Effectiveness of autologous fibrin glue in preventing post-thoracotomy air leaks: a randomized controlled trial.

Introduction: Post-thoracotomy air leaks remain a significant challenge in thoracic surgery. Aim: This randomized controlled trial assessed the efficacy of autologous fibrin glue in reducing air leaks following thoracotomy procedures. Material and methods: Conducted as a single-center, single-blind, randomized clinical trial, the study enrolled adult patients undergoing lung resection or decortication at a thoracic surgery clinic. Participants were randomly assigned to either the intervention group, receiving autologous fibrin glue application during surgery, or the control group, undergoing standard surgical procedures without glue application. Key inclusion criteria were adult patients undergoing elective thoracotomy for lung resection or decortication, while exclusion criteria included patients with severe comorbidities or contraindications to fibrin glue. Results: A total of 40 patients were enrolled and randomized equally to the two groups. The group treated with autologous fibrin glue demonstrated a significant reduction in the duration of air leakage and chest tube drainage, along with a shorter hospital stay, compared to the control group. There were no statistically significant differences in postoperative complications between the groups. Conclusions: The application of autologous fibrin glue during thoracotomy procedures significantly reduces postoperative air leaks and hospitalization duration without increasing complication rates. This finding suggests a beneficial role of fibrin glue in thoracic procedures requiring lung resection or decortication.

Treatment of recalcitrant esophagocutaneous fistula by platelet-rich-plasma-fibrin glue: A case study.

INTRODUCTION: Recalcitrant esophagocutaneous fistula is a very uncommon complication after neck surgery. Management of this non-healing fistula has long been a topic of debate. This report provides an approach for treating it. PRESENTATION OF CASE: A 65-year-old woman presented nineteen years after branchial cleft cyst surgery with cyst recurrence associated with swelling. Sonography displayed a collection in the front of the left carotid artery in the suprasternal notch. On the CT, a similar finding was seen, a collection with gaseous density in front of the left sternocleidomastoid and a hypodense nodule on the right lobe of the thyroid. The pathology report describes an abscess with many macrophages and neutrophils, fat necrosis, microcalcification, and foreign body reaction around amorphous bodies. Again, surgical resection of the swelling area and tract was done and an esophago-cutaneous fistula was developed after surgery which did not heal after 6 months. CLINICAL DISCUSSION: According to accelerating the healing time and complete closure of chronic wounds such as lower-extremity diabetic ulcers, persistent pneumothorax, anal fistula, and recalcitrant gastrocutaneous fistula by using platelet-rich plasma (PRP) and fibrin glue (FG); PRP-FG can be considered as a safe and effective treatment option for chronic wound healing. So, for treatment of this fistula, PRP-FG was used. PRP-FG was obtained from the patient's blood and injected into the fistula tract. The discharge was stopped after one week and the fistula was cured. CONCLUSION: PRP-FG injection into the fistula tract provides a simple and non-invasive approach for the treatment of recalcitrant esophagocutaneous fistula.

Persistent pneumothorax treatment following congenital cardiac surgery by platelet-fibrin glue.

Persistent pneumothorax is a life-threatening complication that can occur after congenital cardiac surgery. Traditional treatment such as chest tube drainage may not be effective in managing this condition. This study presents a new minimally invasive method for treating persistent pneumothorax using platelet-rich plasma-fibrin glue (PRP-FG). The method has been successful in treating postoperative chylothorax in previous studies, and its use has decreased morbidity, mortality, and hospital stay in chylothorax patients. Ten patients with persistent pneumothorax following cardiothoracic surgery (3 TAPVC, 2 d-TGA, 2 VSD + IAA,1 TRUNCUS + TAPVC, 1 VSD + COA, 1 GLENN), who did not respond to conservative management, underwent treatment with PRP-FG. Follow-up was done for a period of 1-4 years. The age and diagnoses of pneumothorax after surgery were 85.5 ± 36.0 days and 62.4 ± 34.3 h, respectively. Persistent pneumothorax of 8 patients (80%) was cured completely after PRP-FG injection. PRP-FG therapy was failed in two patients who died. All cured patients had a normal life without any complications during follow-up. After PRP-FG injection, 3 patients stopped bubbling at one-time injection, 3 patients stopped bubbling at two-time injection, and 2 patients stopped bubbling at three-time injection. Two patients died during treatment; in these cases, one-time injections were done which was not successful. Persistent pneumothorax after congenital-cardiac surgery can be treated successfully with PRP-FG. This bedside minimal-invasive procedure may significantly decrease the morbidity and mortality rate. Further research is needed to confirm the efficacy of this promising treatment through multicentre clinical trials.

The Potential of Leucomethylene Blue in Methemoglobinemia Treatment: A New Hope for Patients with G6PD?

Methylene blue (MB) has been routinely used to treat methemoglobinemia. In the body, MB is reduced to leucomethylene blue (LMB) by NADPH-dependent methemoglobin (MetHB) reductase, and then LMB reduces Fe3+ to Fe2+. In glucose-6-phosphate dehydrogenase (G6PD) deficiency, NADPH is not produced sufficiently to protect erythrocytes against oxidative stress and to take part in relevant biochemical reactions. Since MB is an oxidative agent, its administration in individuals with G6PD deficiency leads to an increased risk of hemolysis through oxidative stress and even death. Therefore, its administration has been prohibited from treating methemoglobinemia in G6PD patients. As an antioxidant and direct reducing agent for Fe3+, LMB may be prescribed for treating MetHB in patients with G6PD deficiency. Considering the biochemical process of turning MB into LBM and the reducing nature of LMB, it seems LMB is a safer drug than MB in treating methemoglobinemia. LMB can even be administrated in other treatments without any concern about increasing oxidative stress, exacerbating the inflammation. Proof-of-concept experimental and clinical trials could substantiate this hypothesis.

Combined use of platelet-rich plasma and adipose tissue-derived mesenchymal stem cells shows a synergistic effect in experimental spinal cord injury.

Spinal cord injury (SCI) as a crippling disability causes tissue degeneration via neuron loss and fiber disruption. Some researchers have tried to reverse or minimize these changes. Platelet-rich plasma (PRP) is a biological product derived from peripheral blood containing a variety of growth factors. PRP has been extensively used in regenerative medicine. On the other hand, via secreting neuroprotective growth factors, mesenchymal stem cells (MSCs) have shown a promising potential in repairing central nervous system deficits. This study investigated the therapeutic effect of the combined use of MSCs and PRP in a rat model of SCI. We used real time-PCR method for evaluation of Bcl-2, Bax and caspase 3 expressions, TUNEL test for apoptotic cell death assessment, and neurofilament NF200 immunohistochemistry for examination of axonal regeneration. The results showed that co-treatment with MSCs and PRP efficiently alleviated the evaluated categories. Significant differences were observed in expression of Bcl-2 and caspase3, but not Bax, apoptotic index and the number of NF200 positive axons (for all P ≤ 0.01) between co-treatment animals compared with those treated with only MSCs or PRP. In conclusion, this study showed that combination of MSCs and PRP synergistically promotes their therapeutic effects in the SCI.

Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial.

COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients' lives. Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C-N-acetyl Cysteine (MCN). Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. In conclusion, NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases. TRIAL REGISTRATION NUMBER: NCT04370288.

Autologous Platelet-Rich Plasma and Fibrin Glue Decrease Pain Following Excision and Primary Closure of Pilonidal Sinus.

BACKGROUND: Pilonidal sinus is one of the most complicated chronic wounds common in younger adults. This disabling condition affects the natal clefts of the buttocks and often requires surgery. OBJECTIVE: To investigate the effect of autologous platelet-rich plasma and fibrin glue (PRP-FG) on pain reduction and the healing process of pilonidal sinus after excisional surgery with primary closure. METHODS: This randomized clinical trial study included 40 patients with pilonidal sinus admitted to a surgical ward. Patients were randomly divided into two groups: the control group, who underwent wide excision of the sinus with primary closure, and the case group, who had wide excision of the sinus with primary closure along with injection of autologous PRP-FG into the wound. For 6 months, patients were followed up for their severity of pain, wound healing process, the time it took them to get back to normal activities, infection, and other complications. RESULTS: In the first and second week after surgery, the severity of pain in the case group was reduced significantly in comparison with the control group. Healing time decreased but not significantly. There was no significant difference in infection and recurrence between the two groups. CONCLUSIONS: The addition of PRP-FG has the potential to reduce pain significantly in primary closure of pilonidal sinus.

Novelty in limbal stem cell culture and cell senescence.

Limbal stem cell deficiency is a pathological state. Recently, limbal stem cell (LSC) transplantation has attracted great interest as a therapeutic method which mainly involves in-vitro expansion of LSCs. It is believed that ex-vivo cultivation conditions could affect the outcome of surgery and the rate of successful transplantation. Thus, we aimed to define a suitable culture condition by conducting a research on ex-vivo expanded LSCs to maintain an optimized graft of amniotic membrane with cultivated-limbal stem cells, regarding the quantity and quality, with the hope of improving the clinical outcome.

Efficacy and Safety of Pleurodesis Using Platelet-Rich Plasma and Fibrin Glue in Management of Postoperative Chylothorax After Esophagectomy.

INTRODUCTION: Chylothorax is by definition a collection of lymphatic fluids in the pleural cavity because of leakage from main thoracic duct or its tributaries. It is an uncommon but serious postoperative complication in esophageal cancer patients. There is no standard therapeutic algorithm for chylothorax because no prospective or randomized trials have yet been performed to evaluate the available treatment options. The aim of this study was to evaluate the efficacy of pleurodesis with a combination of platelet-rich plasma (PRP) and fibrin glue to the treatment of chylothorax after trans-hiatal esophagectomy. MATERIALS AND METHODS: We randomly allocated 52 consecutive esophageal cancer patients with postoperative chylothorax who did not respond to conservative management to either PRP fibrin glue pleurodesis or surgical thoracic duct ligation. 26 patients in each group were treated with PRP fibrin glue pleurodesis or surgical thoracic duct ligation in order to control chylothorax. Perioperative data, including success rate and complications of both interventions, were analyzed. RESULTS: Two groups were similar in terms of patients' demographics and tumor characteristics. All 26 patients in pleurodesis group (100%) and 20 patients in surgery group (76.9%) were successfully treated (p = 0.009). Seven patients (26.92%) in pleurodesis group required a second application of PRP fibrin glue after a week. The mean length of hospital stay was 53.50 ± 16.662 days in surgery group and 36.04 ± 8.224 days in pleurodesis group (p < 0.001). Although mortality rate in surgery group was higher than pleurodesis group, it was not statistically significant (p = 0.1621). There was no significant difference in complications between two groups either. No serious side effect occurred with PRP fibrin glue application. CONCLUSION: In conclusion, pleurodesis using PRP and fibrin glue for chylothorax after trans-hiatal esophagectomy was associated with significantly increased success rate, decreased ICU stay, decreased overall hospital stay, and decreased mortality compared with surgical thoracic duct ligation. No patient after PRFG required additional intervention including surgery. Thus, given the improved outcomes with PRFG pleurodesis, this technique may be considered in all patients with postoperative chylothorax after or during conservative management and before proceeding to more invasive interventions.

Comparison of autologous fibrin glue versus nylon sutures for securing conjunctival autografting in pterygium surgery.

PURPOSE: To compare the safety, operating time, postoperative ocular signs, symptoms, overall patient satisfaction, complications rate and recurrence rate of autologous fibrin glue (AFG) and nylon suturing (NS) for attaching conjunctival autografts in pterygium surgery. METHODS: A prospective, randomized, interventional study was performed among 120 patients (120 eyes) with primary pterygium. Superior conjunctival autograft was harvested and transferred on to bare sclera after pterygium excision. For attaching the autograft, AFG (n = 60 eyes) and NS (n = 60 eyes) were used. The patients were followed up for 12 months. The groups were compared for the safety, operative time, postoperative ocular signs, symptoms, overall patient satisfaction, recurrence and complications rate. RESULTS: All conjunctival autografts in both groups were successfully attached. The average operating time for the AFG group was significantly shorter (P < 0.001). Postoperative symptoms were fewer for the AFG group than the suture group. After 12 months of follow-up, no recurrence was reported for the AFG group, but 8.3% of patients experienced recurrence in the NS group. CONCLUSIONS: Our study demonstrated the superiority of AFG to NS in saving operating time and elimination of recurrence without any complications in pterygium surgery. AFG can obviate the need for suturing and increases the viability of tissue flaps. Additional studies are necessary to determine the long-term effects considering factors such as primary or recurrent status of pterygium, age and sex of patient, dose and duration of treatment for mitomycin C.

Platelet rich plasma: Effective treatment for repairing of spinal cord injury in rat.

OBJECTIVE: The aim of the present study was to evaluate the effect of PRP on the repair of spinal cord injury in rat model. MATERIAL AND METHODS: Rats were randomly divided into three groups with six rats in each group. Then, spinal cord injury was performed under general anesthesia using "weight dropping" method. Control group included rats receiving normal saline, group two received PRP 1 week after injury; group three received PRP 24 h after injury. The motor function was assessed weekly using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. Anterograde tracing was performed for evaluation of axon regeneration. RESULT: Motor recovery was significantly better in the rats treated with PRP 24 h after injury than the control group. In the rats treated with PRP 1 week after injury and rats treated with PRP 24 h after injury, the average numbers of BDA-labeled axons were statistically different from the control group. CONCLUSION: Our experimental study demonstrated positive effects of platelet rich plasma on nerve regeneration after spinal cord injury.

Success of Maxillary Alveolar Defect Repair in Rats Using Osteoblast-Differentiated Human Deciduous Dental Pulp Stem Cells.

PURPOSE: The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response in craniofacial abnormalities. The main aim of this study was to evaluate the regenerative potential of human dental pulp stem cells, isolated from deciduous teeth, for reconstructing maxillary alveolar defects in Wistar rats. MATERIALS AND METHODS: Human deciduous dental pulp stem cells were isolated and stimulated to differentiate into osteoblasts in culture media. Maxillary alveolar defects were created in 60 Wistar rats by a surgical procedure. Then, on the basis of the type of graft used to repair the bone defect, the rats were divided into 6 equal groups: groups 1 and 2, transplantation of iliac bone graft; groups 3 and 4, transplantation of stem cells derived from deciduous dental pulp in addition to collagen matrix; groups 5 and 6, transplantation of just collagen matrix. Then, fetal bone formation, granulation tissue, fibrous tissue, and inflammatory tissue were evaluated by hematoxylin-eosin staining at 1 month (groups 1, 3, and 5) and 2 months (groups 2, 4, and 6) after surgery, and data were analyzed and compared using the Fisher exact test. RESULTS: Maximum fetal bone formation occurred in group 2, in which iliac bone graft was inserted into the defect area for 2 months; there also were significant differences among the groups for bone formation (P = .009). In the 1-month groups, there were no significant differences between the control and stem cell-plus-scaffold groups. There were significant differences between the 2-month groups for fetal bone formation only between the control and scaffold groups (P = .026). CONCLUSIONS: The study showed that human dental pulp stem cells are an additional cell resource for repairing maxillary alveolar defects in rats and constitute a promising model for reconstruction of human maxillary alveolar defects in patients with cleft lip and palate.

Pro-oxidant-antioxidant balance in Iranian veterans with sulfur mustard toxicity and different levels of pulmonary disorders.

OBJECTIVE: Sulfur mustard (SM) is a strong alkylating agent that primarily targets the skin, eye and lung. The current study evaluated the pro-oxidant-antioxidant balance (PAB) assay in human serum of SM-exposed patients. DESIGN AND METHODS: sera of 35 SM-exposed patients and 19 healthy volunteers were recruited. Both groups had nonsmoker and nonalcoholic people with no diseases such as diabetes, heart disease and other pulmonary diseases (COPD because of smoking, asthma and so on). All patients had documented exposure to SM. The PAB was measured. RESULTS: SM-exposed patients with normal values for pulmonary function test and severe obstructive pulmonary disease demonstrated a significant increase in PAB value in compared with healthy volunteers (the PAB values in healthy volunteers, normal and severe patients were 48.74 ± 21.07 HK, 101.45 ± 32.68 HK and 120.23 ± 31.55 HK, respectively). However, the level of oxidation is not related to the severity of disease defined by spirometry findings. A significant negative correlation was established between the PAB value and FEV1. CONCLUSIONS: The increased PAB value in chemical casualties showed that these patients are exposed to oxidative stress.

Differentiation of adipocytes and osteocytes from human adipose and placental mesenchymal stem cells.

OBJECTIVES: Mesenchymal stem cells (MSC) can be isolated from adult tissues such as adipose tissue and other sources. Among these sources, adipose tissue (because of easy access) and placenta (due to its immunomodulatory properties, in addition to other useful properties), have attracted more attention in terms of research. The isolation and comparison of MSC from these two sources provides a proper source for clinical experimentation. The aim of this study was to compare the characteristics of MSC isolated from human adipose tissue and placenta. MATERIALS AND METHODS: Adipose and placental MSC were isolated from the subcutaneous adipose tissues of 10 healthy women (25 to 40 years) and from a fresh term placenta (n= 1), respectively. Stem cells were characterized and compared by flow cytometry using CD29, CD31, CD34, CD44, CD45, CD105, CD166 and HLA-DR markers. Osteocytes and adipocytes were differentiated from isolated human mesenchymal stem cells (HMSC). RESULTS: Adipose and placenta-derived MSC exhibited the same morphological features. ADSC differentiated faster than placenta; however, both were differentiated, taking up to 21 days for osteocyte and 14 days for adipocyte differentiation. About 90% of PLC-MSC and ADSC were positive for CD29, CD44, CD105, and CD166; and negative for CD31, CD34, CD45, and HLA-DR. CONCLUSION: The two sources of stem cells showed similar surface markers, morphology and differentiation potential and because of their multipotency for differentiating to adipocytes and osteocytes, they can be applied as attractive sources of MSC for regenerative medicine.

Pro-oxidant- Antioxidant Balance (PAB) in Rheumatoid Arthritis and its Relationship to Disease Activity.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that tends to be progressive and chronic. Previous studies showed that oxidative stress has a main role in pathology of RA. The aim of this study was the easy elucidation of oxidative stress through pro-oxidant-antioxidant balance (PAB) in these patients. METHOD: The sera of 130 RA patients and 130 age-matched healthy subjects (HS) were collected and the PAB was measured. According to the normal value of PAB in HS, the patients were divided into two groups; patients with increased serum PAB and those with normal serum PAB values. In patients with increased PAB value, the correlation of PAB value with RA disease activity [(DAS28ESR)], biochemical parameters, and BMI were determined. RESULTS: Significantly higher serum PAB values were found in the whole RA group of patients (88.69±39.42 HK) in comparison to HS (53.57±25.10 HK), p . 0.05. There was no significant correlation between PAB values and RA disease activity. In patients with elevated serum PAB value; serum cholesterol, triglycerides and BMI were significantly higher in comparison to patients with normal values. CONCLUSION: The PAB test can show the oxidative stress in RA patients. Further research should be done to determine the potency of the PAB assay as a tool for monitoring adverse effect of oxidative stress in RA, as well as the effect of antioxidant therapies in the outcomes.

Treatment of life-threatening wounds with a combination of allogenic platelet-rich plasma, fibrin glue and collagen matrix, and a literature review.

Currently there is no ideal procedure for the treatment of recalcitrant ulcers that are unresponsive to the majority of common treatments. However, several novel approaches have been proposed, including bone marrow stem cells, platelets, fibrin glue and collagen matrix. For the first approach treatment of a chronic wound, a non-invasive method is highly desirable. The present study was undertaken with the aim of evaluating the effect of a combination of platelets, fibrin glue and collagen matrix (PFC) in one treatment. A total of ten patients with aggressive, refractory, life-threatening wounds were recruited for the study and their treatment effects were evaluated. Initially, the ulcers were extensively debrided, measured and photographed at weekly intervals. The PFC combination was applied topically to the wound every two days. Following treatment, the wound was completely closed in nine patients and was markedly reduced in the other patient. The mean 100% healing time for the nine patients was 11.3±5.22 weeks. There was no evidence of local or systemic complications or any abnormal tissue formation, keloid or hypertrophic scarring. Therefore, the results of the present study indicate that in the first approach, the combination of PFC components may be used safely in order to synergize the effect of chronic wound healing.

Oxidative and antioxidative pathways might contribute to thromboangiitis obliterans pathophysiology.

Higher oxidative and lower antioxidative markers have been reported in patients with thromboangiitis obliterans (TAO) when compared with healthy control groups. However, the recent literature has not compared the results with healthy smokers, despite the observed effects of cigarette smoke on oxidative and antioxidative pathways. The aim of this study was to determine the oxidative stress status in TAO patients compared with healthy smokers, through direct assessment of the pro-oxidant-antioxidant balance (PAB) assay. The study included 21 patients with TAO, 19 smokers and 17 non-smokers. Comparison between groups revealed a significant increase in PAB value in the TAO group when compared with the smoker (P= 0.001) and non-smoker (P< 0.001) groups. About 95% of TAO cases had PAB value more than 50 units. The PAB value more than 50 might increase the relative risk of TAO presentation about seven folds (relative risk [RR]= 7.464, confidence interval [Cl]= 95%). The increased PAB value in the TAO might be due to impairment of the oxidative and antioxidative pathways. Based on this hypothesis, the effect of cigarette smoke on oxidative stress might be exaggerated in TAO and may lead to inflammatory and thrombotic events. Further studies for evaluating antioxidant therapies on the outcome of TAO are recommended.

Successful treatment of congenital chyloperitoneum with platelet-rich fibrin glue.

BACKGROUND: Congenital chyloperitoneum is an uncommon clinical condition. A few cases of congenital chyloperitoneum in children have been described who were treated in a variety of methods. CASE PRESENTATION: Congenital chyloperito was diagnosed in a 5-day-old baby boy with a significant abdominal distension. Due to the failed conservative managements by medium-chain triglycerides (MCT) enriched milk and partial parenteral nutrition (PPN), the authors tried platelet rich fibrin glue (PRFG) as an alternative choice which was applied through an already inserted intra-abdominal catheter. PRFG successfully stopped the lymph leakage from all over the small intestinal mesentery; thereby PRFG may be considered as an effective alternative treatment before surgical intervention. CONCLUSION: Applying PRFG is an easy, safe, and effective alternative option that may be used to close the chylous ascites lymph leakage in children if conservative management with PPN fails.