Jasmonate-insensitive mutant jar1b prevents petal elongation and flower opening coupling with parthenocarpic fruit development in Cucurbita pepo.

Jasmonates are growth regulators that play a key role in flower development, fruit ripening, root growth, and plant defence. The study explores the coordination of floral organ maturation to ensure proper flower opening for pollination and fertilization. A new mutant (jar1b) was discovered, lacking petal elongation and flower opening but showing normal pistil and stamen development, leading to parthenocarpic fruit development. The mutation also enhanced the elongation of roots while reducing the formation of root hairs. BSA sequencing showed that jar1b is a missense mutation in the gene CpJAR1B, which encodes the enzyme that catalyzes the conjugation between JA and the amino acid isoleucine. The loss of function mutation in CpJAR1B produced a deficiency in biologically active (+) -7-iso-jasmonoyl-L-isoleucine (JA-Ile), which was not complemented by the paralogous gene CpJAR1A or any other redundant gene. Exogenous application of methyl jasmonate (MeJA) demonstrated that jar1b is partially insensitive to JA in both flowers and roots. Further experimentation involving the combination of JA-Ile deficient and ethylene-deficient, and ET insensitive mutations in double mutants revealed that CpJAR1B mediated ET action in female petal maturation and flower opening, but JA and ET have independent additive effects as negative regulators of the set and development of squash fruits. CpJAR1B also regulated the aperture of male flowers in an ethylene-independent manner. The root phenotype of jar1b and effects of external MeJA treatments indicated that CpJAR1B has a dual role in root development, inhibiting the elongation of primary and secondary roots, but promoting the formation of root hairs.

Production and characterization of the lipopeptide with anti-adhesion for oral biofilm on the surface of titanium for dental implants.

Titanium implants are subject to bacterial adhesion and peri-implantitis induction, and biosurfactants bring a new alternative to the fight against infections. This work aimed to produce and characterize the biosurfactant from Bacillus subtilis ATCC 19,659, its anti-adhesion and antimicrobial activity, and cell viability. Anti-adhesion studies were carried out against Streptococcus sanguinis, Staphylococcus aureus, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Proteus mirabilis as the minimum inhibitory concentration and the minimum bactericidal concentration. Cell viability was measured against osteoblast and fibroblast cells. The biosurfactant was classified as lipopeptide, with critical micelle concentration at 40 µg mL- 1, and made the titanium surface less hydrophobic. The anti-adhesion effect was observed for Staphylococcus aureus and Streptococcus sanguinis with 54% growth inhibition and presented a minimum inhibitory concentration of 15.7 µg mL- 1 for Streptococcus sanguinis and Aggregatibacter actinomycetemcomitans. The lipopeptide had no cytotoxic effect and demonstrated high potential application against bacterial biofilms.

The transcription factor CpMYB62 controls the genetic network that leads to the determination of female flowers in Cucurbita pepo.

In monoecious species, female flowering constitutes the developmental process that determines the onset and production of fruit and is therefore closely related to crop yield. This article presents the identification and phenotypic and molecular characterization of myb62, an ethylmethane sulfonate loss-of-function mutation that completely blocks the female floral transition, converting all female flowers into male flowers. BSA-seq analysis coupled with WGS showed that myb62 corresponds to a C>T transition in the coding region of the gene CpMYB62, generating a premature stop codon and a truncated transcription factor without its N-terminal effector domain. The myb62 phenotype was partially rescued by exogenous ethylene application, indicating that the function of CpMYB62 is mediated by ethylene. Different evidence supports this conclusion: first, the reduced ethylene production of the mutant, and second, the male flower productive phenotype of the double mutant between myb62 and the ethylene-insensitive mutant etr2b, which demonstrated that myb62 is epistatic over etr2b. Furthermore, transcriptomic analysis of WT and myb62 apical shoots confirmed that CpMYB62 regulates master sex-determining genes, upregulating those encoding the ethylene biosynthesis enzymes CpACO2B and CpACS27A and those encoding for transcription factors that promote the development of carpels(CpCRC), but downregulating those involved in the arrest of carpels (CpWIP1), In the gene network controlling sex determination in cucurbits, CpMYB62 occupies the most upstream position, activating ethylene and other sex determining genes involved in female flower determination in Cucurbita  pepo.

Giant Midline Prostatic Cyst: An Unusual Cause of Acute Urinary Retention.

Midline prostatic cysts are infrequent and mostly asymptomatic. We presented a striking case of a giant midline cyst and detailed its diagnosis, evolution, and treatment. From this case, we offered a comparison of congenital intraprostatic midline cysts, namely, Müller's cysts and utricle cysts. A 40-year-old male experienced recurrent urinary retention. A 10 × 11 mm2 cyst in the mid-prostatic region was diagnosed through transrectal ultrasound, leading to a transperineal puncture as a minimally invasive intervention. Seven years later, the cyst recurred, manifesting obstructive symptoms such as a weak urinary stream, frequent urination, and residual urine sensation. Laparoscopic surgery was then performed for the confirmed 98 × 13 mm2 cystic recurrence. The postoperative course was favourable with no complications. Symptoms were completely resolved, which was maintained over a three-year follow-up period. The therapeutic approach to midline cysts targets symptomatic cases or infertility, ranging from cyst puncture to transurethral endoscopic treatment. Recurrence after minimally invasive interventions is a challenge, with laparoscopic surgery as an alternative post-failed conservative approach. Although total cyst removal risks adjacent structure damage, marsupialisation improves the clinical outcomes. In summary, symptomatic midline prostatic cysts present challenges owing to recurrences after minimally invasive approaches. Enhanced laparoscopic techniques offer a solution, particularly in highly symptomatic cases requiring definitive treatment, as illustrated by this outstanding case report.

Structural and functional characterization of genes PYL-PP2C-SnRK2s in the ABA signalling pathway of Cucurbita pepo.

BACKGROUND: The core regulation of the abscisic acid (ABA) signalling pathway comprises the multigenic families PYL, PP2C, and SnRK2. In this work, we conducted a genome-wide study of the components of these families in Cucurbita pepo. RESULTS: The bioinformatic analysis of the C. pepo genome resulted in the identification of 19 CpPYL, 102 CpPP2C and 10 CpSnRK2 genes. The investigation of gene structure and protein motifs allowed to define 4 PYL, 13 PP2C and 3 SnRK2 subfamilies. RNA-seq analysis was used to determine the expression of these gene families in different plant organs, as well as to detect their differential gene expression during germination, and in response to ABA and cold stress in leaves. The specific tissue expression of some gene members indicated the relevant role of some ABA signalling genes in plant development. Moreover, their differential expression under ABA treatment or cold stress revealed those ABA signalling genes that responded to ABA, and those that were up- or down-regulated in response to cold stress. A reduced number of genes responded to both treatments. Specific PYL-PP2C-SnRK2 genes that had potential roles in germination were also detected, including those regulated early during the imbibition phase, those regulated later during the embryo extension and radicle emergence phase, and those induced or repressed during the whole germination process. CONCLUSIONS: The outcomes of this research open new research lines for agriculture and for assessing gene function in future studies.

Venoarterial extracorporeal membrane oxygenation for vasoplegic shock after treprostinil refill of an implanted intravenous pump: a case report.

Introduction: Venoarterial extracorporeal membrane oxygenation (ECMO) is a rescue therapy that can stabilize patients with hemodynamic compromise. Indications continue to evolve, including drug overdose. However, the indication merely for vasoplegic shock following drug overdose is controversial. Case summary: We report a case of a 57-year-old male with high-risk idiopathic pulmonary arterial hypertension treated with upfront triple combination therapy (sildenafil, bosentan, and intravenous treprostinil infusion via subcutaneous abdominal implantable pump). In one of the refills of the drug reservoir, accidental administration of 1 months's supply of treprostinil (200 mg) into the subcutaneous tissue occurred, causing refractory vasoplegic shock. He required urgent VA-ECMO for 96 h, surviving to discharge 28 days later. Discussion: Treprostinil poisoning is rare due to its less frequent use but is life-threatening. ECMO may be considered in vasoplegic shock due to overdose of vasodilatory medication. It allows organ perfusion to be maintained, with the knowledge that recovery is as rapid as drug elimination.

Mitochondrial and ribosomal markers in the identification of nematodes of clinical and veterinary importance.

BACKGROUND: Nematodes of the Ascarididae, Ancylostomatidae and Onchocercidae families are parasites of human and veterinary importance causing infections with high prevalence worldwide. Molecular tools have significantly improved the diagnosis of these helminthiases, but the selection of genetic markers for PCR or metabarcoding purposes is often challenging because of the resolution these may show. METHODS: Nuclear 18S rRNA, internal transcribed spacers 1 (ITS-1) and 2 (ITS-2), mitochondrial gene cytochrome oxidase 1 (cox1) and mitochondrial rRNA genes 12S and 16S loci were studied for 30 species of the mentioned families. Accordingly, their phylogenetic interspecies resolution, pairwise nucleotide p-distances and sequence availability in GenBank were analyzed. RESULTS: The 18S rRNA showed the least interspecies resolution since separate species of the Ascaris, Mansonella, Toxocara or Ancylostoma genus were intermixed in phylogenetic trees as opposed to the ITS-1, ITS-2, cox1, 12S and 16S loci. Moreover, pairwise nucleotide p-distances were significantly different in the 18S compared to the other loci, with an average of 99.1 ± 0.1%, 99.8 ± 0.1% and 98.8 ± 0.9% for the Ascarididae, Ancylostomatidae and Onchocercidae families, respectively. However, ITS-1 and ITS-2 average pairwise nucleotide p-distances in the three families ranged from 72.7% to 87.3%, and the cox1, 12S and 16S ranged from 86.4% to 90.4%. Additionally, 2491 cox1 sequences were retrieved from the 30 analyzed species in GenBank, whereas 212, 1082, 994, 428 and 143 sequences could be obtained from the 18S, ITS-1, ITS-2, 12S and 16S markers, respectively. CONCLUSIONS: The use of the cox1 gene is recommended because of the high interspecies resolution and the large number of sequences available in databases. Importantly, confirmation of the identity of an unknown specimen should always be complemented with the careful morphological examination of worms and the analysis of other markers used for specific parasitic groups.

An miR164-resistant mutation in the transcription factor gene CpCUC2B enhances carpel arrest and ectopic boundary specification in Cucurbita pepo flower development.

The sex determination process in cucurbits involves the control of stamen or carpel development during the specification of male or female flowers from a bisexual floral meristem, a function coordinated by ethylene. A gain-of-function mutation in the miR164-binding site of CpCUC2B, ortholog of the Arabidopsis transcription factor gene CUC2, not only produced ectopic floral meristems and organs, but also suppressed the development of carpels and promoted the development of stamens. The cuc2b mutation induced the transcription of CpCUC2B in the apical shoots of plants after female flowering but repressed other CUC genes regulated by miR164, suggesting a conserved functional redundancy of these genes in the development of squash flowers. The synergistic androecious phenotype of the double mutant between cuc2b and etr2b, an ethylene-insensitive mutation that enhances the production of male flowers, demonstrated that CpCUC2B arrests the development of carpels independently of ethylene and CpWIP1B. The transcriptional regulation of CpCUC1, CpCUC2, and ethylene genes in cuc2b and ethylene mutants also confirms this conclusion. However, the epistasis of cuc2b over aco1a, a mutation that suppresses stamen arrest in female flowers, and the down-regulation of CpACS27A in cuc2b female apical shoots, indicated that CpCUC2B promotes stamen development by suppressing the late ethylene production.

Comparative RNA-Seq Analysis between Monoecious and Androecious Plants Reveals Regulatory Mechanisms Controlling Female Flowering in Cucurbita pepo.

In the monoecious Cucurbita pepo, the transition to female flowering is the time at which the plant starts the production of female flowers after an initial male phase of development. Ethylene plays an essential role in this process since some ethylene deficient and ethylene-insensitive mutants are androecious and only produce male flowers. To gain insight into the molecular mechanisms regulating the specification and early development of female flowers, we have compared the transcriptomic changes occurring in the shoot apices of WT and androecious ethylene-insensitive etr1b mutant plants upon female flowering transition. There were 1160 female flowering-specific DEGs identified in WT plants upon female flowering, and 284 of them were found to be modulated by the ethylene-insensitive etr1b mutation. The function of these DEGs indicated that female flower specification depends on the adoption of a transcriptional program that includes previously identified sex-determining genes in the ethylene pathway, but also genes controlling the biosynthesis and signaling pathways of other phytohormones, and those encoding for many different transcription factors. The transcriptomic changes suggested that gibberellins play a negative role in female flowering, while ethylene, auxins, ABA and cytokinins are positive regulators. Transcription factors from 34 families, including NAC, ERF, bHLH, bZIP, MYB and C2H2/CH3, were found to be regulating female flowering in an ethylene-dependent or -independent manner. Our data open a new perspective of the molecular mechanisms that control the specification and development of female flowers in C. pepo.

Readiness for Change in the Implementation of a 3D Printing Initiative in a Catalan Tertiary Hospital Using the Normalization Process Theory: Survey Study.

BACKGROUND: The high failure rate of innovation projects motivates us to understand the perceptions about resistances and barriers of the main stakeholders to improving success rates. OBJECTIVE: This study aims to analyze the readiness for change in the implementation of a 3D printing project in a Catalan tertiary hospital prior to its implementation. METHODS: We used a web-based, voluntary, and anonymous survey using the Normalization Measurement Development questionnaire (NoMAD) to gather views and perceptions from a selected group of health care professionals at Germans Trias i Pujol University Hospital. RESULTS: In this study, 58 professionals, including heads of service (n=30, 51%), doctors (n=18, 31%), nurses (n=7, 12%), and support staff (n=3, 5%), responded to the questionnaire. All groups saw the value of the project and were willing to enroll and support it. Respondents reported the highest scores (out of 5) in cognitive participation (mean 4.45, SD 0.04), coherence (mean 3.72, SD 0.13), and reflective monitoring (mean 3.80, SD 0.25). The weakest score was in collective action (mean 3.52, SD 0.12). There were no statistically significant differences in scores among professions in the survey. CONCLUSIONS: The 3D printing project implementation should pay attention to preparing, defining, sharing, and supporting the operational work involved in its use and implementation. It should also understand, assess, and communicate the ways in which the new set of practices can affect the users and others around them. We suggest that health officers and politicians consider this experience as a solid ground toward the development of a more efficient health innovation system and as a catalyst for transformation.

ATM/Chk2 and ATR/Chk1 Pathways Respond to DNA Damage Induced by Movento® 240SC and Envidor® 240SC Keto-Enol Insecticides in the Germarium of Drosophila melanogaster.

DNA damage response (DDR) pathways in keto-enol genotoxicity have not been characterized, and few studies have reported genotoxic effects in non-target organisms. The present study shows that concentrations of 11.2, 22.4, 37.3 mg/L of Movento® 240SC and 12.3, 24.6, 41.1 mg/L of Envidor® 240SC for 72 h oral exposure induced DSBs by significantly increasing the percentage of γH2AV expression in regions 2b and 3 from the germarium of wild type females of Drosophila melanogaster Oregon R, compared to the control group (0.0 mg/L of insecticides), via confocal immunofluorescence microscopy. The comparison between both insecticides' reveals that only the Envidor® 240SC induces concentration-dependent DNA damage, as well as structural changes in the germarium. We determined that the DDR induced by Movento® 240SC depends on the activation of the ATMtefu, Chk1grp and Chk2lok kinases by significantly increasing the percentage of expression of γH2AV in regions 2b and 3 of the germarium, and that ATRmei-29D and p53dp53 kinases only respond at the highest concentration of 37.3 mg/L of Movento® 240SC. With the Envidor® 240SC insecticide, we determined that the DDR depends on the activation of the ATRmei-29D/Chk1grp and ATMtefu/Chk2lok kinases, and p53dp53 by significantly increasing the percentage of expression of γH2AV in the germarium.

Results of fusion prostate biopsy comparing with cognitive and systematic biopsy.

PURPOSE: Our study aims to determine whether there are differences in the degree of detection of prostate cancer (PCa) and CsPCa between fusion prostate biopsy (FPB), cognitive biopsy (PCB), and randomized, systematic biopsy (SB). METHODS: A retrospective analysis was carried out of 195 patients with suspected PCa at the San Cecilio University Clinical Hospital in Granada who underwent a prostate biopsy between January and December 2021. Patients were divided into three groups: group 1, patients undergoing FPB transperineally with ultrasound BK 3000 (N = 87); group 2, PCB (N = 59) transperineally; and group 3, transrectal SB (N = 49), the latter two, with an ultrasound BK Specto. RESULTS: We found differences in favor of image-directed biopsies (FPB and PCB) with a percentage of positive biopsies of 52.8% and 50%, respectively, compared to 41.4% with SB, but without these differences being significant. Given the controversy in performing prostate biopsies in PI-RADS 3 lesions reported in the literature, a subanalysis was performed excluding the FPB performed for PI-RADS 3 lesions (PI-RADS 4 and 5 are included), finding significant differences when comparing FPB with PCB and SB (group 1, 64% vs group 2, 45.8%; p = 0.05) (group 1, 64% vs group 3, 42.9%; p = 0.035). CONCLUSION: With the results obtained in our series, we conclude that the finding of a PI-RADS 3 lesion in mpMRI should not be an absolute criterion to indicate prostate biopsy. On the other hand, for PI-RADS 4 and 5 lesions, FPB is recommended, which in this case turns out to be superior to PCB and SB.

Preoperative parathyroid localization. Relevance of MIBI SPECT-CT in adverse scenarios.

PURPOSE: Selective parathyroidectomy, the treatment of choice for primary hyperparathyroidism, requires precise preoperative localization. Our purpose was to compare the accuracy and concordance of pre-surgical MIBI parathyroid scintigraphy and ultrasonography, as well as to assess the relevance of hybrid acquisition (SPECT/CT) in compromised circumstances: low-weight or ectopic adenomas, coexisting thyroid disease and re-interventions. METHODS: The study included 223 patients with primary hyperparathyroidism operated in a single Surgical Unit from August 2016 to March 2021. Preoperative ultrasonography and double-phase MIBI were performed with early SPECT/CT acquisition. A minimally invasive surgical approach was initially attempted, except in patients with concomitant thyroid surgery or multiglandular parathyroid disease. RESULTS: Selective parathyroidectomy was accomplished in 179 patients (80.2%); cervicotomy and/or thoracoscopy in 44. Removal of the parathyroid lesion was achieved in 211 patients (94.6%), corresponding 204 (96.7%) to adenomas (37 ectopic). The cure rate was 94.2%. Preoperative MIBI SPECT/CT showed higher sensitivity and accuracy (84%; 80%) compared to ultrasound (72%; 71%), being more precise in defining the exact anatomical location (75.8% vs 68.7%). These differences reached statistical significance in ectopic glands. The existence of concomitant thyroid pathology did not decrease the sensitivity of SPECT/CT (84.2%). Mean parathyroid weight was 692.2mg (95%CI: 443.5-941) in MIBI-negative cases and 1145.9mg (95%CI: 983.6-1308.3) in MIBI-positive (p=0.001). Re-intervention was successful in the 8 patients with previous surgery. CONCLUSION: MIBI SPECT/CT presents greater sensitivity, accuracy and anatomical precision than ultrasound for preoperative parathyroid localization, even in the case of ectopic glands or coexisting thyroid pathology. The weight of the pathological gland is a significantly limiting factor.

The Alarm Fatigue Challenge in the Neonatal Intensive Care Unit: A "before" and "after" Study.

OBJECTIVE: Alarm fatigue (AF) happens when professionals are exposed to many alarms and they become desensitized to them. It is related to proliferation of devices, not standardized alarm limits, and high prevalence of "nonactionable alarms," i.e., false alarms (triggered by equipment issues) or nuisance alarms (physiological change not requiring clinical action). When AF happens, response time seems to be longer and important alarms could be dismissed. After evaluating the situation in our neonatal intensive care unit (NICU), an alarm management program (AMP) was developed to reduce AF. The objective of this study were to compare the proportion of true alarms, nonactionable alarms, and to measure response time to alarms in the NICU before and after implementing an AMP and also to determine variables associated with nonactionable alarms and response time. STUDY DESIGN: This was a cross-sectional study. A total of 100 observations were collected between December 2019 and January 2020. After an AMP was implemented, 100 new observations were collected between June 2021 and August 2021. We estimated the true and nonactionable alarms proportion. Univariate analyses were performed to determine variables associated with nonactionable alarms and response time. Logistic regression was performed to assess independent variables. RESULTS: The proportion of true alarms before and after AMP was 31 versus 57% (p = 0.001), whereas the proportion of nonactionable alarms was 69 versus 43% (p = 0.001). Median response time was significantly reduced (35 versus 12 seconds; p = 0.001). Before AMP, neonates with less intensive care needs had a higher proportion of nonactionable alarms and a longer response time. After AMP, response time was similar for true and nonactionable alarms. For both periods, the need of respiratory support was significantly associated with true alarms (p = 0.001). In the adjusted analysis, response time (p = 0.001) and respiratory support (p = 0.003) remained associated with nonactionable alarms. CONCLUSION: AF was highly prevalent in our NICU. This study shows that after the implementation of an AMP, response time to alarms and the proportion of nonactionable alarms can be significantly reduced. KEY POINTS: · AF happens when professionals are exposed to many alarms and they become desensitized to them.. · The presence of AF can compromise patients' safety.. · The implementation of an AMP can reduce AF..

How to Design Successful Participatory Design Workshops for Digital Health Solutions?

Participatory design (PD) is increasingly used to support design and development of digital health solutions. The involves representatives of future user groups and experts to collect their needs and preferences and ensure easy to use and useful solutions. However, reflections and experiences with PD in designing digital health solutions are rarely reported. The objective of this paper is to collect those experiences including lessons learnt and moderator experiences, and to identify challenges. For this purpose, we conducted a multiple case study to explore the skill development process required to successfully design a solution in the three cases. From the results, we derived good practice guidelines to support designing successful PD workshops. They include adapting the workshop activities and material to the vulnerable participant group and considering their environment and previous experiences, planning sufficient time for preparation and supporting the activities with appropriate material. We conclude that PD workshop results are perceived as useful for designing digital health solutions, but careful design is very relevant.

Increases in group A streptococcal infections in the pediatric population in Houston, TX, 2022.

Beginning in October 2022, we observed a substantial increase in the total number of cases of invasive GAS disease (iGAS) in the pediatric population in Houston, TX. Emm12 GAS strains were disproportionately represented but the overall proportion of iGAS infections observed during the current spike was similar to pre-pandemic years.

An engineered HIV-1 Gag-based VLP displaying high antigen density induces strong antibody-dependent functional immune responses.

Antigen display on the surface of Virus-Like Particles (VLPs) improves immunogenicity compared to soluble proteins. We hypothesised that immune responses can be further improved by increasing the antigen density on the surface of VLPs. In this work, we report an HIV-1 Gag-based VLP platform engineered to maximise the presence of antigen on the VLP surface. An HIV-1 gp41-derived protein (Min), including the C-terminal part of gp41 and the transmembrane domain, was fused to HIV-1 Gag. This resulted in high-density MinGag-VLPs. These VLPs demonstrated to be highly immunogenic in animal models using either a homologous (VLP) or heterologous (DNA/VLP) vaccination regimen, with the latter yielding 10-fold higher anti-Gag and anti-Min antibody titres. Despite these strong humoral responses, immunisation with MinGag-VLPs did not induce neutralising antibodies. Nevertheless, antibodies were predominantly of an IgG2b/IgG2c profile and could efficiently bind CD16-2. Furthermore, we demonstrated that MinGag-VLP vaccination could mediate a functional effect and halt the progression of a Min-expressing tumour cell line in an in vivo mouse model.

Digital transformation in organizational health and safety to mitigate Burnout Syndrome.

In 2000, the World Health Organization (WHO) identified Burnout Syndrome as an occupational risk factor, affecting an estimated 10% of workers, resulting in lost productivity and increased costs due to sick leave. Some claim that Burnout Syndrome has reached epidemic proportions in workplaces around the world. While signs of burnout are not difficult to identify and palliate, its real impact is not easy to measure, generating a number of risks for companies from possible loss of human talent to decreased productivity and diminished quality of life. Given the complexity of Burnout Syndrome, it must be addressed in a creative, innovative and systematic way; traditional approaches cannot be expected to deliver different results. This paper describes the experience where an innovation challenge was launched to collect creative ideas to identify, prevent or mitigate Burnout Syndrome through the use of technological tools and software. The challenge was endowed with an economic award and its guidelines stated that the proposals must be both creative and feasible from an economic and organizational point of view. A total of twelve creative projects were submitted, including each of them, the analysis, design and management plans, to envision an idea that is feasible and with the appropriate budget, implemented. In this paper, we present a summary of these creative projects and how the IRSST (Instituto Regional de Seguridad y Salud en el Trabajo) experts and leaders in OHS in the Madrid Region (Spain) envision their potential impact on improving the OHS landscape.

Adjuvant intravesical treatment in patients with intermediate and high-risk non-muscle-invasive bladder cancer with BCG versus MMC applied with COMBAT or EMDA. Results of a prospective study.

BACKGROUND: Bacillus Calmette-Guerin (BCG) maintenance therapy is the standard adjuvant treatment of high- and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). However, the problems of shortages and the adverse effects, both local and systemic, that it causes lead to the search for alternatives with devices that improve the penetration of intravesical chemotherapeutics. MATERIALS AND METHODS: Prospective observational study was conducted from August 2018 to August 2022. Patients diagnosed with intermediate and high-risk NMIBC without CIS who received one of the following three treatments were included: BCG in induction protocol with six weekly instillations and maintenance with three weekly instillations at months 3, 6, and 12. MMC was applied by Physionizer® 30 device with a current of 20 mA for 30 min was used in an induction protocol of 6 weekly instillations followed by 6 monthly instillations as maintenance (EMDA group). MMC was applied by COMBAT BRS System V2.0 device at 43 ± 0.5 â„ƒ for 60 min was used in an induction protocol of 6 weekly instillations followed by 6 monthly instillations as maintenance (HIVEC group). The primary objective was to compare the 24-month recurrence-free rate between the three groups. The secondary objectives were to evaluate the rate free of progression at 24 months and the degree of toxicity of the treatments. RESULTS: One hundred and eighty-three patients divided into a HIVEC group with sixty-one patients, EMDA group with fifty-nine patients, and BCG group with sixty-three patients. After a mean follow-up of 25 months (IQR 13-36), the 24-month recurrence-free rate was 82.1% for HIVEC, 80% for EMDA, and 84.6% for BCG (p > 0.05), and a progression-free rate at 24 months of 95.6% for HIVEC, 98.3% for EMDA, and 92.9% for BCG (p > 0.05). No statistically significant differences were found between the three groups with respect to the degree of reported adverse events. CONCLUSION: Adjuvant treatment with BCG or MMC applied with COMBAT or EMDA does not present differences in the recurrence-free rate and progression at 24 months in our population of patients with intermediate- and high-risk NMBC without CIS.