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International Journal of Ophthalmology 2024
PubMed: 38895670
DOI: 10.18240/ijo.2024.06.25 -
Journal of Clinical Medicine May 2024The purpose of this study is to investigate outcomes of visual acuity (VA) and intraocular pressure (IOP) in proliferative diabetic retinopathy (PDR)-associated...
The purpose of this study is to investigate outcomes of visual acuity (VA) and intraocular pressure (IOP) in proliferative diabetic retinopathy (PDR)-associated neovascular glaucoma (NVG) in Japanese patients treated with surgical therapies without the use of glaucoma drainage devices. A retrospective analysis of medical records was conducted for 31 consecutive PDR-associated NVG patients who underwent surgical treatments in our institution between 2013 and 2022. Patient demographics, clinical characteristics, VA, and IOP were recorded at the first and last visits, and surgical procedures, including pars plana vitrectomy with extensive panretinal and ciliary photocoagulation (PPV-PRCP), diode laser trans-scleral cyclophotocoagulation (DCPC), and trabeculectomy with mitomycin C (TLE-MMC), with or without a prior intravitreal bevacizumab (IVB) injection, were reviewed. Of the thirty-one PDR patients with NVG, two patients received PPV-PRCP or DCPC alone (6.5%), respectively, three patients received TLE-MMC alone (9.7%), two patients received TLE-MMC after IVB (6.5%), six patients received PPV-PRCP and TLE-MMC (19.4%), seven patients received PPV-PRCP and TLE-MMC after IVB (22.6%), five patients received PPV-PRCP and DCPC and TLE-MMC (16.1%), and four patients received PPV-PRCP and DCPC and TLE-MMC after IVB (12.9%). The VA of two patients (6.5%) deteriorated to no light perception. In all patients, the mean logMAR VA was 1.28 ± 1.05 at the first visit and remained at 1.26 ± 1.08 at the last visit, with no significant change; the mean IOP was 33.0 ± 15.2 mmHg at the initial visit and decreased significantly to 14.0 ± 7.4 mmHg at the last visit. The number of eyes with IOP ≥ 21 decreased from twenty-eight (90.3%) to three (9.7%). Although IOP in patients with IOP > 30 mmHg at the initial visit reduced to a level comparable to that of patients with IOP ≤ 30 mmHg, the IOP > 30 mmHg group received IVB more frequently and had significantly higher logMAR VA at the last visit compared to the IOP ≤ 30 mmHg group. Hypotony (<6 mmHg) was observed in four eyes (12.9%). In PDR patients with NVG, various combinations of PPV-PRCP, DCPC, and TLE-MMC after adjunctive IVB without the use of glaucoma drainage devices lowered IOP sufficiently; for these patients, neovascular regression was observed, with no further deterioration of VA. However, surgical procedures should be performed for PDR patients with NVG before visual impairment occurs. On the other hand, approximately less than 15% of patients developed blindness or low IOP.
PubMed: 38892963
DOI: 10.3390/jcm13113252 -
Frontiers in Oncology 2024Mitomycin-C (MMC) chemotherapy is a well-established anti-cancer treatment for non-muscle-invasive bladder cancer (NMIBC). However, despite comprehensive biological...
Mitomycin-C (MMC) chemotherapy is a well-established anti-cancer treatment for non-muscle-invasive bladder cancer (NMIBC). However, despite comprehensive biological research, the complete mechanism of action and an ideal regimen of MMC have not been elucidated. In this study, we present a theoretical investigation of NMIBC growth and its treatment by continuous administration of MMC chemotherapy. Using temporal ordinary differential equations (ODEs) to describe cell populations and drug molecules, we formulated the first mathematical model of tumor-immune interactions in the treatment of MMC for NMIBC, based on biological sources. Several hypothetical scenarios for NMIBC under the assumption that tumor size correlates with cell count are presented, depicting the evolution of tumors classified as small, medium, and large. These scenarios align qualitatively with clinical observations of lower recurrence rates for tumor size ≤ 30[mm] with MMC treatment, demonstrating that cure appears up to a theoretical [mm] tumor size threshold, given specific parameters within a feasible biological range. The unique use of mole units allows to introduce a new method for theoretical pre-treatment assessments by determining MMC drug doses required for a cure. In this way, our approach provides initial steps toward personalized MMC chemotherapy for NMIBC patients, offering the possibility of new insights and potentially holding the key to unlocking some of its mysteries.
PubMed: 38884094
DOI: 10.3389/fonc.2024.1352065 -
Graefe's Archive For Clinical and... Jun 2024To evaluate the effect of postoperative interferon-alpha 2b (IFN-α2b) ophthalmic drops versus intraoperative mitomycin-c (MMC) on preventing pterygium recurrence.
PURPOSE
To evaluate the effect of postoperative interferon-alpha 2b (IFN-α2b) ophthalmic drops versus intraoperative mitomycin-c (MMC) on preventing pterygium recurrence.
METHODS
This prospective randomized clinical trial was conducted on patients who were candidates for pterygium surgery. A total of 75 patients were included in the study from December 2021 to December 2022, of which 64 patients (one eye each) were examined and analyzed based on the inclusion criteria. Then the patients were randomly assigned to control groups, intra-operative MMC (32 patients) and the intervention group, IFN-α2b drops after the operation (32 patients). All patients underwent pterygium surgery using the rotational conjunctival flap method.
RESULTS
In terms of pterygium grading, 8 (12.5%), 25 (39.06%), and 31 (48.44%) eyes were in grades 1, 2, and 3, respectively. The average size of the pterygium was 3.6 ± 0.7 mm. The grade and size of pterygium had the same distribution in the two groups. There was no statistically significant difference between the two groups in the level of post-operative clinical inflammation. The present study showed no significant difference in complications between the two groups (p = 0.999). The recurrence rate in the control group was 9.4% (3 eyes), and 0% (no recurrence) in the intervention group (p = 0.119).
CONCLUSIONS
interferon-alpha 2b group did not show a statistically significant difference in preventing pterygium recurrence compared to the mitomycin C group. The post-surgery administration of IFN-α 2b drops can effectively prevent pterygium recurrence with a comparable and even more compelling effect than MMC during surgery.
PubMed: 38878067
DOI: 10.1007/s00417-024-06548-0 -
Journal of Paediatrics and Child Health Jun 2024Stricture formation is the most common remote complication of caustic ingestion. The aim of this study was evaluation of the efficacy of early topical endoscopic...
AIM
Stricture formation is the most common remote complication of caustic ingestion. The aim of this study was evaluation of the efficacy of early topical endoscopic application of mitomycin C (MMC) in prevention of stricture formation after corrosive ingestion in children.
METHODS
We enrolled 78 children with a history of caustic ingestion within 48 h in a prospective, randomised-controlled study. Only 61 children completed the study and were classified into two groups: group A and B. After initial stabilisation, patients in group A (n = 30) received topical application of MMC within the initial 48 h while patients in group B (n = 31) only received conventional management. Follow-up endoscopic dilatation was done every 2 weeks to patients in either group until no need for further dilatation.
RESULTS
The barium study, which was done on the third week, revealed that all the patients (100%) on conservative management (group B) had strictures while only nine patients (30%) in group A had strictures (P < 0.001). The median number of dilatations required for patients in group B was 26 (min. = 23 and max. = 32) while in group A, it was 0 (min. = 0 and max. = 7) (P < 0.001). The success of early MMC application was complete response in 26 patients (86.7%), partial response in 3 patients (10%) and no response in 1 patient (3.3%). On the other side, conventional therapy with endoscopic dilatation achieved complete response in 11 patients (35.5%).
CONCLUSION
Early topical MMC application proved its efficacy and safety in prevention of scar and stricture formation in children following caustic ingestion.
PubMed: 38874187
DOI: 10.1111/jpc.16595 -
Microbial Cell Factories Jun 2024Bacterial infections and the rising antimicrobial resistance pose a significant threat to public health. Pseudomonas aeruginosa produces bacteriocins like pyocins,...
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). 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.
Topics: Pseudomonas aeruginosa; Anti-Bacterial Agents; Bacteriocins; Microbial Sensitivity Tests; Pyocins; Humans; Pseudomonas Infections
PubMed: 38872163
DOI: 10.1186/s12934-024-02450-w -
BioRxiv : the Preprint Server For... May 2024During HTLV-1 infection, the virus integrates into the host cell genome as a provirus with a single CCCTC binding protein (CTCF) binding site (vCTCF-BS), which acts as...
During HTLV-1 infection, the virus integrates into the host cell genome as a provirus with a single CCCTC binding protein (CTCF) binding site (vCTCF-BS), which acts as an insulator between transcriptionally active and inactive regions. Previous studies have shown that the vCTCF-BS is important for maintenance of chromatin structure, regulation of viral expression, and DNA and histone methylation. Here, we show that the vCTCF-BS also regulates viral infection and pathogenesis in a humanized (Hu) mouse model of adult T-cell leukemia/lymphoma. Three cell lines were used to initiate infection of the Hu-mice, i) HTLV-1-WT which carries an intact HTLV-1 provirus genome, ii) HTLV-1-CTCF, which contains a provirus with a mutated vCTCF-BS which abolishes CTCF binding, and a stop codon immediate upstream of the mutated vCTCF-BS which deletes the last 23 amino acids of p12, and iii) HTLV-1-p12stop that contains the intact vCTCF-BS, but retains the same stop codon in p12 as in the HTLV-1-CTCF cell line. Hu-mice were infected with mitomycin treated or irradiated HTLV-1 producing cell lines. There was a delay in pathogenicity when Hu-mice were infected with the CTCF virus compared to mice infected with either p12 stop or WT virus. Proviral load (PVL), spleen weights, and CD4 T cell counts were significantly lower in HTLV-1-CTCF infected mice compared to HTLV-1-p12stop infected mice. Furthermore, we found a direct correlation between the PVL in peripheral blood and death of HTLV-1-CTCF infected mice. In cell lines, we found that the vCTCF-BS regulates Tax expression in a time-dependent manner. The scRNAseq analysis of splenocytes from infected mice suggests that the vCTCF-BS plays an important role in activation and expansion of T lymphocytes . Overall, these findings indicate that the vCTCF-BS regulates Tax expression, proviral load, and HTLV pathogenicity .
PubMed: 38853836
DOI: 10.1101/2024.05.28.596170 -
Ophthalmology. Glaucoma Jun 2024To compare the effectiveness and adverse event profile of standalone SIBS microshunt implantation with adjunct MMC 0.2 mg/ml and MMC 0.4 mg/ml.
PURPOSE
To compare the effectiveness and adverse event profile of standalone SIBS microshunt implantation with adjunct MMC 0.2 mg/ml and MMC 0.4 mg/ml.
DESIGN
Mega-analysis using individual patient data from international prospective and retrospective clinical studies.
STUDY POPULATION
Patients with glaucoma who underwent implantation of a SIBS microshunt with MMC as a standalone procedure.
METHODS
A comparison of eyes that received MMC 0.2 mg/ml or 0.4 mg/ml MAIN OUTCOMES MEASURES: Primary outcome was complete success defined as the proportion of eyes at one year with all of the following: (1) no two consecutive IOPs > 17 mmHg; (2) no clinical hypotony (3) ≥20% IOP reduction from baseline and (4) no use of glaucoma medications. Secondary outcomes included IOP thresholds of 12 mmHg,14 mm Hg and 21mmHg, median IOP, number of medications, risk factors for failure, interventions, adverse events, and reoperations.
RESULTS
At 1 year, the complete success rate was significantly higher (71.3% vs 50.46%, p<0.001) and the median IOP significantly lower (13.0 vs. 14.2 mmHg, p<0.05) in the MMC 0.4 mg/ml group. MMC 0.2 mg/ml was found to be a significant risk factor for failure (HR 1.75 95%CI 1.14 to 2.67). Needling and surgical revision occurred at a lower rate in the MMC 0.4 mg/ml group (7% vs. 18.8%, p= 0.002 and 4.3% vs.13.7% p= 0.0087, respectively). Adverse events occurred at a similar frequency in both groups (26.6% MMC 0.2 mg/ml vs. 29.6% MMC 0.4 mg/ml, p=0.46), most of which were early and transient.
CONCLUSION
SIBS microshunt implantation with MMC 0.4 mg/ml resulted in a higher success rate with greater IOP reduction compared to MMC 0.2 mg/ml. Higher MMC concentration was not associated with increased serious adverse events.
PubMed: 38851392
DOI: 10.1016/j.ogla.2024.06.001 -
The Journal of Surgical Research Jun 2024Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging... (Review)
Review
INTRODUCTION
Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging functional outcomes of VCA, the consequences of long-term immunosuppression remain the main obstacle in its application. In this review, we provide researchers and surgeons with a summary of the latest advances in the field of cell-based therapies for VCA tolerance.
METHODS
Four electronic databases were searched: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature , and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as the basis of our organization.
RESULTS
Hematopoietic stem cells prolonged VCA survival. A combination of immature dendritic cells and tacrolimus was superior to tacrolimus alone. T cell Ig domain and mucin domain modified mature dendritic cells increased VCA tolerance. Bone marrow-derived mesenchymal stem cells prolonged survival of VCAs. A combination of adipose-derived mesenchymal stem cells, cytotoxic T-lymphocyte antigen 4 immunoglobulin, and antilymphocyte serum significantly improved VCA tolerance. Ex-vivo allotransplant perfusion with recipient's bone marrow-derived mesenchymal stem cells increased VCA survival. Recipient's adipose-derived mesenchymal stem cells and systemic immunosuppression prolonged VCA survival more than any of those agents alone. Additionally, a combination of peripheral blood mononuclear cells shortly incubated in mitomycin and cyclosporine significantly improved VCA survival. Finally, a combination of donor recipient chimeric cells, anti-αβ-T cell receptor (TCR), and cyclosporine significantly prolonged VCA tolerance.
CONCLUSIONS
Evidence from animal studies shows that cell-based therapies can prolong survival of VCAs. However, there remain many obstacles for these therapies, and they require rigorous clinical research given the rarity of the subjects and the complexity of the therapies. The major limitations of cell-based therapies include the need for conditioning with immunosuppressive drugs and radiation, causing significant toxicity. Safety concerns also persist as most research is on animal models. While completely replacing traditional immunosuppression with cell-based methods is unlikely soon, these therapies could reduce the need for high doses of immunosuppressants and improve VCA tolerance.
PubMed: 38851085
DOI: 10.1016/j.jss.2024.04.079 -
The Journal of Urology Jun 2024Nonmuscle-invasive bladder cancer (NMIBC) has high recurrence rates and is often treated with mitomycin C (MMC) and bacillus Calmette-Guérin (BCG). Their efficacy...
PURPOSE
Nonmuscle-invasive bladder cancer (NMIBC) has high recurrence rates and is often treated with mitomycin C (MMC) and bacillus Calmette-Guérin (BCG). Their efficacy relies on phase 2 enzyme metabolism and immune response activation, respectively. Dietary isothiocyanates, phytochemicals in cruciferous vegetables, are phase 2 enzyme inducers and immunomodulators, and may impact treatment outcomes. We investigated the modifying effects of cruciferous vegetable and isothiocyanate intake on recurrence risk following MMC or BCG treatment.
MATERIALS AND METHODS
Self-reported cruciferous vegetable intake, estimated isothiocyanate intake, and urinary isothiocyanate metabolites were collected from 1158 patients with incident NMIBC in the prospective Be-Well Study. Hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazards regression models for risk of first recurrences, and random effects Cox shared frailty models for multiple recurrences.
RESULTS
Over median follow-up of 23 months, 343 (30%) recurrences occurred. Receipt of MMC and BCG was associated with decreased risks of first recurrence (MMC: HR = 0.58; 95% CI: 0.46-0.73; BCG: HR = 0.66; 95% CI: 0.49-0.88) and multiple recurrences (MMC: HR = 0.55; 95% CI: 0.44-0.68; BCG: HR = 0.72; 95% CI: 0.55-0.95). Patients receiving BCG and having high intake (>2.4 servings/mo), but not low intake, of raw cruciferous vegetables had reduced risk of recurrence (HR: 0.56; 95% CI: 0.36-0.86; for interaction = .02) and multiple recurrences (HR: 0.51; 95% CI: 0.34-0.77; for interaction < .001). The inverse association between MMC receipt and recurrence risk was not modified.
CONCLUSIONS
For NMIBC patients who receive induction BCG, increasing consumption of raw cruciferous vegetables could be a promising strategy to attenuate recurrence risk.
PubMed: 38848543
DOI: 10.1097/JU.0000000000004070