropriate consent to the patient.

Platelet-Rich Fibrin Enhances Surgical Wound Healing in Total Laryngectomy.

Autologous growth factor (AGF) is a cytokine that has gained medical research interest because it helps improve and accelerate the wound healing process. Platelet-rich fibrin (PRF) is the latest generation of platelet concentrate that can be obtained through a simple procedure known as AGF referencing. One of the most common complications of total laryngectomy (TL) is pharyngocutaneous fistula. To prevent this complication, health care providers must closely monitor the postoperative wound healing process.This study aimed to investigate the effectiveness of PRF application in enhancing wound healing after TL. A randomized controlled trial was conducted in the Department of Otorhinolaryngology - Head and Neck Surgery, Faculty of Medicine, Dr. Cipto Mangunkusumo Hospital Universitas Indonesia, Jakarta, Indonesia, from June 2019 to December 2019. We included 20 patients who underwent TL for laryngeal squamous cell carcinoma. They were divided into two groups (10 patients who received applied autologous PRF around the esophageal stoma during TL and another 10 patients as the control). These patients were observed for 2 weeks postoperatively. In the bivariate analysis performed using the chi-square test, the pain threshold and edema of postoperative wounds in the PRF-treated group demonstrated significant differences compared with those in the control group. PRF application in TL enhanced the postoperative wound healing process, especially with regard to edema and pain.

PRFM enhance wound healing process in skin graft.

Facial plastic and reconstructive surgery often used skin graft on defects that cannot be covered primarily by a local flap. However, wound healing using skin graft is slow, most of the time the graft is contractured and the take of graft is not optimal. Platelet rich fibrin matrix (PRFM) is a new generation of concentrated platelets that produce natural fibrin and reported to speed up the healing process. Application of PRFM in the skin graft implants is expected to increase the survival of the graft. We used porcine as animal models to elucidate the effect of autologous PRFM on wound healing in full-thickness (FTSG) and split-thickness (STSG) skin grafts. Survival level of the skin graft was determined by using ImageJ software based on the formation of collagen type 1 and graft take. We observed that the use of PRFM in FTSG and STSG increased type 1 collagen formation. We also found that PRFM addition in STSG gave the best skin graft take.