Desulfovibrio alaskensis is a Gram-negative bacterial species that belongs to the group of Sulphate Reducing Bacteria (SRB) and presents prophages in genomes, a common characteristic of the genus ...Desulfovibrio. Genetic material can be transported by outer membrane vesicles, however, no data regarding the production of these vesicles has been reported for D. alaskensis. To verify the expression of D. alaskensis prophages and their involvement with outer membrane vesicles, the DSM16109 strain was used. The DSM16109 strain had three prophages and presented reduced growth after mitomycin C addition when compared to the control culture. This reduction was accompanied by the presence of virus-like particles (VLPs), indicating mitomycin C dependent prophage induction. The increase in the number of cap gene copies and transcriptions of the three prophages was verified in the control sample, however, without the formation of VLPs. Prophage genes were identified in outer membrane vesicles from cultures treated and not treated with mitomycin C. DSM16109 prophages are expressed spontaneously but only in the presence of mitomycin C was it possible to observe VLP formation. Due to the genetic material detection from the prophages within outer membrane vesicles, this property may be related to the horizontal transfer of viral genes.
•Prophages genes are expressed spontaneously in Desulfovibrio alaskensis DSM 16109.•Mitomycin C reduces some prophage genes expression and induces others.•Capsids are formed without genome and tail.•Prophage genes are present inside of the outer membrane vesicles.
Compare outcomes of tube shunt surgery (Tube) and trabeculectomy with mitomycin C (Trab-MMC) in patients with angle-closure glaucoma (ACG).
Retrospective nonrandomized comparative study.
A total of ...80 eyes from 80 patients with ACG who underwent either Tube (N = 50) or Trab-MMC (N = 30) between January 2015 and January 2022 at Massachusetts Eye and Ear.
Reviewed and analyzed 390 visits from patient charts.
Kaplan-Meier (KM) success rates, intraocular pressure (IOP), medication burden, best-corrected visual acuity (BCVA), adjusted hazard ratios (HRs), and complications.
Baseline demographics were similar between both groups, except for a higher proportion of patients with pseudophakia and prior incisional ocular surgery in the Tube group. The Trab-MMC procedure had significantly higher KM complete success (CS) rates than the Tube procedure, but similar qualified success (QS) rates. Under QS, the cumulative probability of survival was 87% in the Tube group and 83% in the Trab-MMC group at year 1 (P = 0.77), and 75% in the Tube group and 58% in the Trab-MMC group at year 2 (P = 0.14). Under CS, the cumulative probability of survival was 13% in the Tube group and 59% in the Trab-MMC group at year 1 (P < 0.001), and 11% in the Tube group and 41% in the Trab-MMC group at year 2 (P < 0.001). Both Tube and Trab-MMC procedures resulted in significant patterns of IOP and medication reduction from baseline up to 2 years with mean IOP reduced to 12.6 ± 5.9 mmHg on 2.8 ± 1.4 medications after Tube and 12.1 ± 6.6 mmHg on 2.4 ± 1.7 medications after Trab-MMC. Patients who underwent Trab-MMC required less IOP-lowering medications at every follow-up visit up to year 1, but a similar number at year 2. No significant differences were found in IOP reduction, BCVA, or complication rates between groups.
We demonstrate that Trab-MMC confers similar IOP reduction and QS rates to Tube placement in patients with ACG. Trab-MMC, however, demonstrated greater medication burden reduction up to 1 year, and more favorable CS rates up to 2 years, while still maintaining similar complication rates to Tube.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
After a long period of little change, glaucoma surgery has experienced a dramatic rise in the number of possible procedures in the last two decades. Glaucoma filtering surgeries with mitomycin C and ...glaucoma drainage devices remain the standard of surgical care. Other newer surgeries, some of which are minimally or microinvasive glaucoma surgeries, target existing trabecular outflow, enhance suprachoroidal outflow, create subconjunctival blebs, or reduce aqueous production. Some require the implantation of a device such as the iStent, Hydrus, Ex‐PRESS, XEN and PRESERFLO, whilst others do not—Trabectome, Kahook dual blade, Ab interno canaloplasty, gonioscopy‐assisted transluminal trabeculotomy, OMNI and excimer laser trabeculotomy. Others are a less destructive variation of an established procedure, such as micropulse transscleral cyclophotocoagulation, endoscopic cyclophotocoagulation and ultrasound cycloplasty. Cataract surgery alone can be a significant glaucoma operation. These older and newer glaucoma surgeries, their mechanism of action, efficacy and complications are the subject of this review.
Purpose
To evaluate the efficacy and safety of using Mitomycin-C (MMC) or Ologen implant as an adjunct to combined trabeculotomy–trabeculectomy (CTT) surgery relative to non-augmented CTT surgery in ...achieving higher success rates in patients with primary congenital glaucoma (PCG).
Study design
A prospective triple-armed randomized controlled clinical trial was conducted in the period between April 2019 and May 2021, targeting 75 eyes of patients with PCG over one year, with patients being followed up for at least one whole year.
Patients and methods
The study included 75 eyes; only 70 fulfilled the inclusion criteria and were randomly assigned to one of the three study groups using a computer program to generate random number list. Eyes were treated by either CTT without augmentation, CTT augmented with MMC, or CTT augmented with Ologen implant. Only 63 eyes completed one year of follow-up and were evenly distributed among the three study groups; with 21 eyes in each group were statistically analyzed.
Outcome measures
Our primary outcome measure is to report and compare the percentage of patients who demonstrated complete success with intraocular pressure (IOP) controlled and maintained below 21 mmHg without the use of antiglaucoma medications or additional glaucoma surgery over a one-year follow-up. Secondary outcome measures include reporting failure, intra- and postoperative complications of the three surgical modalities, postoperative corneal diameter, clearance of corneal edema, and postoperative cup/disk (
C
/
D
) ratio.
Results
Complete success was achieved in 17 eyes (81.0%) in CTT group, 18 eyes (85.7%) in MMC group, and 17 eyes (81.0%) in Ologen group. Qualified success (IOP < 21 with or without antiglaucoma medications) was achieved in 18 eyes (85.7%) in both the CTT and the Ologen groups, with 19 eyes (90.5%) in the MMC group. Failure was observed in three eyes (14.3%) in both CTT and Ologen groups and two eyes (9.5%) in the MMC group. Based on survival analysis, CTT group had a cumulative success probability of 95.2% at three months, which dropped to 85.7% at six months and remained at that level for the 9th and 12th months of follow-up. With respect to the MMC group, the cumulative success probability at three months was 95.2%, dropped to 90.5% at six months, and remained at that level for the 9th and 12th months of follow-up. While in the Ologen group, the cumulative success probability at three months was 85.7% and remained at the same level during the 6th, 9th, and 12th months of follow-up, with
p
value = 0.862 using the logrank test.
Conclusion
CTT is a safe and effective primary surgical intervention in patients with PCG without the need for augmentation while preserving the augmented procedure's use for recurrent cases.
There is no effective intravesical second-line therapy for non–muscle-invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails.
To compare disease-free survival time (DFS) between ...radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/maintenance BCG.
Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 (HYMN ClinicalTrials.gov: NCT01094964).
Patients were randomly assigned (1:1) to RITE (60min, 40mg mitomycin-C, 42±2°C) or control following stratification for carcinoma in situ (CIS) status (present/absent), therapy history (failure of previous induction/maintenance BCG), and treatment centre.
Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS at randomisation subgroup. Analysis was based on intention-to-treat.
A total of 104 patients were randomised (48 RITE: 56 control). Median follow-up for the 31 patients without a DFS event was 36 mo. There was no significant difference in DFS between treatment arms (hazard ratio HR 1.33, 95% confidence interval CI 0.84–2.10, p=0.23) or in 3-mo CR rate in CIS patients (n=71; RITE: 30% vs control: 47%, p=0.15). There was no significant difference in DFS between treatment arms in non-CIS patients (n=33; RITE: 53% vs control: 24% at 24 mo, HR 0.50, 95% CI 0.22–1.17, p=0.11). DFS was significantly lower in RITE than in control in CIS with/without papillary patients (n=71; HR 2.06, 95% CI 1.17–3.62, p=0.01; treatment-subgroup interaction p=0.007). Disease progression was observed in four patients in each treatment arm. Adverse events and health-related quality of life between treatment arms were comparable.
DFS was similar between RITE and control. RITE may be a second-line therapy for non-CIS recurrence following BCG failure; however, confirmatory trials are needed. RITE patients with CIS with/without papillary had lower DFS than control. HYMN highlights the importance of the control arm when evaluating novel therapies.
This study did not show a difference in bladder cancer outcomes between microwave-heated chemotherapy and standard of care treatment. Papillary bladder lesions may benefit from microwave-heated chemotherapy treatment; however, more research is needed. Both treatments are similarly well tolerated.
Radiofrequency-induced thermo-chemotherapy effect (RITE) had similar oncological outcomes as control. RITE-treated noncarcinoma in situ (CIS) patients reported nonsignificant better disease-free survival (DFS). RITE-treated CIS with/without papillary patients had significantly lower DFS. Control arm is essential when evaluating novel therapies.
Mitomycin C (MC) is a well‐known DNA alkylating agent. MC analog, 10‐decarbamoyl mitomycin C (DMC), unlike MC, has stronger effects on cancer with p53 mutation. We previously demonstrated that MC/DMC ...could activate p21WAF1/CIP1 in MCF‐7 (p53‐proficient) and K562 (p53‐deficient) cells in a p53‐independent mode. This study aimed to elucidate the upstream signaling pathway of p21WAF1/CIP1 activation triggered by MC/DMC. Besides p53, Akt plays an important role on deactivating p21WAF1/CIP1. The results showed that MC/DMC inhibited Akt in MCF‐7 cells, but not in K562 cells. By knocking down p53, the Akt inhibition in MCF‐7 cells was alleviated. This implied that the deactivated Akt caused by MC/DMC was p53‐dependent. With Akt activator (SC79), p21WAF1/CIP1 activation triggered by MC/DMC in MCF‐7 cells was not reduced. This indicated that Akt inhibition triggered by MC/DMC was not associated with MC/DMC‐induced p21WAF1/CIP1 activation. Label‐free quantitative proteomic profiling analysis revealed that DMC has a stronger effect on down‐regulating the PI3K/Akt signaling pathway in MCF‐7 cells as compared to MC. No significant effect of MC/DMC on PI3K/Akt in K562 cells was observed. In summary, MC/DMC regulate Akt activation in a p53‐dependent manner. This Akt deactivation is not associated with p21WAF1/CIP1 activation in response to MC/DMC.
Deactivation of AKT was observed in MCF‐7 cells treated with mitomycin C (MC) and its analog 10‐decarbamoyl mitomycin C (DMC) in a p53‐dependent manner. However, deactivation of Akt did not associate with p21 activation in response to MC and DMC in MCF‐7 cells. Proteomic profiling analysis showed that DMC has a stronger effect on down‐regulation of Akt protein expression in MCF‐7 cells as compared to MC, while there is no effect of MC/DMC on Akt signaling pathway in K562 cells.
Purpose: Patients with glaucoma undergoing trabeculectomy develop bleb cicatrix causing poor postoperative intraocular pressure (IOP) control and low success rates. Several approaches have been ...explored over the years for better outcomes. This study assesses the safety, efficacy, and outcome of trabeculectomy with HealaFlow® (Anteis S. A, Geneva, Switzerland), a high-molecular-weight cross-linked hyaluronic acid viscoelastic gel, and comparing it with the antimetabolite Mitomycin-C (MMC). Methods: A prospective, interventional, case-controlled study conducted at a tertiary care hospital in Southern India on 60 eyes of patients requiring trabeculectomy divided in two groups - HealaFlow scleral implant and adjuvant low-dose MMC (0.1 mg/mL). Postoperative IOP reduction along with bleb morphology was assessed over follow-up at 1 week, 1 month, 3 months, 6 months, and 12 months. Results: Preoperatively IOP in the two groups was statistically similar. Postoperative IOP on day 1 had statistically significant reduction in both groups with greater reduction in MMC group. However, by 12 months, the IOP reduction was statistically similar in both groups, i.e., 46.24% (to 11.04 ± 2.55 mmHg) and 54.47% (to 11.99 ± 3.37 mmHg) in HealaFlow® group and MMC group, respectively (P > 0.05). The bleb morphologies were similar and complications were seen equally, which resolved by 4 weeks. A complete success rate of 89.29% and a qualified success rate of 10.71% were observed equally in both groups. Conclusion: Absorbable biosynthetic cross-linked hyaluronic acid and low-dose MMC are equally safe and efficacious in trabeculectomy with significant IOP reduction and good bleb morphology. Therefore, it is a novel substitute for MMC.
The efficacy of an immediate single chemotherapy instillation after transurethral resection of a bladder tumour (TURBT) in patients with non–muscle-invasive bladder cancer (NMIBC) remains a topic of ...debate. Evidence is even more scarce when an immediate instillation is followed by adjuvant instillations.
To compare the effect of a mitomycin C (MMC) instillation within 24h to an instillation 2 wk after TURBT in patients with NMIBC with or without adjuvant instillations.
Between 1998 and 2003, 2844 NMIBC patients were randomised for immediate versus delayed MMC instillation after TURBT. Patients were categorised in low-risk (LOR), intermediate-risk (IMR), and high-risk (HIR) groups. Total numbers of instillations in these groups were 1, 9, and 15, respectively.
Primary end point was 3-yr recurrence risk for the IMR and HIR groups and 5-yr risk for the LOR group. Secondary outcomes were time to recurrence and incidence of adverse events. Analyses were performed with the log-rank test, Cox-regression, and χ2 test in SPSS.
A total of 2243 patients were eligible on an intention-to-treat basis. Recurrence risks were 43% and 46% in the LOR group (5-yr follow-up, p=0.11), 20% and 32% in the IMR group (3-yr follow-up, p=0.037), and 28% and 35% in the HIR group (3-yr follow-up, p=0.007), for an immediate and a delayed instillation, respectively. For all patients, the recurrence risk was 27% (95% confidence interval CI, 24–30) in the immediate and 36% (95% CI, 33–39) in the delayed instillation group (p<0.001) with a 27% reduction in relative recurrence risk (hazard ratio: 0.73, 95% CI, 0.63–0.85, p<0.001). The incidence of adverse events did not differ significantly between treatment groups (immediate instillation 25%, delayed instillation 22%, p=0.08). The risk groups in our study differ slightly from the current guidelines, which is a limitation of our study.
An immediate, single instillation after TURBT reduces the recurrence risk in NMIBC patients, independent of the number of adjuvant installations.
A single instillation of chemotherapy after the resection of non–muscle-invasive bladder cancer reduces the recurrence risk, even if patients are treated with an adjuvant schedule of instillations.
An intravesical instillation with mitomycin C within 24h after transurethral resection of a bladder tumour reduces the risk of recurrence in non–muscle-invasive bladder cancer patients, independent of the number of adjuvant installations.
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