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We continue our review of on punctal stenosis by providing a detailed discussion of management modalities, their complications, and outcomes. There is a significant change in the understanding of punctal and peripunctal anatomy, puncto-canalicular junction, and the lacrimal pump mechanisms. While the snip punctoplasty procedures are still practiced, there is an increasing trend toward nonincisional procedures. The nonincisional procedures in select cases appear to be equally effective as the incisional ones. Although simple to use, punctal plugs never became the mainstay of treatment because of design issues and the inability to address the coexisting canalicular stenosis. Placing stents only in the lower punctum in cases of upper and lower punctal stenosis should be discouraged, and management needs to address punctal stenosis and not which punctum is involved. Several types of stents are used in the management of punctal stenosis, mostly based on surgeon's preference. The benefits of adjuvant mitomycin C are uncertain. In view of literature on how stent biofilms can themselves cause chronic inflammation, placing them for prolonged periods should be reviewed and debated. Enhanced understanding of the molecular pathogenesis of punctal stenosis and addressing the current controversies in management would help standardize the therapeutic interventions available in the lacrimal armamentarium. [ABSTRACT FROM AUTHOR]

• Hyperthermia-assisted chemotherapy offers a promising approach for NMIBC treatment. • COMBAT and BR-TRG-I show potential in reducing recurrence in NMIBC patients. • Unithermia's efficacy appears inferior to BCG in high-risk NMIBC. • Conduction hyperthermia devices present varied outcomes in NMIBC treatment. • Further research with standardized protocols is essential for conclusive results. Intravesical treatment for non-muscle invasive bladder cancer (NMIBC) aims to reduce recurrences and stop progression. Hyperthermia-enhanced chemotherapy with devices like COMBAT BRS, Unithermia, and BR-TRG-I is a promising alternative to conventional Bacillus de Calmette Guerin (BCG) therapy. To systematically review the efficacy of hyperthermia generated by conduction devices in the treatment of NMIBC. The review followed the preferred reporting items for systematic reviews and meta-analyses guidelines. A search was performed in the PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases. Two reviewers independently assessed the eligibility of candidate studies and abstracted data from studies that met the inclusion criteria. The primary endpoint was assessment of recurrence. Secondary objectives included evaluation of treatment progression and safety. Thirty studies meeting inclusion criteria underwent data extraction. In intermediate-risk NMIBC patients, COMBAT versus mitomycin C (MMC) in normothermia revealed no superiority in reducing recurrence or progression. High-risk NMIBC patients using COMBAT achieved similar or superior outcomes to BCG. BR-TRG-I demonstrated superior results over normothermia in intermediate- and high-risk NMIBC patients. Unithermia proved less effective than BCG in high-risk NMIBC. Progression outcomes were promising with COMBAT and BR-TRG-I, but comprehensive analysis was limited due to inconsistent assessment across studies. Adverse events were primarily mild-moderate, with some device-specific differences. Studies on conduction hyperthermia present great variability, which do not allow us to determine the superiority of 1 device over another in terms of recurrence, progression, and/or adverse effects. Further research with consistent administration protocols is crucial for definitive conclusions [ABSTRACT FROM AUTHOR]

Mitomycin C (MMC) has an antitumor effect and is considered as a broad‐spectrum antibiotic. Sijunzi Decoction (SJZD), a well‐known ancient Chinese prescription, is widely used in the treatment of cancer when combined with chemotherapy drugs. Studies have shown that SJZD can be combined with other drugs to enhance the therapeutic effect against cancer and inhibit the toxicity of chemotherapy drugs, but the specific mechanism is not clear. Thus, we hope to further explore the antitumor mechanism of combined SJZD and MMC. 3‐(4,5‐Dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2‐H‐tetrazolium bromide assay, flow cytometry, western blot, 1H NMR and HPLC–MS were used to study the mechanism at the cellular level. The results show that the combined administration can have a more significant effect on inhibiting the proliferation of cancer cells, promoting their apoptosis. Based on metabolomics, 38 biomarkers were found in the MMC group and 43 biomarkers were found in the combined administration group. Among them, 18 unique biomarkers were discovered in the combined administration group. Studies have shown that the antitumor mechanism of combined administration is related to amino acid metabolism, energy metabolism, lipid metabolism and nucleotide metabolism, among which amino acid metabolism is the most important. In addition, SJZD achieves the effect of toxin reduction and efficiency enhancement by improving the body's immunity and improving the oxidative stress environment. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy of a gelatin stent (XEN 45 Gel Stent; Allergan) implant in advanced glaucoma eyes that have failed prior aqueous shunt implantation. Methods: We retrospectively reviewed 6 patients with refractory glaucoma, defined as persistently high IOP (> 21 mmHg) despite taking at least 3 IOP-lowering medications subsequent to undergoing a glaucoma drainage device (GDD) with or without a second GDD or cilioablative procedure. Eyes with previous failed GDD underwent subconjunctival 0.3 cc (0.4 mg/ml) mitomycin C, tenonectomy, and placement of an ab- externo XEN stent. The outcome measures included change in IOP and the number of glaucoma medications. Success was defined as patients achieving an IOP ≤ 18 mmHg with a percentage reduction of 25% or 15 mmHg and 40% mean IOP reduction from baseline while taking the same number or fewer medications. Results: All six eyes with age of 77.6 ± 7.82 years who underwent XEN implantation following previous GDD surgery had primary open-angle glaucoma. The IOP decreased significantly from 32.33 ± 5.99 to 12.67 ± 3.27 mmHg (p < 0.001) with a follow-up of 13.9 ± 2 (11.7–16.7) months. Visual acuity and visual field remained stable after XEN placement. Compared to the baseline number of medications of 4.2 ± 0.8, all medication was discontinued except in one eye on two drops at the end of the follow-up. The overall surgical success rate was 100%. No complications, needling, or additional procedures were required. Conclusion: This study described successful implantation of the XEN stent following failed GDD. XEN Gel stent implantation associated with mitomycin C and tenonectomy can be considered a viable surgical option for patients with a history of previously failed tube shunt requiring further IOP lowering. [ABSTRACT FROM AUTHOR]

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Currently, there is a growing focus on aging and age-related diseases. The processes of aging are based on cell senescence, which results in changes in intercellular communications and pathological alterations in tissues. In the present study, we investigate the influence of senescent mesenchymal stem cells (MSCs) on endothelial cells (ECs). In order to induce senescence in MSCs, we employed a method of stress-induced senescence utilizing mitomycin C (MmC). Subsequent experiments involved the interaction of ECs with MSCs in a coculture or the treatment of ECs with the secretome of senescent MSCs. After 48 h, we assessed the EC state. Our findings revealed that direct interaction led to a decrease in EC proliferation and migratory activity of the coculture. Furthermore, there was an increase in the activity of the lysosomal compartment, as well as an upregulation of the genes P21, IL6, IL8, ITGA1, and ITGB1. Treatment of ECs with the "senescent" secretome resulted in less pronounced effects, although a decrease in proliferation and an increase in ICAM-1 expression were observed. The maintenance of high levels of typical "senescent" cytokines and growth factors after 48 h suggests that the addition of the "senescent" secretome may have a prolonged effect on the cells. It is noteworthy that in samples treated with the "senescent" secretome, the level of PDGF-AA was higher, which may explain some of the pro-regenerative effects of senescent cells. Therefore, the detected changes may underlie both the negative and positive effects of senescence. The findings provide insight into the effects of cell senescence in vitro, where many of the organism's regulatory mechanisms are absent. [ABSTRACT FROM AUTHOR]

Background While performing trabeculectomy in glaucomatous patients, application of mitomycin C or implanting ologen showed significantly improved long term outcomes. Objective: To compare the results of trabeculectomy with or without ologen implant and trabeculectomy with mitomycin C in glaucoma patients. Methods Ninety glaucomatous eyes were selected after matching for the operative suitability in each case and distributed into 3 groups. Group 1 underwent trabeculectomy, Group 2 had trabeculectomy with mitomycin C and Group 3 underwent trabeculectomy with ologen implant. Data was analyzed using one-way ANOVA and Kruskal-Wallis tests at 5% significance level. Results At 6 month postoperatively, significantly higher mean intraocular pressure (IOP) was found in Group 1 (p = .000). However, it did not vary significantly among Group2 and Group 3 (p = .25). In comparison to the other groups significantly higher mean bleb height was found in group 3 (p = .000). In Group 3 the incidence of anterior chamber reaction was significantly lower when compared to Group 1 (p = 0.021) and Group 2 (p = .024). In comparison to other two groups, thin cystic bleb was found to occur less significantly in Group 3 (p = .031). Significantly lower incidence of shallow anterior chamber was found in Group 3 in comparison to Group 2 (p = .024), though not in Group 1 (p = .34). Conclusion Considering safety and effectiveness, implantation of ologen in trabeculectomy could provide a promising alternative to the use of mitomycin C. [ABSTRACT FROM AUTHOR]

Introduction: To compare the efficacy and safety of trabeculectomy with a collagen matrix implant (Ologen®) versus trabeculectomy with mitomycin C (MMC) versus trabeculectomy with both Ologen® and MMC (OLO + MMC). Methods: This non-randomized study included 119 eyes of 101 patients with uncontrolled open-angle glaucoma who underwent trabeculectomy, either alone or combined with phacoemulsification. The data were initially recorded following a standard surgical protocol, using an electronic database with structured fields. The patients were divided into three groups: 44 received trabeculectomy with adjunctive MMC (MMC group), 34 received surgery with Ologen® (OLO group), and 41 received surgery with both Ologen® and MMC (OLO + MMC group). The main outcome measures were the change in intraocular pressure (IOP), change in number of medications needed, complete success rate (defined as IOP ≤ 20 mmHg and at least 20% IOP reduction without hypotensive medications), rate of complications, and rate of postoperative interventions. The follow-up period was 36 months. Results: IOPs significantly decreased (p = 0.01) in all groups across all study visits, decreasing from 19.8 ± 4.6 mmHg to 12.7 ± 4.2 mmHg in the MMC group, from 20.5 ± 4.7 mmHg to 13.9 ± 3.5 mmHg in the OLO group, and from 23.5 ± 6.1 mmHg to 13.1 ± 3.5 mmHg in the OLO + MMC group. After correcting for the baseline IOP, only the first two postoperative visits (first week and first month) showed a significantly greater IOP reduction in the OLO + MMC group. The number of hypotensive medications was significantly reduced from 3.1 ± 0.6 to 0.56 ± 1.1 in the MMC group, from 2.9 ± 0.4 to 0.83 ± 1.1 in the OLO group, and from 3.0 ± 0.6 to 0.45 ± 0.95 in OLO + MMC group, with no statistically significant differences among the groups (p = 0.57). The complete success rates were 63.6% in the MMC group, 67.6% in the OLO group, and 80.5% in the OLO +MMC group, with no statistically significant differences between the groups (p = 0.21). Suture release was significantly more frequent in the MMC group (86.1%) than in the OLO group (62.1%) and in the OLO + MMC group (45.9%; p = 0.02). Bleb needling, with (33.3%; p = 0.005) or without (66.7%; p = 0.0001) 5-fluorouracil injection (5-FU), was significantly more common in the MMC group. The highest complete success rate (61%) was observed in the OLO + MMC group. Conclusions: The use of Ologen® and mitomycin C provided similar surgical IOP reduction in glaucoma surgery compared with either MMC or Ologen® alone, but significantly reduced the need for postoperative interventions. [ABSTRACT FROM AUTHOR]

Background: Symbioses between primary producers and bacteria are crucial for nutrient exchange that fosters host growth and niche adaptation. Yet, how viruses that infect bacteria (phages) influence these bacteria-eukaryote interactions is still largely unknown. Here, we investigate the role of viruses on the genomic diversity and functional adaptations of bacteria associated with pelagic sargassum. This brown alga has dramatically increased its distribution range in the Atlantic in the past decade and is predicted to continue expanding, imposing severe impacts on coastal ecosystems, economies, and human health. Results: We reconstructed 73 bacterial and 3963 viral metagenome-assembled genomes (bMAGs and vMAGs, respectively) from coastal Sargassum natans VIII and surrounding seawater. S. natans VIII bMAGs were enriched in prophages compared to seawater (28% and 0.02%, respectively). Rhodobacterales and Synechococcus bMAGs, abundant members of the S. natans VIII microbiome, were shared between the algae and seawater but were associated with distinct phages in each environment. Genes related to biofilm formation and quorum sensing were enriched in S. natans VIII phages, indicating their potential to influence algal association in their bacterial hosts. In-vitro assays with a bacterial community harvested from sargassum surface biofilms and depleted of free viruses demonstrated that these bacteria are protected from lytic infection by seawater viruses but contain intact and inducible prophages. These bacteria form thicker biofilms when growing on sargassum-supplemented seawater compared to seawater controls, and phage induction using mitomycin C was associated with a significant decrease in biofilm formation. The induced metagenomes were enriched in genomic sequences classified as temperate viruses compared to uninduced controls. Conclusions: Our data shows that prophages contribute to the flexible genomes of S. natans VIII-associated bacteria. These prophages encode genes with symbiotic functions, and their induction decreases biofilm formation, an essential capacity for flexible symbioses between bacteria and the alga. These results indicate that prophage acquisition and induction contribute to genomic and functional diversification during sargassum-bacteria symbioses, with potential implications for algae growth. 1vVC6YGWLCm_DZc419o4RC Video Abstract [ABSTRACT FROM AUTHOR]

Background: As a subtype of pulmonary hypertension (PH), pulmonary veno-occlusive disease (PVOD) is devastating and life-threatening disease without effective therapy. Hydrogen has been reported to exhibits antioxidant and anti-inflammatory effects in a rat model induced by monocrotaline of PH. In this study, we investigated the effects of inhaled hydrogen gas on the prevention and treatment of PVOD induced by mitomycin C (MMC) in rats. Methods: PVOD was induced in female Sprague-Dawley rats through intraperitoneal injection of MMC at a concentration of 3 mg·kg− 1·wk− 1 for 2 weeks. Inhalation of hydrogen gas (H2) was administered through a designed rat cage concurrently or two weeks after MMC administration. The severity of PVOD was assessed by using hemodynamic measurements and histological analysis. The expression levels of general control nonderepressible 2 (GCN2), nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1) and endothelial-to-mesenchymal transition (EndoMT) related proteins in lung tissue were measured. Levels of lipid peroxidation pro-inflammatory cytokines in serum were determined. Results: Inhaled H2 improved hemodynamics and right heart function, reversed right ventricular hypertrophy, and prevented pulmonary vessel reconstitution in both prevention and treatment approaches. It decreased malondialdehyde (MDA) levels in the serum and the expression of NADPH oxidase 1 (NOX-1) in lung tissue. It regulated Nrf2/HO-1 signaling pathway and anti-inflammatory factor GCN2 in lung tissue, accompanied by a decrease in macrophages and pro-inflammatory cytokines. Our data suggested that H2 inhalation effectively countered EndoMT induced by MMC, as evidenced by the detection of endothelial markers (e.g., VE-cadherin and CD31) and mesenchymal markers (e.g., vimentin and fibronectin). Further research revealed that H2 preserved p-Smad3 and induced p-Smad1/5/9. Conclusion: Inhalation of H2 effectively inhibits the pathogenesis of PVOD induced by MMC in rats. This inhibitory effect may be attributed to the antioxidant and anti-inflammatory properties of H2. [ABSTRACT FROM AUTHOR]

Background: Although adjuvant gemcitabine (GEM) monotherapy improves the overall survival (OS) of patients with resected pancreatic cancer, its efficacy requires further improvement. This multicenter, phase II study investigated the efficacy of adjuvant portal vein infusion (PVI) chemotherapy followed by GEM therapy in patients with resected pancreatic cancer. Methods: 5‐fluorouracil (250 mg/day) and heparin (2000 IU/day) PVI chemotherapy were combined with systemic administration of mitomycin C (4 mg; days 6, 13, 20, and 27) and cisplatin (10 mg; days 7, 14, 21, and 28) for 4 weeks (PI4W), followed by GEM (1000 mg/m2; days 1, 8, and 15 every 4 weeks for 6 months). The primary endpoint was relapse‐free survival (RFS) and the secondary endpoints were OS and treatment completion. Results: Between November 2010 and August 2013, 53 patients who underwent complete resection were enrolled, including 30, 20, and 3 patients who underwent pancreaticoduodenectomies and distal and total pancreatectomies, respectively. In total, 51 (96.2%) patients underwent R0 resection, of whom 3, 2, 12, 35, 0, and 1 had stages IA, IB, IIA, IIB, III, and IV cancer, respectively, and 47 (88.7%) patients completed PI4W. The median RFS was 22.0 months (1‐, 3‐, 5, and 10 years RFS: 64.9%, 38.1%, 38.1%, and 38.1%, respectively), whereas the median OS was 32.0 months (1‐, 3‐, 5, and 10 years OS:86.6%, 47.2%, 44.4%, and 44.4%, respectively). Conclusion: Treatment with PI4W followed by GEM for 6 months after surgery may be beneficial in patients undergoing curative resection of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Introduction: Routine blood tests are prognostic tests for patients with cholangiocarcinoma. New drug regimens may produce a median overall survival of 2 years or more. Methods: This single practice, IRB-approved, phase II trial examines prognostic tests, Kaplan-Meier survival, and univariate Cox regression analyses. Eligibility requires: intent-to-treat; signed consent; advanced measurable intrahepatic cholangiocarcinoma, with or without resistance to the test drugs; any adult age; performance status 0-2; and expected survival of = 6 weeks. Biweekly treatment, with 1/3 of standard dosages in mg/M2, includes: Gemcitabine 500; 5-Fluorouracil 1200 over 24 hours; Leucovorin 180; Irinotecan 80; and on day 2, Oxaliplatin 40. On progression, drugs are added on day 2: first, Docetaxel 25 precedes Oxaliplatin, with or without Mitomycin C 6 after Oxaliplatin. The next sequential additions are day 1, Cetuximab 400 total mg, then 200 mg weekly, and then Bevacizumab 10 mg/kg is substituted for Cetuximab (FDA IND# 119005). Results: For 35 patients, 19 with 1-2 lines of prior therapy, resistant tumors, and 16 no prior therapy, survival at 24-months is = 72 and = 58%, respectively. For 14 patients aged = 70 years, = 63% survive 24 months, P = 0.28. Validated tests that predict = 6-month survivals find median survival times of 17-months through > 2-years when compared to patients with favorable tests: Neutrophils lymphocyte ratio > 3.0, HR = 6.54, P < 6.4x10-3; absolute neutrophil count > 8000/ml, HR = 4.95, P < 6.5x10-3; serum albumin < 3.5 g/dl, HR = 4.10, P < 0.03; and lymphocyte monocyte ratio< 2.1, HR = 1.6, P = 0.50. Overall, the 76 (60-90)% of patients with 0-2 out of 4 high risk tests survive = 24 months, (P = 7.1x10-3). Treatments produce neither hospitalization, neutropenic fever, severe enteritis, nor severe neuropathies. Conclusion: Two-year survival is replicable and predictable. Findings warrant phase III validation tests of sequential regimens, re-challenge with recombination, low dosages, and blood tests that are associated with lethal mechanisms that impair response and survival. [ABSTRACT FROM AUTHOR]

Background/aim: To compare the efficacy of topical 0.05% cyclosporine A (CsA) and 0.1% topical cyclosporine A (CsA) over a 6-month period following pterygium surgery, specifically evaluating their effects on postoperative recurrence and clinical parameters. Material and methods: This clinical study enrolled 245 patients with pterygium who underwent surgery using the conjunctival autograft technique with mitomycin C (MMC) were enrolled. Participants were divided into three groups: Group 1 (0.05% CsA) (n = 80), Group 2 (0.1% CsA) (n = 80), and a control group (n = 85). They were examined at postoperative first day, first week, first month and sixth month. The examination included best corrected visual acuity (BCVA), intraocular pressure (IOP), presence of inflammation, and ptergium recurrence, all of which were compared across the groups. Results: The mean age of the patients was 63.22 ± 9.39 years, with 53.3% male and 46.7% female. The three groups were similar in terms of demographic characteristics and pterygium size. Inflammation in surgical area significantly regressed in all groups at 6 months postoperatively (p < 0.05). Inflammation in the first and sixth months was not different between the groups (p = 0.118, p = 0.580, and p = 0.435, respectively). The recurrence rate was not different between groups (p = 0.890). There was no statistically significant difference between groups regarding IOP (p = 0.818). A significant increase in BCVA after surgery was observed in three groups compared to preoperative levels (p < 0.05). Conclusion: This study showed that there was no difference between the efficacy of 6 month topical 0.05% CsA and 0.1% CsA application after pterygium surgery with the conjunctival autograft technique with MMC on postoperative outcomes. Including postoperative recurrence, IOP changes, BCVA changes and surgical area inflammation. [ABSTRACT FROM AUTHOR]

In this work, we developed multifunctional hydrogel nanoparticles (NPs) that can encapsulate anticancer drugs and imaging contrast agents as well. Mitomycin C (MMC) and rhodamine B (RB) were selected as models for anticancer drugs and imaging contrasting agents, respectively. Both MMC and RB were linked to the succinated polyvinyl alcohol polymer (PVA-SA). The selected labeled hydrogel NPs ((0.5% RB)-PVA-SA NPs and (1.5% RB)-PVA-SA NPs) improved the RB quantum yield from 29.8% to a minimum of 42.7%. Moreover, they showed higher emission stability compared to free RB when they were repeatedly excited at 554 nm for 2 h. Furthermore, the dye polymeric interactions significantly increased the RB fluorescence lifetime by approximately twofold. All these optical properties pave the way for our labeled hydrogel NPs to be used in imaging-guided therapy. For the labeled MMC-loaded NPs, the MMC-binding efficiency was found to be exceedingly high in all synthesized samples: a minimum of 92% was achieved. In addition, the obtained pH-dependent drug release profiles as well as the cytotoxicity evaluation demonstrated the high potential of releasing MMC under acidic cancerous conditions. Moreover, the in vitro cellular uptake experiment confirmed the accumulation of MMC NPs throughout the cytoplasm. [ABSTRACT FROM AUTHOR]

Objective: To develop machine learning (ML) models, using pre and intraoperative surgical parameters, for predicting trabeculectomy outcomes in the eyes of patients with juvenile‑onset primary open‑angle glaucoma (JOAG) undergoing primary surgery. Subjects: The study included 207 JOAG patients from a single center who met the following criteria: diagnosed between 10 and 40 years of age, with an IOP of >22 mmHg in the eyes on two or more occasions, open angle on gonioscopy in both eyes, with glaucomatous optic neuropathy, and requiring a trabeculectomy for IOP control. Only the patients with a minimum 5‑year follow‑up after surgery were included in the study. Methods: A successful surgical outcome was defined as IOP ≤18 mmHg (criterion A) or 50% reduction in IOP from baseline (criterion B) 5 years after trabeculectomy. Feature selection techniques were used to select the most important contributory parameters, and tenfold cross‑validation was used to evaluate model performance. The ML models were evaluated, compared, and prioritized based on their accuracy, sensitivity, specificity, Matthew correlation coefficient (MCC) index, and mean area under the receiver operating characteristic curve (AUROC). The prioritized models were further optimized by tuning the hyperparameters, and feature contributions were evaluated. In addition, an unbiased relationship analysis among the parameters was performed for clinical utility. Results: Age at diagnosis, preoperative baseline IOP, duration of preoperative medical treatment, Tenon’s thickness, scleral fistulation technique, and intraoperative mitomycin C (MMC) use, were identified as the main contributing parameters for developing efficient models. The three models developed for a consensus‑based outcome to predict trabeculectomy success showed an accuracy of >86%, sensitivity of >90%, and specificity of >74%, using tenfold cross‑validation. The use of intraoperative MMC and a punch for scleral fistulation compared to the traditional excision with scissors were significantly associated with long‑term success of trabeculectomy. Conclusion: Optimizing surgical parameters by using these ML models might reduce surgical failures associated with trabeculectomy and provide more realistic expectations regarding surgical outcomes in young patients. [ABSTRACT FROM AUTHOR]

AimTo evaluate the safety and efficacy of posterior scleral application (a modified technique) of an antimetabolite mitomycin C-soaked sponge in trabeculectomy for patients with glaucoma.MethodsThis retrospective study included 101 patients (115 eyes) with glaucoma (aged 12-83y) who underwent trabeculectomy using a modified mitomycin C-soaked sponge placement method. A piece of 3.5×10 mm2 sponge was placed vertically and posteriorly with the long side perpendicular to the limbus. The mitomycin C concentration and exposure time were 0.2-0.5 mg/mL and 1-5min, respectively. Intraocular pressure, best-corrected visual acuity, and hypotensive medications were recorded at baseline and at the final visit. Complications, interventions required, and bleb morphology were recorded postoperatively. The primary outcome was trabeculectomy safety, including complications and bleb morphology; the secondary outcome was the trabeculectomy success rate.ResultsAt the final follow-up [median 28mo, range 7-67mo and interquartile range (IQR) 13mo], the qualified (cumulative) success rate was 93.0% and the complete success rate was 60.0%. No bleb-related complications were observed. The mean height, extent, and vascularity grades were 0.6±0.9, 1.1±0.4, and 2.4±0.9, respectively. All Seidel tests were negative. The mean posteriority grade was 0.8±0.4.ConclusionTrabeculectomy with the long side of a mitomycin C-soaked sponge placed perpendicular to the corneal limbus is safe and effective.

To describe visual field outcomes in the Primary Tube Versus Trabeculectomy (PTVT) Study. Cohort analysis. A total of 155 eyes (155 subjects) randomly assigned to treatment with tube shunt surgery (n = 84) or trabeculectomy with mitomycin C (n = 71). The PTVT Study was a multicenter randomized clinical trial comparing the safety and efficacy of trabeculectomy and tube shunt surgery in eyes without previous intraocular surgery. Subjects underwent standard automated perimetry (SAP) at baseline and annually for 5 years. Standard automated perimetry tests were deemed reliable if the false-positive rate was ≤ 15%. Tests were excluded if visual acuity was ≤ 20/400 or loss of ≥ 2 Snellen lines from baseline because of a nonglaucomatous etiology. Linear mixed-effects models were used to compare rates of change in SAP mean deviation (MD) between the 2 groups. Intraocular pressure (IOP) control was assessed by percentage of visits with IOP < 18 mmHg and mean IOP. Rate of change in SAP MD during follow-up. A total of 730 SAP tests were evaluated (average of 4.7 tests per eye). The average SAP MD at baseline was –12.8 ± 8.3 decibels (dB) in the tube group and –12.0 ± 8.4 dB in the trabeculectomy group (P = 0.57). The mean rate of change in SAP MD was –0.32 ± 0.39 dB/year in the trabeculectomy group and –0.47 ± 0.43 dB/year in the tube group (P = 0.23). Eyes with mean IOP 14 to 17.5 mmHg had significantly faster rates of SAP MD loss compared with eyes with mean IOP < 14 mmHg (–0.59 ± 0.13 vs. –0.27 ± 0.08 dB/year; P = 0.012), and eyes with only 50% to 75% of visits with IOP < 18 mmHg had faster rates than those with 100% of visits with IOP < 18 mmHg (–0.90 ± 0.16 vs. –0.29 ± 0.08 dB/year; P < 0.001). Multivariable analysis identified older age and worse IOP control as risk factors for faster progression in both treatment groups. No statistically significant difference in mean rates of visual field change was observed between trabeculectomy and tube shunt surgery in the PTVT Study. Worse IOP control was significantly associated with faster rates of SAP MD loss during follow-up. Older patients were also at risk for faster progression. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Background: Ocular surface squamous neoplasia (OSSN) includes a wide spectrum of conjunctival and corneal intraepithelial neoplasia, which can manifest as mild, moderate, severe dysplasia, carcinoma-in-situ and invasive squamous cell carcinoma. OSSN can mimic many common indolent lesions like pterygium and have a potential for causing ocular and systemic morbidity and mortality. OSSN is more common in elderly males. ultraviolet-B light, human immune deficiency, and human papilloma virus have been proposed as major risk factors in aetiopathogenesis. Though diagnosis of OSSN is mainly based on clinical suspicion, definitive diagnosis needs histopathological evaluation. Anterior segment optical coherence tomography, ultrasonic bio microscopy, and impression cytology are nonsurgical tools used for diagnosis and management, of which anterior segment optical coherence tomography has brought about a paradigm shift in the diagnosis of OSSN. Aim: The aim of the study was to demonstrate the demographics, clinical profile, types of OSSN, management approaches, histopathology and the effectiveness of different approaches in patients with OSSN in a tertiary care centre in Tamil Nadu. Materials and Methods: It was a hospital-based prospective interventional study where 51 eyes of 50 patients with clinically suspicious OSSN were studied between July 2021 and January 2023 (over 18 months) with a minimum follow-up of 6 months. Results: The age group for the patients ranged between 30 and 79 years. Out of 50 patients, 26 were men and 24 were women with no sex predilection in our study. Unilateral involvement was seen in 49 patients and only one patient had bilateral involvement. Twenty-nine patients presented with gelatinous-like lesions, six with leukoplakic lesions, five with papilliform like lesion, nine with pigmented lesions and one with nodulo ulcerative type lesion. On histopathological examination, majority (21 patients) were severe dysplasia. Majority (78.4%) underwent surgical clearance with no recurrence. Adjunctive therapy to reduce recurrence included intraoperative cryotherapy and postoperative topical chemotherapy using mitomycin C. Conclusion: In our series, the most common morphological type of lesion was gelatinous, and surgical management using Shield’s technique was commonly used as the management option for unifocal lesions less than 5 mm with less than 4 clock hours involvement. The demographic profile was comparable with other studies on OSSN. Being a potentially malignant condition, a study on OSSN helps us in understanding the disease better and helps in early detection, leading to timely intervention and improved treatment outcomes. Furthermore, research on OSSN contributes to enhancing our knowledge on ocular oncology.

AIM: To investigate the clinical efficacy and safety of XEN drainage tube implantation combined with mitomycin C(MMC)for open angle glaucoma(OAG).METHODS:A total of 37 OAG patients(37 eyes)were retrospectively included, grouped by anti-glaucoma surgical treatment as the first choice or not, with 17 patients(17 eyes)in the group with primary surgical treatment, and 20 patients(20 eyes)in the group with the numerous surgeries. The intraocular pressure(IOP), kinds of IOP-lowering drugs, and complications were collected and analyzed in 1 a follow-up postoperatively.RESULTS:Upon the one-year follow-up, IOP had decreased from 27.56±9.94, 28.43±14.18 mmHg to 15.16±3.65, 17.18±5.83 mmHg in both groups, respectively, representing a reduction of 55.01% and 60.43%, respectively(t=4.863, P

Introduction: Bacterial infections and the rising antimicrobial resistance pose a significant threat to public health. Pseudomonas aeruginosa produces bacteriocins like pyocins, especially S-type pyocins, which are promising for biological applications. This research focuses on clinical P. aeruginosa isolates to assess their bacteriocin production, inhibitory spectrum, chemical structure, antibacterial agents, and preservative potential. Methods: The identification of P. aeruginosa was conducted through both phenotypic and molecular approaches. The inhibitory spectrum and antibacterial potential of the isolates were assessed. The kinetics of antibacterial peptide production were investigated, and the activity of bacteriocin was quantified in arbitrary units (AU ml−1). Physico-chemical characterization of the antibacterial peptides was performed. Molecular weight estimation was carried out using SDS–PAGE. qRT-PCR analysis was employed to validate the expression of the selected candidate gene. Result: The antibacterial activity of P. aeruginosa was attributed to the secretion of bacteriocin compounds, which belong to the S-type pyocin family. The use of mitomycin C led to a significant 65.74% increase in pyocin production by these isolates. These S-type pyocins exhibited the ability to inhibit the growth of both Gram-negative (P. mirabilis and P. vulgaris) and Gram-positive (S. aureus, S. epidermidis, E. hirae, S. pyogenes, and S. mutans) bacteria. The molecular weight of S-type pyocin was 66 kDa, and its gene expression was confirmed through qRT-PCR. Conclusion: These findings suggest that S-type pyocin hold significant potential as therapeutic agents against pathogenic strains. The Physico-chemical resistance of S-type pyocin underscores its potential for broad applications in the pharmaceutical, hygiene, and food industries. [ABSTRACT FROM AUTHOR]

Purpose: To investigate gel stent implantation with and without intraoperative sustained-release mitomycin C (MMC SR) in a rabbit model for gel stent implantation, and to examine aqueous humor outflow (AHO) postimplantation. Methods: Four groups of rabbits were included. Group 1 was untreated (control). Groups 2, 3, and 4 received the gel stent without MMC, with MMC solution (subconjunctival injection), and with MMC SR (subconjunctival injection), respectively. Intraocular pressure (IOP) and AHO were assessed via tonometry and indocyanine green-based angiography, respectively. The main efficacy measure was change in IOP from baseline. Results: Following gel stent implantation, Groups 2, 3, and 4 maintained ≥20% IOP reduction (response) for a median duration of 1 week, 6.5 weeks, and 30 weeks, respectively. Angiography showed normal aqueous humor drainage (Group 1) beginning at the perilimbal trabecular plexus and continuing posteriorly to episcleral outflow vessels. Following implantation, drainage occurred preferentially and directly into the subconjunctival bleb. Conclusions: Gel stent implantation with MMC SR was most effective in achieving sustained, long-term IOP reduction in the rabbit model, compared with implantation with or without MMC solution. Bleb presence and the postimplantation aqueous angiography results indicated redirection of the AHO to the subconjunctival vasculature and presumed lymphatics, suggesting efficient glaucoma filtration to lower IOP in this model. This rabbit model and aqueous angiography may help refine understanding of the mechanism of action of minimally invasive glaucoma surgeries and ultimately translate to improved surgical devices and procedures for patients with glaucoma. [ABSTRACT FROM AUTHOR]

The level of cytokine expression was measured in human coronary artery (HCAEC) and internal thoracic artery (HITAEC) endothelial cells exposed to 500 ng/ml alkylating mutagen mitomycin C (MMC) and 5 μM atorvastatin. It was found that treatment of MMC-exposed HCAEC with atorvastatin decreased secretion of macrophage migration inhibitory factor (MIF), IL-8, and IL8 gene expression, but increased the expression of SERPINE1 gene encoding the PAI-1 protein. In atorvastatin-treated HITAEC, the concentration of MIF protein and the expression of the IL8 and SERPINE1 genes were reduced. We can conclude that atorvastatin prevents proinflammatory activation of endothelial cells cultured under conditions of genotoxic load. However, the molecular mechanisms of this effect require further research. [ABSTRACT FROM AUTHOR]

BACKGROUND: In recent years, there have been many novel tympanic membrane repair materials, including patches and 3D-printed scaffolds. However, the tympanic membrane repaired by these materials is different from the natural tympanic membrane in terms of thickness and internal structure. OBJECTIVE: To explore the efficacy of bone marrow mesenchymal stem cells-loaded high-porosity polycaprolactone/collagen nanofiber membrane scaffolds in repairing chronic tympanic membrane perforation. METHODS: Polycaprolactone, polycaprolactone-collagen, and high-porosity polycaprolactone-collagen nanofiber membranes were prepared by electrospinning technology, and the surface morphology, porosity and cell compatibility of the scaffolds were characterized. The tympanic membrane perforation model of 50 male SD rats was established by puncturing the posterior lower part of both eardrums with a sterile 23-measure needle combined with mitomycin C and hydrocortisone. After 12 weeks of modeling, the rats were divided into five groups by the random number table method. The blank control group did not receive any treatment. In the other four groups, polycaprolactone nanofiber membrane (polycaprolactone group), polycaprolactone-collagen nanofiber membrane (polycaprolactone-collagen group), high-porosity polycaprolactone-collagen nanofiber membrane (high-porosity polycaprolactone-collagen group) and high-porosity polycaprolactone-collagen nanofiber membrane containing bone marrow mesenchymal stem cells (high-porosity polycaprolactone-collagen group) were implanted at the perforation of the tympanic membrane, respectively. Each group consisted of 10 animals. The healing of the tympanic membrane was examined by otoendoscopy after 1, 2, 3 and 4 weeks of stent implantation. Hematoxylin-eosin staining, Masson staining, and Ki-67 immunohistochemical staining were performed on the tympanic membrane after 4 weeks of implantation. RESULTS AND CONCLUSION: (1) Scaffold characterization: Scanning electron microscopy showed that compared with other nanofiber membranes, the highporosity polycaprolactone-collagen nanofiber membranes had more orderly nanofiber structure, larger surface pore size, and higher porosity (P < 0.001). Live/ dead staining showed that bone marrow mesenchymal stem cells adhered well on the three scaffolds, and the number of living cells on the high-porosity polycaprolactone-collagen nanofiber membrane was more than that on the other two scaffolds. Almarin staining showed that the proliferation rate of bone marrow mesenchymal stem cells on the high-porosity polycaprolactone-collagen nanofiber membrane was higher than that of the other two fiber membranes. (2) Animal experiments: Except for the blank control group, the tympanic membrane of the other four groups healed gradually with the extension of the time of fibrous membrane implantation, among which the healing speed of the cell-loaded high-porosity polycaprolactone-collagen group was the fastest. Hematoxylin-eosin staining, Masson staining, and Ki-67 immunohistochemical staining showed that the tympanic membrane of rats in the cell-carrying highporosity polycaprolactone-collagen group was moderate in thickness and a three-layer structure with uniform collagen fiber layers, similar to the normal tympanic membrane, and the repair quality of tympanic membrane was better than that of other fiber membrane groups. (3) The results showed that the high-porosity polycaprolactone-collagen nanofiber membrane containing bone marrow mesenchymal stem cells could not only rapidly repair the perforation of the tympanic membrane, but also the newly healed tympanic membrane was similar to normal tympanic membrane in structure and thickness. [ABSTRACT FROM AUTHOR]

Chronic tympanic membrane perforation represents a prevalent otological condition, necessitating a reliable animal model for the validation and safety assessment of surgical techniques and materials employed in myringoplasty. This prospective study involved the establishment of chronic tympanic membrane perforation animal models in 16 chinchillas. A thermic myringotomy was conducted on the right ear (study group), followed by cold instrument myringotomy, coupled with the topical application of mitomycin C and dexamethasone solution on the left ear (control group). Results revealed that tympanic membrane perforations in the study group persisted for a minimum of 4 weeks in 93.7% of cases and extended to 12 weeks in 62.5% of the cases. In contrast, all tympanic membrane perforations in the control group were present at 4 weeks, with only 37.5% persisting after 12 weeks, although statistical tests did not find significant differences between the two groups (chi-square: p-value = 0.157, Kruskal–Wallis: p-value = 0.093, Mann–Whitney: p-value = 0.121). The thermic myringotomy employed to induce chronic tympanic membrane perforation in animals demonstrated efficiency and sustainability. This model, characterized by stability and reproducibility, holds promise for future experimental applications in the field. [ABSTRACT FROM AUTHOR]

Objective: Aplastic anemia is a rare condition characterized by bone marrow failure due to various etiologies including Fanconi anemia. Mitomycin C is an alkylating agent inducing chromosome breaks in. aplastic anemia. The clastogenic effect of mitomycin C is most marked in Fanconi anemia. This study aims to demonstrate mitomycin C induced chromosomal breaks in patients with aplastic anemia and distinguish Fanconi anemia patients among them. Material and Method: Clastogenicity test was applied to 147 patients with aplastic anemia, four siblings and 30 healthy controls. Both simultaneous and mitomycin C (MMC) treated lymphocyte cultures were prepared. Chromosome breaks per metaphase were calculated and cytogenetic abnormalities were analyzed. Results: The mean number of chromosome breaks per metaphase increased from 0.02 to 0.37 after MMC treatment in patients with aplastic anemia. This number changed only from 0.01 to 0.16 in the healthy controls. In 25 patients (16.6%), the number of chromosome breaks per metaphase was > 1 in MMC treated cultures, and MMC treatment induced a significant increase compared to spontaneous culture (2.88 vs 0.35), which assured the diagnosis of Fanconi anemia. We observed various multiple chromosomal aberrations in all of them and accompanying phenotypic features in 20. Conclusion: Mitomycin C induced chromosomal breaks and cytogenetic abnormalities enable the diagnostic differentiation between aplastic anemia and Fanconi anemia. [ABSTRACT FROM AUTHOR]

Excessive fibrosis and resultant poor control of intraocular pressure (IOP) reduce the efficacy of glaucoma surgeries. Historically, corticosteroids and anti-fibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5-FU), have been used to mitigate post-surgical fibrosis, but these have unpredictable outcomes. Therefore, there is a need to develop novel treatments which provide increased effectiveness and specificity. This review aims to provide insight into the pathophysiology behind wound healing in glaucoma surgery, as well as the current and promising future wound healing agents that are less toxic and may provide better IOP control. [ABSTRACT FROM AUTHOR]

Colicin (Col) plasmid contains colicin encoding genes arranged in an operon controlled by an SOS inducible promoter. Therefore, any external stresses to the host cell can induce the expression of the downstream genes in the Col operon, including a lysis gene. The lysis protein is involved in the extracellular release of colicin through lysis of the producer cells, which causes a decline in culture turbidity. However, it is not yet known that E. coli cells with the native pColE9-J plasmid hold the same level of cell death at the population level following a set of induced conditions. In this study, using a mitomycin C sensitivity assay along with a live dead staining method of detection, we showed that the native pColE9-J plasmid, which unusually carries an extended Col operon (ColE9) containing two lysis genes, did not confer a rapid decline in the culture turbidity following induction with mitomycin C. Interestingly a subset of the cells suffered perturbation of their outer membrane, which was not observed from single lysis mutant (∆ celE or ∆ celI) cells. This observed heterogeneity in the colicin E9 release leading to differential outer membrane perforation may bring a competitive advantage to these cells in a mixed population. [ABSTRACT FROM AUTHOR]

Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise the therapeutic potential of drugs, thereby reducing the effective dose and consequently the pharmacological burden of the medication. We recently demonstrated that it is possible to significantly increase the therapeutic efficacy of mitomycin C against a bladder carcinoma cell line by exposure to non-toxic doses of blue light (453 nm). In the present study, we investigated whether the therapeutically supportive effect of blue light can be further enhanced by the additional use of the wavelength-specific photosensitiser riboflavin. We found that the gemcitabine-induced cytotoxicity of bladder cancer cell lines (BFTC-905, SW-1710, RT-112) was significantly enhanced by non-toxic doses of blue light in the presence of riboflavin. Enhanced cytotoxicity correlated with decreased levels of mitochondrial ATP synthesis and increased lipid peroxidation was most likely the result of increased oxidative stress. Due to these properties, blue light in combination with riboflavin could represent an effective therapy option with few side effects and increase the success of local treatment of bladder cancer, whereby the dose of the chemotherapeutic agent used and thus the chemical load could be significantly reduced with similar or improved therapeutic success. [ABSTRACT FROM AUTHOR]

Background: Neovascular glaucoma (NVG) is an irreversible blinding eye disease worldwide and is classified as one of the refractory glaucoma conditions, severely impacting visual function and vision. Unfortunately, effective surgical interventions to improve the prognosis of NVG patients are currently lacking. The study aims to evaluate the efficacy and safety of anterior chamber proliferative membrane interception (AC-PMI)-enhanced trabeculectomy compared to the traditional trabeculectomy. Methods: AC-PMI enhanced trabeculectomy versus trabeculectomy for the treatment of NVG is a single-center, prospective, double-arms, and randomized controlled trial of superior efficacy, which will involve 100 NVG inpatients. Patients will be randomly assigned into two groups using the random number table method. One group will undergo trabeculectomy using anti-vascular endothelial growth factor (Anti-VEGF) preoperatively and mitomycin C intraoperatively, while the other group will undergo AC-PMI enhanced trabeculectomy with the same medications (Anti-VEGF and mitomycin C). The patients will be followed up at the baseline and 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months postoperatively. Meanwhile, we will collect the demographics, characteristics, and examination results and monitor any occurrences of adverse events at each follow-up time. Discussion: This is an efficacy study of a novel surgical approach for treating neovascular glaucoma. Building upon conventional filtering surgeries, this approach introduces an additional step involving the interception of the proliferative membrane to effectively halt the growth of fibrovascular tissue. This study aims to explore a promising new surgical approach for managing NVG and contribute to the advancement of glaucoma treatment strategies. Trial registration: ChiCTR ChiCTR2200055138. Registered on 01 January 2022. https://www.chictr.org.cn/showproj.html?proj=145255. [ABSTRACT FROM AUTHOR]

Background and Purpose: The mammalian target of rapamycin (mTOR) pathway plays critical roles in intrinsic chemoresistance by regulating Fanconi anaemia complementation group D2 (FANCD2) expression. However, the mechanisms by which mTOR regulates FANCD2 expression and related inhibitors are not clearly elucidated. Extracts of Centipeda minima (C. minima) showed promising chemosensitizing effects by inhibiting FANCD2 activity. Here, we have aimed to identify the bioactive chemosensitizer in C. minima extracts and elucidate its underlying mechanism. Experimental Approach: The chemosensitizing effects of arnicolide C (ArC), a bioactive compound in C. minima, on non‐small cell lung cancer (NSCLC) were investigated using immunoblotting, immunofluorescence, flow cytometry, the comet assay, small interfering RNA (siRNA) transfection and animal models. The online SynergyFinder software was used to determine the synergistic effects of ArC and chemotherapeutic drugs on NSCLC cells. Key Results: ArC had synergistic cytotoxic effects with DNA cross‐linking drugs such as cisplatin and mitomycin C in NSCLC cells. ArC treatment markedly decreased FANCD2 expression in NSCLC cells, thus attenuating cisplatin‐induced FANCD2 nuclear foci formation, leading to DNA damage and apoptosis. ArC inhibited the mTOR pathway and attenuated mTOR‐mediated expression of E2F1, a critical transcription factor of FANCD2. Co‐administration of ArC and cisplatin exerted synergistic anticancer effects in the A549 xenograft mouse model by suppressing mTOR/FANCD2 signalling in tumour tissues. Conclusion and Implications: ArC suppressed DNA cross‐linking drug‐induced DNA damage response by inhibiting the mTOR/E2F1/FANCD2 signalling axis, serving as a chemosensitizing agent. This provides insight into the anticancer mechanisms of ArC and offers a potential combinatorial anticancer therapeutic strategy. [ABSTRACT FROM AUTHOR]

The global pathogen Clostridioides difficile is a well-studied organism, and researchers work on unraveling its fundamental virulence mechanisms and biology. Prophages have been demonstrated to influence C. difficile toxin expression and contribute to the distribution of advantageous genes. All these underline the importance of prophages in C. difficile virulence. Although several C. difficile prophages were sequenced and characterized, investigations on the entire active virome of a strain are still missing. Phages were mainly isolated after mitomycin C-induction, which does not resemble a natural stressor for C. difficile. We examined active prophages from different C. difficile strains after cultivation in the absence of mitomycin C by sequencing and characterization of particleprotected DNA. Phage particles were collected after standard cultivation, or after cultivation in the presence of the secondary bile salt deoxycholate (DCA). DCA is a natural stressor for C. difficile and a potential prophage-inducing agent. We also investigated differences in prophage activity between clinical and non-clinical C. difficile strains. Our experiments demonstrated that spontaneous prophage release is common in C. difficile and that DCA presence induces prophages. Fourteen different, active phages were identified by this experimental procedure. We could not identify a definitive connection between clinical background and phage activity. However, one phage exhibited distinctively higher activity upon DCA induction in the clinical strain than in the corresponding non-clinical strain, although the phage is identical in both strains. We recorded that enveloped DNA mapped to genome regions with characteristics of mobile genetic elements other than prophages. This pointed to mechanisms of DNA mobility that are not well-studied in C. difficile so far. We also detected phage-mediated lateral transduction of bacterial DNA, which is the first described case in C. difficile. This study significantly contributes to our knowledge of prophage activity in C. difficile and reveals novel aspects of C. difficile (phage) biology. [ABSTRACT FROM AUTHOR]

The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC. The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine‐Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases. Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P <.05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P =.05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P =.46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P >.05). The median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR, 0.71 [0.53-0.95]; P =.02), increased PFS (HR, 0.66 [0.51-0.87]; P =.003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P =.004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P =.009). Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC. [ABSTRACT FROM AUTHOR]

Mitomycin C (MMC)-induced genotoxic stress can be considered to be a novel trigger of endothelial dysfunction and atherosclerosis—a leading cause of cardiovascular morbidity and mortality worldwide. Given the increasing genotoxic load on the human organism, the decryption of the molecular pathways underlying genotoxic stress-induced endothelial dysfunction could improve our understanding of the role of genotoxic stress in atherogenesis. Here, we performed a proteomic profiling of human coronary artery endothelial cells (HCAECs) and human internal thoracic endothelial cells (HITAECs) in vitro that were exposed to MMC to identify the biochemical pathways and proteins underlying genotoxic stress-induced endothelial dysfunction. We denoted 198 and 71 unique, differentially expressed proteins (DEPs) in the MMC-treated HCAECs and HITAECs, respectively; only 4 DEPs were identified in both the HCAECs and HITAECs. In the MMC-treated HCAECs, 44.5% of the DEPs were upregulated and 55.5% of the DEPs were downregulated, while in HITAECs, these percentages were 72% and 28%, respectively. The denoted DEPs are involved in the processes of nucleotides and RNA metabolism, vesicle-mediated transport, post-translation protein modification, cell cycle control, the transport of small molecules, transcription and signal transduction. The obtained results could improve our understanding of the fundamental basis of atherogenesis and help in the justification of genotoxic stress as a risk factor for atherosclerosis. [ABSTRACT FROM AUTHOR]

Introduction: The current treatment of non-muscle-invasive bladder cancer is suboptimal. However, in recent years, hyperthermia intravesical chemotherapy (HIVEC) has emerged as a more effective alternative to conventional bladder perfusion. This novel treatment approach appears to have a similar therapeutic effect as Bacillus Calmette-Guérin (BCG) perfusion. This study aims to evaluate the safety and effectiveness of HIVEC compared to conventional bladder perfusion chemotherapy for non-muscle-invasive bladder cancer. Additionally, it aims to evaluate the safety and effectiveness of HIVEC in comparison to BCG perfusion therapy for non-muscle-invasive bladder cancer. Methods: We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science databases to gather relevant studies on HIVEC for non-muscle-invasive bladder cancer. The analysis of the collected data was carried out using RevMan 5.3 software. Results: A total of 8 randomized controlled trials were included in this meta-analysis, involving 1,203 patients. Among them, 629 cases received HIVEC, 419 cases received conventional bladder perfusion chemotherapy with mitomycin C, and 155 cases received BCG. The combined analysis revealed that the recurrence rate of bladder hyperthermic perfusion was significantly lower than that of conventional perfusion chemotherapy (RR = 0.65, 95% CI: 0.52, 0.82, p = 0.0003). However, there was no significant difference in recurrence rate between HIVEC and BCG perfusion (RR = 0.78, 95% CI: 0.56, 1.09, p = 0.14). Furthermore, no significant difference was found in the progression rate between the HIVEC group and either the conventional bladder chemotherapy group (RR = 1.08, 95% CI: 0.52, 2.26, p = 0.83) and the BCG perfusion group (RR = 0.48, 95% CI: 0.19, 1.25, p = 0.13). However, compared with the conventional bladder perfusion chemotherapy group, there was no significant statistical difference in adverse events between the bladder hyperthermia chemotherapy group and the conventional bladder perfusion chemotherapy group (RR 1.08, 95% CI: 0.80, 1.45, p = 0.63). No significant difference in the incidence of adverse events was observed between HIVEC and BCG perfusion (RR 1.03, 95% CI: 0.83, 1.29, p = 0.79). Conclusion: The existing results indicate that HIVEC, when compared to conventional bladder perfusion chemotherapy, can lower the recurrence rate of non-muscle-invasive bladder cancer. However, it does not significantly affect the progression rate. There was no statistically significant difference observed in the incidence of adverse events between the use of HIVEC and conventional chemotherapy. Additionally, there was no significant difference in the recurrence rate, progression rate, and incidence of adverse events when compared to BCG. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Fanconi anemia with Mitomycin C sensitivity is a rare, complex hematological condition. Our case study emphasizes the significance of early diagnosis, appropriate genetic testing, and cautious use of chemotherapeutic agents. Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure, congenital anomalies, and predisposition to cancer. Here, we present the case of a 6‐year‐old boy with a known diagnosis of Fanconi anemia who exhibited sensitivity to Mitomycin C. The patient had a history of recurrent blood transfusions due to anemia and was referred to our institution following worsening symptoms, including pallor, swelling in limbs, and respiratory distress. Physical examination revealed characteristic features of FA such as mesomelia, low‐set ears, hyperpigmented macules, microcephaly, micropthalmos, and thumb hypoplasia. Imaging studies demonstrated bilateral radial hypoplasia and congenital agenesis of the left kidney. Laboratory investigations revealed pancytopenia, aberrant liver function tests, and elevated inflammatory markers. Importantly, the patient exhibited sensitivity to Mitomycin C, highlighting the necessity for caution in selecting chemotherapeutic agents in FA patients. This case underscores the importance of early recognition, comprehensive evaluation, and tailored management strategies of patients with Fanconi anemia to optimize outcomes and minimize complications. [ABSTRACT FROM AUTHOR]

Background: We have been conducting a collaborative study on the thresholds of mutagens. In our previous examinations of cell activity and cell proliferation as endpoints, both displayed hormesis. This time, we conducted experiments to determine thresholds using the micronucleus test as an endpoint. Methods: The micronucleus test was conducted using Chinese hamster CHL/IU cells and mouse lymphoid L5178Y cells. Additionally, we conducted preliminary investigations into the gene expression using human TK6 cells. Results: When adhesive CHL/IU cells were treated with mitomycin C (MMC), and the hormetic response was examined, hormesis was not observed clearly. When L5178Y cells were treated with methyl methanesulfonate (EMS), AF-2, MMC, and colchicine, all of them exhibited an adaptive response. Additionally, cross-adaptive responses using AF-2 and MMC or EMS and MMC were conducted, both combinations showed a cross-adaptive response. When the gene expression patterns of six genes were investigated by RT-PCR after treatment with MMC, EMS, and H2O2 using TK6 cells, two genes, GADD45 A and P21, were induced in a dose- and time-dependent manner. Conclusion: Adaptive responses arise from preconditioning. As hormesis is inherently linked to preconditioning, adaptive responses observed in this study strongly suggest that hormesis was induced, hence existence of thresholds. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The aim was to assess changes in physical parameters of subglottic stenosis (SGS) following serial endoscopic surgical intervention. Study Design: This was a retrospective chart review. Methods: A retrospective review of 52 idiopathic subglottic stenosis (iSGS) patients undergoing multiple endoscopic (excision/dilation) procedures between 2014 and 2022 was completed. Parameters including proximal stenosis distance from the vocal process and total stenosis length collected intraoperatively were compared over serial treatments. Differences between patient variables affecting distances from the vocal process and mean stenosis length were statistically analyzed utilizing nonparametric estimators including the Mann Whitney U, Fisher exact, and linear regression models. Results: For the cohort of iSGS patients (N = 52), the mean age was 55.1 (±15.1). The patients were predominantly female (96.2%) and Caucasian (84.6%). Patients underwent an average of 3.4 (±1.3) endoscopic procedures for long‐term treatment of iSGS (range: 1 to 5 procedures). Patients undergoing a total of two (2) total procedures within the data collection window demonstrated a statistically significant decrease in mean stenosis length between the first and second procedures (p = 0.014). Changes in distance of the stenosis from the glottis was not found to be statistically significant (p = 0.833). There was a statistically significant decrease in mean length of stenosis from the 1st to the 2nd procedure by approximately 0.11 cm (p = 0.0003). No additional statistically significant differences in stenosis length or location were detected. Conclusions: Serial endoscopic excision/dilation procedures (the mainstay of iSGS surgical management) do not appear to significantly lengthen intraluminal stenosis nor change the distance of the stenosis from the glottis. Level of Evidence: 4 Laryngoscope, 134:1769–1772, 2024 [ABSTRACT FROM AUTHOR]

Background. The high sensitivity of cells of Fanconi anemia (FA) patients to DNA cross-linking agents (clastogens), such as mitomycin C (MMC), was used as a screening tool in Polish children with clinical suspicion of FA. Objectives. The aim of the study was to compare chromosome fragility between 3 groups, namely non-FA, possible mosaic FA and FA patients. Materials and methods. The study included 100 children with hematological manifestations and/or congenital defects characteristic of FA, and 100 healthy controls. Blood samples obtained from participants were analyzed using an MMC-induced chromosomal breakage test. Results. Patients with clinical suspicion of FA were divided into 3 subgroups based on the MMC test results, namely FA, possible mosaic FA and non-FA. Thirteen out of 100 patients had a true FA cellular phenotype. The mean value of MMC-induced chromosome breaks/cell for FA patients was higher than for non-FA patients (6.67 ±3.92 compared to 0.23 ±0.18). In addition, the percentage of cells with spontaneous aberrations was more than 9 times higher in FA patients than in non-FA patients. Conclusions. Our results confirmed that the MMC sensitivity test distinguishes between individuals affected by FA, those with possible somatic mosaicism, and patients with bone marrow failure for other reasons, who were classified as non-FA in the first diagnostic step. However, a definitive differential diagnosis requires follow-up mutation testing and chromosome breakage analysis of skin fibroblasts. [ABSTRACT FROM AUTHOR]

Background: The treatment of choice for most esophageal strictures is esophageal dilatation but it has a low success rate. This study was conducted to determine the effect of topical mitomycin C as an adjunct to dilatation therapy in esophageal strictures among children. Methods: This randomized controlled trial was conducted at the Department of Pediatric Gastroenterology, The Children’s Hospital and Institute of Child Health, Multan, Pakistan, from July 2022 to October 2023. Children aged 1-12 years and having esophageal strictures were included. A simple random sampling technique was adopted. Children in the Mitomycin C group received topical mitomycin C (2 mg/20 ml saline) during the endoscopy, whereas the placebo group received normal saline. The counts of dilatation sessions necessary in each group and the proportion of patients who were symptom-free after 12 months of therapy were noted (outcome). IBM-SPSS 26 was used for data analysis with p

AIM: To compare the success rate and complications of adjuvant use of mitomycin C and triamcinolone- impregnated biodegradable nasal packing (TABP) in endoscopic dacryocystorhinostomy (DCR). And to evaluate the efficacy of combining intraoperative mitomycin C and TABP for endoscopic DCR. METHODS: A total of 198 eyes of 148 patients who underwent endoscopic DCR for acquired nasolacrimal duct obstruction were retrospectively analysed. The patients were randomly divided into three groups: Group A included patients treated without intraoperative mitomycin C but with TABP, Group B included patients treated without triamcinolone but with intraoperative mitomycin C and normal saline-impregnated nasal packing, and Group C included patients treated with intraoperative mitomycin C and TABP. RESULTS: The results revealed no significant difference in the overall success rates between Groups A (86.8%) and B (89.2%; P=0.377). However, Group C (97.5%) showed a significantly higher overall success rate than Groups A and B. The incidence of granulomas was significantly lower in group C (5%) than in Groups A (20.8%) and B (15.2%; P=0.009). Other complications, such as crust, synechiae, and revision surgery, did not differ significantly among the three groups. CONCLUSION: The combination of intraoperative mitomycin C and TABP effectively prevents granulomas and enhances surgical success rate. Additionally, there is no statistically significant difference observed between the use of mitomycin C or TABP alone.

Filtration surgery is one of the most frequently performed surgeries in the management of glaucoma, and trabeculectomy is considered the gold standard surgical technique for the same. Though trabeculectomy has been reported to have an excellent initial success rate, about 30% of them fail in 3 years, and nearly 50% of them fail in 5 years. The most significant risk of failure still seems to be wound scarring, especially episcleral fibrosis, leading to bleb failure. As a result, it is essential to explore the role of anti-scarring agents, including mitomycin C, and 5-fluorouracil in wound modulation and improving the bleb survival rate. Since these agents are widely used in trabeculectomy, it is crucial to understand the various modes of application, advantages, and adverse effects of these agents. On an evidence-based approach, all these points have been highlighted in this review article. In addition, the newer agents available for wound modulation and their scope for practical application are discussed.

Purpose: To compare the safety and efficacy of subconjunctival injection (MMC: 0.02%) to those with subconjunctival application of sponges soaked in Mitomycin C (MMC: 0.02%) intra-operatively in patients who underwent phacotrabeculectomy. Methods: A total of 68 patients undergoing phacotrabeculectomy were randomized into two groups; the sponge group received 0.02% MMC-soaked sponges (n = 38), and the injection group received subconjunctival injection of 0.02% MMC (n = 30). The primary outcome was post-operative mean intra-ocular pressure reduction (IOP). The secondary outcomes were bleb morphology using Indiana Bleb Appearance Grading Score (IBAGS) and anterior segment optical coherence tomography (AS-OCT), post-operative use of 5-fluorouracil, and complications rates. These were compared at 1 week and 1, 3, and 6 months post-operatively. Complete success was defined as ≥30% reduction in IOP without anti-glaucoma medications. Results: In sponge and injection groups, the mean pre-operative IOP was 29.1 ± 8.1 and 29.8 ± 8.8 mmHg, respectively. At 6 months, IOP in sponge and injection groups reduced by 52% (14 ± 3.6 mmHg, P < 0.001) and 50% (15.2 ± 4.1 mmHg, P < 0.001), respectively. Complete success was observed in 90.9% in the sponge group and 95.83% in the injection group. Both groups had diffuse, shallow, relatively avascular blebs at 6 months using IBAGS and AS-OCT. A few complications were seen in the sponge group during this period, which were not vision-threatening. Conclusion: Subconjunctival MMC injection is an effective, safe, convenient, and time-saving alternative to sponge-soaked delivery of MMC in phacotrabeculectomy.

Purpose: Conjunctival melanoma with large corneal involvement is a rarity. We here present a case of conjunctival melanoma with pronounced central corneal involvement. Observation: A 69-year-old fair white male presented with a visual axis impeding corneal nodular lesion with associated conjunctival melanosis. Tumor excision with intraoperative mitomycin c (0.02 %) application for 180 seconds and amniotic membrane transplantation for defect coverage was performed in retrobulbar anesthesia. Histopathological evaluation revealed the nodular lesion to be a conjunctival melanoma (pT1a) with associated conjunctival melanocytic intraepithelial lesion (C-MIL). Conclusion and importance: Most conjunctival melanomas with corneal affection reach a radial corneal involvement of 1 mm. The here reported case accounted for 4 mm, which is seldom and therefore an important report. Surgical excision followed by intraoperative and postoperative mitomycin c exposure was a successful primary treatment. Currently there are no signs of tumor relapse in any part of the eye or the organism 12 months after excision. However, the long-term follow-up needs to be awaited.

Objective: Mitomycin C (MMC), a DNA-damaging chemotherapeutic, is commonly used clinically for recurrent cervical carcinoma (CC), either alone or in combination. MMC generates DNA damage resulting in CC cell death yet also induces increased AKT-BAD phosphorylation associated with drug resistance and reduced clinical benefit. The present study evaluates the efficacy of combined MMC and a BAD phosphorylation inhibitor in CC. Methods: The association and function of phosphorylation of BAD on serine 99 (pBADS99) for cell survival of both MMC-resistant or sensitive-CC cells was explored. BAD was mutated to BADS99A to examine the requirement of BADS99 for CC cell survival and a novel small-molecule inhibitor of pBADS99 was utilized. Cell proliferation, survival, foci formation, and patient-derived organoids (PDOs) assays were utilized to determine efficacy, synergy and related mechanisms. Results: MMC IC50 was positively correlated to the cell line pBADS99/BAD ratio. Increased BADS99 phosphorylation was observed in both MMC-sensitive or -resistant CC cells after MMC treatment. Inhibition of pBADS99 in CC cell lines produced synergistic apoptosis through BAD-mediated apoptotic pathways and enhanced DNA damage in response to MMC. The concurrent use of pharmacological inhibition of pBADS99 and MMC was synergistic, resulting in diminished cell viability and inducing apoptotic cell death in MMC-sensitive and -resistant CC cell lines or patient-derived organoids. Conclusion: A combination of MMC with inhibition of BAD phosphorylation potentiated efficacy compared to single agent treatment. The potential further development of such strategies may provide outcome benefits to patients with CC.

Background: To evaluate the safety and efficacy of the Minimally Invasive Micro Sclerotomy (MIMS) procedure in the management of uncontrolled open-angle glaucoma. Methods: A prospective, open-label, single-arm clinical evaluation with intra-subject comparisons performed at the Ophthalmologic Center after S.V. Malayan, Yerevan, Armenia. Included were adults with primary open-angle glaucoma (OAG) (N = 114) or exfoliative glaucoma (N = 6) who were uncontrolled (IOP > 21) on tolerated topical medication. Mild (N = 7), moderate (N = 66) and severe (n = 47) cases were prospectively included without preselection. Following subconjunctival Mitomycin C, an ab-interno MIMS procedure was performed alone (N = 100) or combined with phacoemulsification (N = 20). Patients were followed for 52 weeks. Procedure-related complications and adverse events were recorded. Success criteria were defined as -5 < IOP ≤ 21mmHg OR a reduction in IOP of ≥ 20% from baseline with (qualified success) or without (complete success) hypotensive medications. Results: Mean patient age was 69 ± 10.1 years. The mean duration of the procedure was 2:01 ± 0:41 min:sec. Scleral drainage channels were achieved in all cases. No device malfunctions, intraoperative complications, or serious adverse events were reported. Iris plugging of the sclerostomy site and early spikes in IOP were the most common adverse events. The only reason for failure was final IOP > 21 mmHg on tolerated medication. At 52 weeks (n = 93), mean IOP decreased by 38% from baseline (P < 0.001), from 27.9 ± 3.7 to 17.5 ± 5.3 mmHg, a difference of 10.5 mmHg (95% CI: -11.7, -9.3). One-year qualified success was documented in 82.1% (95% CI: 72.9%,89.2%) of the patients and complete success, in 70.5% (60.3-79.4%). 60% (95 CI:49.4%,69.9%) of the patients achieved maximum IOP level of 14 mmHg or at least 30% reduction in IOP. Conclusions: MIMS procedure is a relatively simple, short and safe minimally invasive bleb-forming procedure. Its efficacy, as found in this short-term evaluation, lends it suitable for mild and moderate uncontrolled open-angle glaucoma patients. Trial registration: ClinicalTrials.gov ID: NCT04503590 2019-05-29. [ABSTRACT FROM AUTHOR]

Background: The aim was to evaluate the long-term outcome and efficacy of primary trabeculectomy with adjunctive mitomycin c (MMC) for treating glaucoma. Methods: We examined the medical records of 286 eyes that underwent trabeculectomy between 2008 and 2009 at the University Eye Hospital in Freiburg, Germany. Preoperative and follow-up data were collected, including intraocular pressure (IOP) measurements, surgical glaucoma interventions, and prescribed glaucoma medication. The first success criterion was defined as IOP ≤ 15 mmHg with no use of pressure-lowering medication by the patient, the second criterion was defined as the absence of surgical revision, and the third criterion as no further IOP-lowering surgery excluding early revisions following trabeculectomy. Statistical analyses comprised Cox regression and Kaplan–Meier survival estimations. Results: The mean follow-up duration was 1841 days (5 years). The mean preoperative IOP was 26.1 mmHg. Evaluating the success criteria at the time of average follow-up yielded a success rate of only 25% for the first criterion but 80% for both the second and third success criteria. Conclusions: The findings suggest that trabeculectomy with adjunctive MMC can be an effective procedure for permanently lowering IOP. However, surgical revisions and/or further glaucoma surgeries might still be needed. The long-term success rate is lower in comparison to previous research, which may be explained by the stricter success criteria in our study. [ABSTRACT FROM AUTHOR]

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Purpose: To compare the safety and efficacy of two different application methods of mitomycin C (MMC)-soaked sponge in trabeculectomy. Study design: Retrospective study. Methods: We included 71 eyes of 71 patients that had undergone trabeculectomy. In the anterior scleral application group, 36 eyes were treated using the long side of the MMC-soaked sponge placed parallel to the limbus. The efficacy and safety in these eyes were compared with eyes treated with the posterior scleral application group, consisting of 35 eyes treated with the long side of the MMC-soaked sponge placed perpendicular to the limbus. The follow-up period was 2 years. The safety of the procedure, including bleb morphology and complications, was the primary outcome, while the success rate was the secondary outcome. Results: The cumulative success rate at 2 years postoperatively was 94.4% in the anterior and and 94.3% in the posterior scleral application group (P = 1.000). However, with the posterior scleral application of the MMC-soaked sponge, blebs were more low-lying (P = 0.048), less in extent (P < 0.001), more normally vascularized (P = 0.027) and more posteriorly directed (P < 0.001). Furthermore, the incidence of thin-walled cystic bleb (P = 0.028) and bleb leakage (P = 0.025) was significantly lower in the posterior scleral application group than in the anterior group. Conclusion: Although there were similar success rates, the posterior scleral application of MMC-soaked sponge with trabeculectomy was safer with a better bleb morphology than the anterior scleral application. [ABSTRACT FROM AUTHOR]