MMC Group Research Articles

Interactions between myoblasts and macrophages under high glucose milieus result in inflammatory response and impaired insulin sensitivity.

Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance (IR). Many studies have confirmed the interactions between macrophages and skeletal muscle regulated the inflammation and regeneration of skeletal muscle. However, despite of the decades of research, whether macrophages infiltration and polarization in skeletal muscle under high glucose (HG) milieus results in the development of IR is yet to be elucidated. C2C12 myoblasts are well-established and excellent model to study myogenic regulation and its responses to stimulation. Further exploration of macrophages' role in myoblasts IR and the dynamics of their infiltration and polarization is warranted. To evaluate interactions between myoblasts and macrophages under HG, and its effects on inflammation and IR in skeletal muscle. We detected the polarization status of macrophages infiltrated to skeletal muscles of IR mice by hematoxylin and eosin and immunohistochemical staining. Then, we developed an in vitro co-culture system to study the interactions between myoblasts and macrophages under HG milieus. The effects of myoblasts on macrophages were explored through morphological observation, CCK-8 assay, Flow Cytometry, and enzyme-linked immunosorbent assay. The mediation of macrophages to myogenesis and insulin sensitivity were detected by morphological observation, CCK-8 assay, Immunofluorescence, and 2-NBDG assay. The F4/80 and co-localization of F4/80 and CD86 increased, and the myofiber size decreased in IR group (P < 0.01, g = 6.26). Compared to Mc group, F4/80+CD86+CD206- cells, tumor necrosis factor-α (TNFα), inerleukin-1β (IL-1β) and IL-6 decreased, and IL-10 increased in McM group (P < 0.01, g > 0.8). In McM + HG group, F4/80+CD86+CD206- cells, monocyte chemoattractant protein 1, TNFα, IL-1β and IL-6 were increased, and F4/80+CD206+CD86- cells and IL-10 were decreased compared with Mc + HG group and McM group (P < 0.01, g > 0.8). Compered to M group, myotube area, myotube number and E-MHC were increased in MMc group (P < 0.01, g > 0.8). In MMc + HG group, myotube area, myotube number, E-MHC, GLUT4 and glucose uptake were decreased compared with M + HG group and MMc group (P < 0.01, g > 0.8). Interactions between myoblasts and macrophages under HG milieus results in inflammation and IR, which support that the macrophage may serve as a promising therapeutic target for skeletal muscle atrophy and IR.

Role of Adjuvant Mitomycin C in The Endoscopic Treatment of Laryngotracheal Stenosis (Meta-Analytic Study)

Abstract Background Laryngotracheal stenosis is a life-threatening restriction in pulmonary ventilation. It is an umbrella term, including luminal compromise at the level of the larynx, subglottis, or trachea. Etiology of laryngotracheal stenosis is multifactorial. In adults and adolescents it is mostly acquired, where in children it may be acquired or congenital. Acquired laryngotracheal stenosis can result from previous intubation or tracheostomy, systemic disease, trauma, infection, or idiopathic causes. Historically, infectious etiology was common. Currently, laryngotracheal stenosis most frequently results from prolonged intubation or trauma from intubation itself. Objective To evaluate the effectiveness of topical Mitomycin C as an adjuvant treatment with the endoscopic management of laryngotreacheal stenosis. Patients and Methods The total number of patients in all the included studies was 454, 379 patients in MMC group and 75 patients in non-MMC group. Results This meta-analysis study showed that resolution (success) rate in MMC group was (68.7%) and there was a significant increase in resolution (success) rate in MMC compared to non- MMC group (p = 0.011) with the odds of being 5 times higher in MMC group (OR = 5.04). The Complications rate in MMC using patients was (4%). The result of this meta-analysis study showed that Mitomycin C is an effective and safe adjuvant in the endoscopic treatment of laryngotracheal stenosis. However, this study included limitations. We recommend the need of more high quality prospective randomized controlled trials, two armed studies and further studies in the future to achieve stronger results. Conclusion We suggest that that Mitomycin C is an effective and safe adjuvant in the endoscopic treatment of laryngotracheal stenosis. However, this study included limitations. We recommend the need of more high quality prospective randomized controlled trials, two armed studies and further studies in the future to achieve stronger results.

A comparative study between amniotic membrane transplantation and topical mitomycin-C in recurrent pterygium management

Aim The aim of this study was to compare the outcome of amniotic membrane transplantation (AMT) and topical mitomycin-C (MMC) in the management of recurrent pterygia. Patients and methods This is a retrospective study that included 40 cases of recurrent pterygia. They were subjected to surgical excision of the pterygium with bare sclera technique. The cases were categorized into two groups, 20 cases in each group. Group 1 was managed with intraoperative topical MMC, while group 2 was managed with AMT at the time of surgery. The patients were followed-up for at least 6 months postoperatively. The outcome measures were visual acuity (VA), corneal astigmatism, recurrence, and postoperative complications. Results The duration of postoperative pain was significantly shorter in the AMT group (6.8±1.0 days) than in the MMC group (10.45±1.5 days, P&lt;0.0001). In addition, postoperative photophobia and lacrimation persisted for a significantly longer period in the MMC group (mean=10.0±1.03 days) compared to the AMT group (mean=7.85±0.81 days, P&lt;0.0001). At the end of follow-up period, VA improvement occurred in 60% of group 1 and in 70% of group 2 patients. However, the preoperative and postoperative decimal VA were not significantly different between the two study groups (P=0.6684 and 0.7302, respectively). In group 1, there was a significant difference between the preoperative corneal astigmatism [−3.74±2.19 diopter (D)] and the postoperative astigmatism (−2.31±1.46 D) after 6 months (P&lt;0.01). Similarly, in group 2, there was also a significant difference between the preoperative corneal astigmatism (−3.83±2.32 D) and the postoperative astigmatism (−2.12±1.60 D) after 6 months (P&lt;0.01). However, the difference between the two groups was statistically insignificant. In the first postoperative 2 weeks, there was a statistically insignificant higher incidence of delayed wound healing and superficial punctate keratitis in the MMC group. The corneal wound healing was faster in the AMT group (mean=4.2±0.69 days) than in the MMC group (mean=4.6±o.6 days). However, the difference was not statistically significant (P=0.0578). At 2 weeks postoperatively, there were two cases of conjunctival defect and one case of scleral thinning in the MMC group only. At the end of the follow-up period, another case, in the MMC group, developed scleral thinning; however, the cornea was clear. Conclusion AMT and MMC could be used in the management of recurrent pterygia. The AMT group showed better visual outcome without postoperative complications. However, the difference between the two groups was statistically insignificant.

INTRAOPERATIVE MITOMYCIN-C, 5-FLUOROURACIL, RETROBULBAR TRIAMCINOLON ACETONIDE, IS IT EQUALLY EFFECTIVE TO DECREASE INTRAOCULAR PRESSURE AFTER TRABECULECTOMY?

Objectives: To evaluate the effect of mitomycin-C (MMC), 5-fluorouracil (5-FU), and retrobulbar triamcinolone acetonide (TA) on the surgical result of trabeculectomy Materials and Methods: All consecutive trabeculectomies with releasable sutures performed in Sardjito General Hospital between January 2022 and December 2022 were retrospectively reviewed from medical records. Patients without any intraoperative metabolite (control group, n=5) were compared to those with retrobulbar TA (n=5), MMC group (n=19), and 5-FU group (n=11) in terms of surgical success. Successful surgery results were defined as IOP between 5 - 21 mm Hg without any further medications or surgical intervention and fewer complications. Results: 40 eyes of 35 patients (15 male, 25 female, mean age 52.4 years) were included in the study. The IOP pre operative in TCA group was 47.12 ±12.16 mmHg, in MMC group was 35.53 ± 17.05 mmHg, in 5-FU group was 34.54 ± 17.77 mmHg, and 43.80 ± 15.79 mmHg in group without any metabolite. The patient was observed until the post-operation day (POD) 90. There were no significant differences in intraocular pressure at POD 1, 7, 30, 60, and 90 between the control group compared to TCA, MMC, and 5-FU group. In TCA group, pre operative IOP was 47.12 ±12.16 mmHg then decreases to 15.60 ± 4.61 mmHg at POD 90. In MMC group, pre operative IOP was 35.53 ± 17.05 mmHg, 90 days later became 14.42 ± 5.71 mmHg. In 5-FU group, pre operative IOP was 34.54 ± 17.77 mmHg then decrease to 13.64 ± 4.08 mmHg. In group without metabolite, pre operative IOP was 43.80 ± 15.79 mmHg, then became 21.00 ± 6.81 mmHg at POD 90. The lowest mean intraocular pressure of POD 90 was in the 5-FU group (13.64 ± 4.08 mmHg). Complication after trabeculectomy in the TCA group was 21%, the MMC group was 27%, the 5-FU group was 10%, and the control group was 42%. Conclusion: MMC, 5-FU, and TCA in this study are equally effective to decrease IOP after trabeculectomy.

INTRAOPERATIVE MITOMYCIN-C, 5-FLUOROURACIL, RETROBULBAR TRIAMCINOLON ACETONIDE, IS IT EQUALLY EFFECTIVE TO DECREASE INTRA OCULAR PRESSURE AFTER TRABECULECTOMY?

Introduction &amp; ObjectivesTo evaluate the effect of mitomycin-C (MMC), 5-fluorouracil (5-FU), and retrobulbar triamcinoloneacetonide (TA) on the surgical result of trabeculectomy.&#x0D; MethodsAll consecutive trabeculectomies with releasable sutures performed in Sardjito General Hospitalbetween January 2022 and December 2022 were retrospectively reviewed from medical records.Patients without any intraoperative metabolite (control group, n=5) were compared to those withretrobulbar TA (n=5), MMC group (n=19), and 5-FU group (n=11) in terms of surgical success.Successful surgery results were defined as IOP between 5 - 21 mm Hg without any furthermedications or surgical intervention and fewer complications.&#x0D; Results40 eyes of 35 patients (15 male, 25 female, mean age 52.4 years) were included in the study. Patientwas observed until post-operation day (POD) 90. There were no significant differences of intraocularpressure at POD 1, 7, 30, 60, and 90 between control group compared to TCA, MMC, and 5-FUgroup. Intraocular pressure pre- and post-operation in each group was significantly different(p&lt;0.05). The lowest mean intraocular pressure of POD 90 was in 5-FU group (13.64 ± 4.08).Complication after trabeculectomy in TCA group was 21%, MMC group was 27%, 5-FU group was10%, and control group was 42%.&#x0D; ConclusionMMC, 5-FU, and TCA in this study are equally effective to decrease IOP after trabeculectomy.

Trabeculectomy with concurrent intravitreal bevacizumab in neovascular glaucoma.

To evaluate the clinical efficacy of concurrent intravitreal bevacizumab (IVB) injection with trabeculectomy with mitomycin-C (MMC) in neovascular glaucoma (NVG). Patients with NVG who underwent trabeculectomy with concurrent IVB (group 1) and those who underwent IVB sequentially, followed by trabeculectomy with MMC (group 2) in 1-2 weeks between January 2021 and August 2022, were included in this retrospective hospital-based study. The need for medications for intraocular pressure (IOP) control at 6 months in the two groups was the primary outcome measured and compared between the groups. The association of the need for medications postoperatively with clinical variables was assessed using stepwise multivariate regression statistics. We finally included 40 patients ( n = 12 in group 1, n = 28 in group 2) with no significant differences in presenting age between groups. The IOP at 1 day and 1 week were not significantly different between groups though the IOP at 1, 3, and 6 months. IOP was lower in group 1 eyes with the 6-month IOP, being significantly lower in group 1, P = 0.05. Three eyes in group 1 and 11 eyes in group 2 required anti-glaucoma medications in the postoperative period. Multivariate regression identified preoperative IVB >3 (β =0.7, P < 0.001) and recurrent vitreous hemorrhage (β = 0.7, P = 0.004) as prognostic factors ( R2 = 40.6%) determining the need for anti-glaucoma medication (AGM) postoperatively in both groups. Concurrent IVB with trabeculectomy with mitomycin-C is a feasible alternative in patients with NVG with refractory high-presenting IOP. This may serve to address raised IOP as well as retinal ischemia, thereby improving surgical success rates in the most challenging NVG cases.

Age-Specific Probability of 4 Major Health Outcomes in Children with Spina Bifida.

This study aimed to estimate the age-specific probability of 4 health outcomes in a large registry of individuals with spina bifida (SB). The association between age and 4 health outcomes was examined in individuals with myelomeningocele (MMC, n = 5627) and non-myelomeningocele (NMMC, n = 1442) from the National Spina Bifida Patient Registry. Sixteen age categories were created, 1 for each year between the ages of 5 and 19 years and 1 for those aged 20 years or older. Generalized linear models were used to calculate the adjusted probability and 95% prediction intervals of each outcome for each age category, adjusting for sex and race/ethnicity. For the MMC and NMMC groups, the adjusted coefficients for the correlation between age and the probability of each outcome were -0.933 and -0.657 for bladder incontinence, -0.922 and -0.773 for bowel incontinence, 0.942 and 0.382 for skin breakdown, and 0.809 and 0.619 for lack of ambulation, respectively. In individuals with SB, age is inversely associated with the probability of bladder and bowel incontinence and directly associated with the probability of skin breakdown and lack of ambulation. The estimated age-specific probabilities of each outcome can help SB clinicians estimate the expected proportion of patients with the outcome at specific ages and explain the probability of the occurrence of these outcomes to patients and their families.

Single-Dose Post-Office Fulguration Mitomycin C Instillation Appears to Improve Recurrence-Free Survival in Patients With Low-Grade Noninvasive Bladder Cancer.

Perioperative instillation of mitomycin-C (MMC) has shown effectiveness in reducing the recurrence of low-grade non-muscle invasive bladder cancer (NMIBC). Data is lacking about the impact of single-dose MMC following office fulguration of low-grade urothelial carcinoma. We compared the outcomes of small-volume low-grade recurrent NMIBC in patients treated with office-fulguration - with and without an immediate single-dose instillation of MMC. A retrospective analysis of medical records of patients with recurrent small-volume (≤1 cm) low-grade papillary urothelial cancer who underwent fulguration in a single institution between January 2017 and April 2021 either with or without instillation of post-fulguration MMC (40mg/50 mL). The primary outcome was recurrence-free survival (RFS). Of 108 patients (27% women) who underwent fulguration, 41% received intravesical MMC. The treatment and control groups had similar sex ratio, mean age, mass size, tumor multifocality and or tumor grade. Median RFS was 20 months (95% CI 4-36) in the MMC group and 9 months (95% CI 5-13) in the control group (P=.038). Multivariate Cox regression analysis showed that MMC instillation was associated with longer RFS (OR=0.552, 95% CI 0.320-0.955, P=.034) and multifocality was associated with shorter RFS (OR=1.866, 1.078-3.229, P=.026). A higher rate of grade 1-2 adverse events was observed in the MMC group (18.2%) vs. the control (6.8%, P=.048). No complications grade 3 or higher were observed. A single dose of MMC instilled after office fulguration is associated with longer RFS compared to patients who did not receive MMC after the procedure, with no associated high-grade complications.

Folic acid supplementation rescues bladder injury in fetal rats with myelomeningocele.

Bladder dysfunction has been linked to the progression of renal failure in children with neurogenic bladder (NB) dysfunction. The purpose of this study was to determine whether bladder injuries in fetal rats with myelomeningocele (MMC) may be treated with folic acid. Pregnant Sprague-Dawley rats were randomly divided into three groups. On the 10th day of gestation, pregnant rats were intragastrically injected with all-trans retinoic acid (ATRA) (60 mg/kg) to induce MMC fetal rats. The same amount of olive oil was put into the control group to create normal fetal rats. The rats in the rescue group were given folic acid (40 mg/kg) by gavage 0.5 and 12 hr after ATRA therapy. Bladders were obtained via cesarean section on embryonic day E20.5 and examined for MMC. The histology of the fetuses was examined using hematoxylin and eosin staining, and immunohistochemistry (IHC) was utilized to determine the expression of α-smooth muscle actin (α-SMA) and neuron-specific nuclear-binding protein (NeuN). Furthermore, the levels of neuromuscular development-related and apoptotic proteins were determined by western blotting. The incidence of MMC in the model group was 60.6% (20/33) while it was much lower in the rescue group (21.4%). In comparison to the model group, the weight and crown-rump length of the fetal rats in the rescue group were significantly improved. IHC revealed that there was no significant difference in the expression of α-SMA and NeuN between the control and ATRA groups, while the expression levels decreased significantly in the MMC group. Western blot analysis showed that there was no significant difference between the model and ATRA groups, but the expression of the α-SMA protein and the β3-tubulin was much lower in the MMC group than in the control group. After the administration of folic acid, the α-SMA and β3-tubulin proteins considerably increased in the folic acid-rescued MMC group and folic acid-rescued ATRA group. Meanwhile, in the control group, the expression of cleaved caspase-3 in the bladder tissue was significantly higher, and the expression of poly (ADP-ribose) polymerase (PARP) protein was significantly lower compared to the control group. Folic acid therapy reduced cleaved caspase-3 expression while increasing PARP expression in comparison to the MMC group. NB in MMC fetal rats is associated with the reduction of bladder nerve and smooth muscle-related protein synthesis. However, folic acid therapy can help improve these functional deficiencies. Folic acid also exhibits strong anti-apoptotic properties against NB in MMC fetal rats.

Evaluation of Knee Position Sense in Children with Motor Disabilities and Children with Typical Development: A Cross-Sectional Study.

In children with motor disabilities, knee position during walking is often of concern in rehabilitation. This study aimed to investigate knee joint position sense. Thirty-seven children with Cerebral Palsy (CP), 21 with Myelomeningocele (MMC), 19 with Arthrogryposis (AMC), and 42 TD children participated in the study. Knee joint position sense, i.e., the difference between the criterion angle and the reproduced angle (JPS-error), was assessed in sitting while 3D motion capture was recorded at flexed knee 70 (Knee70), 45 (Knee45), and 20 (Knee20) degrees, and after three seconds at maintained criterion angle (CAM) and maintained reproduced angle (RAM). No differences were found between the groups in JPS-error, CAM, and RAM. At Knee70, CAM differed between the right and left legs in the TD group (p = 0.014) and RAM in the MMC group (p = 0.021). In the CP group, CAM was greater than RAM at Knee70 in the left leg (p = 0.002), at Knee45 in both legs (p = 0.004, p = 0.025), and at Knee20 in the right leg (p = 0.038). Difficulties in maintaining the knee position at CAM in the CP group sheds light on the need for complementary judgments of limb proprioception in space to explore the potential influence on knee position during walking.

The anti-scar effect of tyrosine-kinase inhibitor nintedanib in experimental glaucoma filtration surgery in rabbits

PurposeTo investigate the efficacy of nintedanib on preventing postoperative scar in formation following glaucoma filtering surgery (GFC) in rabbits in comparison with Mitomycin-C (MMC). DesignExperimental Animal Study. Methods24 New Zealand rabbits were divided randomly into 3 groups as Sham, Nindetanib and MMC(n = 8). Limbal-based trabeculectomy was performed on the right eyes of the rabbits. Left eyes that did'nt undergo surgery were included in the control group (n = 8). Following surgery, Intraocular pressures (IOP), postoperative complications and morphological changes in the bleb were evaluated. On the 28th day, eight eyes from each group were enucleated and histologically and immunohistochemically analyzed. Matrix metalloproteinase-2 (MMP-2), Transforming Growth Factor-1 (TGF-B1) and alpha-smooth muscle actin (a-SMA) were evaluated. ResultsIt was observed that nintedanib has no side effects and reduces subconjunctival fibrosis. Postoperative IOP values in the Nindetanib group were lower than the other groups (p < 0.05). The longest bleb survival was observed in the Nintedanib group and the shortest in the Sham group (p < 0.001). Conjunctival vascularity and inflammation was reduced in the Nintedanib group compared to the Sham group (p < 0.05). The highest subconjunctival fibrosis was observed in the Sham group and the least in the Nintedanib group (p < 0.05). Although the fibrosis score was found lower in the Nintedanib group compared to the MMC(p > 0.05). α-SMA TGF-β1, MMP-2 expressions were similar in Nintedanib and MMC groups (p > 0.05), however, it was observed that significantly decreased in both groups compared to Sham group (p < 0.05). ConclusionIt has been observed that Nindetanib suppress fibroblast proliferation Thus, It may be a drug that can prevent subconjunctival fibrosis in GFC.

Quality of life in patients with non-muscle invasive bladder tumor undergoing adjuvant intravesical treatment

IntroductionThe objective of the study was to establish a possible relationship between mitomycin-C (MMC) and bacillus Calmette-Guérin (BCG) treatments and quality of life impairment. Material and MethodsQuasi-experimental, prospective, and longitudinal study including patients undergoing adjuvant treatment in NMIBC. The Short form-12 (SF-12) and Urogenital Distress Inventory-6 (UDI-6) questionnaires were used to measure quality of life. Questionnaire scores were compared between cases with MMC and BCG before induction (M1), at 4 weeks (M2) and at 2 months (M3). ResultsOf the 90 patients enrolled, 54 were in the BCG group and 36 in the MMC group. It was found that BCG patients had worse perceived physical quality of life compared to MMC patients in M2 (OR:2.59, p=0.046). In addition, significant changes were found in the urinary quality of life of patients on MMC treatment between the different time points (UDI-6 score: 33.33 in M1, 27.78 in M2 and 16.67 in M3, p=0.001). ConclusionsThere are no differences in urinary quality of life between patients treated with MMC and BCG. Patients with MMC show a significant recovery of urinary quality of life from the completion of the induction course, which becomes even more significant after 2 months. In addition, BCG-treated patients have worse physical quality of life after 4 weeks of treatment than those treated with MMC.

Calidad de vida en pacientes con tumor vesical no músculo-invasivo sometidos a tratamiento adyuvante intravesical

IntroductionThe objective of the study was to establish a possible relationship between mitomycin-C (MMC) and bacillus Calmette-Guérin (BCG) treatments and quality of life impairment. Material and methodsQuasi-experimental, prospective, and longitudinal study including patients undergoing adjuvant treatment in NMIBC. The Short form-12 (SF-12) and Urogenital Distress Inventory-6 (UDI-6) questionnaires were used to measure quality of life. Questionnaire scores were compared between cases with MMC and BCG before induction (M1), at 4 weeks (M2) and at 2 months (M3). ResultsOf the 90 patients enrolled, 54 were in the BCG group and 36 in the MMC group. It was found that BCG patients had worse perceived physical quality of life compared to MMC patients in M2 (OR:2.59, p=0.046). In addition, significant changes were found in the urinary quality of life of patients on MMC treatment between the different time points (UDI-6 score: 33.33 in M1, 27.78 in M2 and 16.67 in M3, p=0.001). ConclusionsThere are no differences in urinary quality of life between patients treated with MMC and BCG. Patients with MMC show a significant recovery of urinary quality of life from the completion of the induction course, which becomes even more significant after 2 months. In addition, BCG-treated patients have worse physical quality of life after 4 weeks of treatment than those treated with MMC.

Systemic Interleukin-6 Response after Intravesical Instillation of Bacillus Calmette-Guérin and Mitomycin C in Superficial Bladder Cancer.

Interleukin-6 (IL-6) is proposed to play a significant role in pathogenesis of urinary bladder cancer (UBC). This role may be influenced by chemotherapy (mitomycin C; MMC) or immunotherapy (Bacillus Calmette-Guérin; BCG). A case-control study was conducted to determine IL-6 levels in serum of newly diagnosed cases (NDC) of superficial UBC, as well as in patients treated with MMC or BCG intravesical instillation. A total sample of 111 patients (36 NDC, 45 MMC and 30 BCG) was included, as well as a control group of 107 healthy controls (HC). IL-6 was detected by enzyme-linked immunosorbent assay. Results revealed that median levels of IL-6 were significantly elevated in NDC group (15.8 pg/mL; P<0.001) compared to MMC and BCG groups (7.5 and 5.3 pg/mL, respectively) or HC (4.4 pg/mL); while, there were no significant differences between the latter three groups (MMC, BCG and HC). Receiver operating characteristic curve analysis revealed that IL-6 is a very good predictor of UBC in NDC group versus HC (area under the curve=0.885; 95% confidence interval=0.828-0.942; P<0.001; cut-off value=10.5 pg/mL; Youden index=0.62; sensitivity=80.6%; specificity=81.3%). Logistic regression analysis confirmed this significance and IL-6 was associated with a higher risk of UBC (odds ratio=1.18; 95% confidence interval=1.11-1.26; P<0.001). In conclusion, this study indicated that IL-6 level was upregulated in serum of NDC of UBC. Further, IL-6 level was restored to normal levels after intravesical instillation of MMC or BCG.

Differences between myelomeningocele and myeloschisis lesions in patients undergoing open in-utero spina bifida repair

Spina bifida lesions are broadly classified as myelomeningocele (MMC: with sac) and myeloschisis (MSC: without sac) lesions, with MSC being the most severe type. Although prenatal repair methods are similar, baseline differences, surgical management, and postnatal outcomes remains largely unknown. The objective was to compare prenatal findings, closure methods, and 12-month outcomes. A prospective cohort of 111 open in-utero repair consecutive patients at a single institution were assessed (2011-2022). Lesion type was defined by ultrasound for the presence of a sac elevated from the lesion. Surgical eligibility was similar to the MOMS study, but expanded BMI inclusion criteria to ≤40 from 2018. Intraoperative management was pediatric neurosurgeon dependent. We compared preoperative differences in ventricular sizes, tonsillar herniation levels, extremity function, skin patch requirement, and neonatal outcomes including cerebrospinal fluid (CSF) leakage, wound dehiscence, and CSF diversion procedures until 12 months of age. Significance was considered at a p=0.05. Ultrasound and MRI identified 60 cases that were MMC and 51 as MSC. Maternal demographics, the gestational age (GA) at prenatal evaluation and the upper level of lesion were similar between groups (Table 1). Preoperative ventricular measurements were greater in the MMC cases. There were no differences in the upper level of lesions. MSC has severe baseline tonsillar herniation compared to MMC. There was higher talipes and loss of baseline motor function in the MMC group. The need for a skin closure patch was 21.7% in MMC vs 43.1% in MSC (p=0.002; Table 2). The length of NICU stay was 17 days longer in the MSC vs. the MMC group. There were no differences in ventricular diversion rates within a year from birth. Prenatally diagnosed MMC is associated with greater ventriculomegaly and talipes, and with less tonsillar herniation and fetal movement than those with MSC defects. Longer NICU stays in the MSC group is secondary to the higher need for skin closure with a patch and delayed healing.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The Inhibitory Effect of Connective Tissue Growth Factor Antibody on Postoperative Fibrosis in a Rabbit Model of Trabeculectomy.

To compare the efficacy of subconjunctival injection of an anti-connective tissue growth factor antibody (anti-CTGF) versus mitomycin-C (MMC) and placebo in reducing scar formation in a rabbit model of trabeculectomy. A total of 14 rabbits were included. Nine rabbits underwent trabeculectomy with subconjunctival injections of either anti-CTGF antibody, MMC, or balanced salt solution (BSS), each administered in three eyes, before peritomy. The anti-CTGF group received a repeated dose of the antibody five days after surgery. All nine rabbits were euthanized on day 14; the globes were stained with hematoxylin & eosin, Masson's Trichrome, and immunohistochemistry for detecting alpha-smooth muscle (α-SMA) actin. RNA extraction was performed on five eyes of the remaining rabbits which included one eye without any surgery, one eye 5 hr after trabeculectomy without any injection, one eye five days after trabeculectomy without any injection, and two eyes five days after trabeculectomy with administration of MMC and BSS, respectively. The mean bleb area in the anti-CTGF, MMC, and control groups was 3.8 1.45, 5.9 1.4, and 3.5 1.9 mm2, respectively. Collagenous tissue was found to occupy the bleb area by 13.7%, 13.5%, and 18.5%, respectively. This ratio was significantly higher in the BSS group (P = 0.04). The expression of CTGF mRNA after 5 hr and five days in eyes undergoing trabeculectomy were significantly more pronounced as compared to the unoperated eye. The mean H-SCORE of α-SMA-immune reactive cells calculated as the grade of staining multiplied by the percentage of immune stained cells was 14.6, 10.22, and 140.58 in the anti-CTGF, MMC, and control groups, respectively. While the control eyes had a significantly higher score (Ps 0.001), the anti-CTGF and MMC groups were comparable (P = 0.87). Based on the results of this animal study, the anti-CTGF antibody injection resulted in a significant reduction in collagenous tissue and myofibroblast cells after trabeculectomy.

The effect of fibrin glue on suppressing Transforming Growth Factor-β (TGF-β) expression compared to Mitomycin-C (MMC) and Triamcinolone Acetonide (TCA) as antifibrotic agents in contracted socket prevention

Background: Post-evisceration fibrosis remains the leading cause of contracted socket. The application of fibrin glue is considered an alternative adjuvant therapy in suppressing profibrotic factor (TGF-β) expression following evisceration surgery to prevent contracted socket. This study aimed to know the role of fibrin glue in suppressing the TGF-β expression following evisceration surgery. Methods: An in vivo experimental study with a randomized post-test-only control group using twenty New Zealand rabbits were conducted. The sample was divided into four groups, each consisting of five rabbits, and one healthy eye was selected randomly for evisceration. Each rabbit in the study group was given a subconjunctival injection of agents corresponding to each study group, namely: Group I (control [no injection]), Group II (0.1 ml MMC 0.4 mg/ml), Group III (0.1 ml TCA 40 mg/ml), and Group 4 (0.1 ml fibrin glue) at the inferior fornix. Following a 14-day observation period, the animals were euthanized, and tenon conjunctiva in inferior fornix samples was collected for immunohistochemistry (IHC) staining examination. The pathologist calculates the immunoreactive scores (IRS) for each specimen. The differences in TGF-β expression were statistically analyzed with a significant p&lt;0.05. Data were analyzed using SPSS version 26 for Windows. Result: The highest TGF-β expression was found in the control group (I), and the lowest was in the mitomycin-C group (III), followed by the triamcinolone group (IV) and fibrin glue group (II). There were significant differences in TGF-β expression among the four groups (p=0.004). The difference between fibrin glue, MMC, and triamcinolone acetonide groups was insignificant (p&gt;0.05). Conclusion: As an alternative to mitomycin-C and triamcinolone acetonide, fibrin glue can be used as adjuvant therapy to prevent constricted sockets after evisceration.

Fibrin glue as a novel therapy for contracted socket in comparison to mitomycin-c and triamcinolone acetonide at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia

Background: Contracted socket is still a major problem for patients with anophthalmia. The main factor for this condition is inflammation and fibrosis, which result in conjunctival shortening. Myofibroblasts that express α-SMA are the primary mediators of anophthalmic socket contraction. Methods: One healthy eye of a New Zealand white rabbit were randomly selected for evisceration and divided into four treatment groups, each with five rabbits. Each rabbit in the group received a single subconjunctival injection of a different agent. Group, I was the control group that received no injection, Group II received MMC 0.4 mg/ml, Group III received TCA 40 mg/ml, and Group 4 received fibrin glue. After 14 days, the animals were euthanized, and conjunctival samples were submitted for histopathological analysis. A monoclonal α-SMA antibody was applied, and pathologists provided the IRS score for each sample. The differences in α-SMA expression were statistically analyzed with a significant level of p &lt;0.05 Result: All groups displayed a statistically significant decrease in α-SMA expression compared to the control group (p&lt;0.05) as sorting as MMC group with p=0.007, TCA group with p=0.007, and fibrin glue with p= 0.009. MMC was the most effective at reducing α-SMA (p=0.004). Surprisingly, there were no statistically significant differences between MMC, TCA, and fibrin glue when they were evaluated independently. Conclusion: A single subconjunctival injection of fibrin glue may be used as a novel treatment to prevent socket contracture in actively healing sockets.

The effect of Mitomycin-C in neoadjuvant concurrent chemoradiotherapy for rectal cancer.

Neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by total mesorectal excision has become the standard of care for advanced rectal cancer, but the most effective regimen of chemotherapeutic agents has not yet been determined. The purpose of this study is to determine the effect of Mitomycin-C (MMC) in nCCRT for rectal cancer. From 2000 to 2017, patients with rectal adenocarcinoma who received nCCRT followed by radical surgery were enrolled in our study. The patients were retrospectively separated into two groups according to nCCRT regimens (with or without MMC). Other factors related to cancer down-staging after nCCRT, disease-free survival (DFS) and overall survival (OS) were analyzed. One hundred ninety-five patients received radiotherapy (RT) + MMC + oral tegafur-uracil (UFUR), and 191 patients received RT + UFUR without MMC as neoadjuvant CCRT. Adding MMC might increase the down-staging rate (odds ratio [OR] = 1.520, p = 0.058), and down-staging had significant effect to improve OS (OR = 1.726, p = 0.002) and DFS (OR = 2.185, p < 0.001). The OS and DFS were improved in patients who received MMC, although this result did not reach a statistically significant difference. There was a higher incidence of low-grade toxicities in the MMC group, especially neutropenia, genitourinary side effects, and dermatological side effects ( p < 0.001). Adding MMC to the regimen of nCCRT for rectal adenocarcinoma is shown to increase tumor down-staging rate and improve disease-free and OS, although these benefits come at the cost of increased low-grade toxicities. Prospective randomized studies are needed to explore the role of MMC in nCCRT for rectal cancer.

Intrauterine neuromuscular and stromal dysplasia of the bladder in retinoic acid-induced myelomeningocele fetal rats

ObjectivesTo observe the changes in the bladder of fetal rats with myelomeningocele (MMC) induced by all-trans retinoic acid (atRA) during the embryonic development stages. MethodsThe fetal rat model of MMC was induced by intragastric administration of atRA to pregnant rats on embryonic day 10 (E10). Fetal rats were harvested at E16, E18, E20, and E21 for observation and further testing. Those with MMC were classified as the MMC group, while those without MMC as the RA group. The areas of MMC skin defect, the crown-rump length (CRL), and body weight in different groups were compared. The histopathological changes in the bladder were compared. The expression levels of alpha-smooth muscle actin (αSMA), smooth muscle myosin heavy chain (SMMHC), connexin 43 (Cx43), desmin, β3 tubulin, and vesicular acetylcholine transporter (VAChT) in the bladder were investigated by immunohistochemical staining and Western blotting. Pregnant rats given intragastric administration with olive oil (OIL group) at E10 were set as the blank control group. ResultsA total of 415 fetal rats of different gestational ages were harvested with an MMC incidence of 56.05 % (139/248). The incidence rate increased with embryonic days (p < 0.001). Compared with the other two control groups, the CRL and bodyweight of MMC fetal rats were significantly delayed at E21 (p < 0.001). The expression levels of αSMA, SMMHC, Cx43, desmin, β3 tubulin and VAChT in the bladder of MMC fetal rats were significantly decreased at E21 (p < 0.05). ConclusionsIn atRA-induced MMC fetal rats, there is neural, muscular, and stromal dysplasia in the bladder at an early gestational age. Further investigations on neurogenic bladder secondary to MMC are applicable using this animal model.