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Introduction. Patients with non-ST elevation acute coronary syndromes (NSTE-ACS) are sometimes severely hemodynamicly compromised. Urgent coronary angiography should be performed in these patients in percutaneous coronary intervention (PCI) centers according to the ESC NSTE-ACS guidelines to determine suitabilty for percutaneous or surgical revascularization. Case report. We reported a 62-year-old male with chest pain admitted to the Coronary Care Unit. ST segment depression of 2 mm in leads I, L and V4-6 was revealed at electrocardiogram. After following 6 hours the patient had chest pain and signs of cardiogenic shock despite of the therapy. Chest x-ray showed pulmonary edema. Echocardiographic examination showed dyskinetic medium and apical segments of septum. The patient underwent coronary angiography immediately which revealed 75% stenosis of the left main coronary artery with thrombus. The use of a GPIIb/III inhibitor-tirofiban and stent implantation resulted in TIMI III flow. After that the patient had no chest pain and acute heart failure subsided in the following days Echocardiography done at the fourth day from PCI showed only hypokinesis medium and apical segment of septum. The patient was discharged at day 11 from admission in a stable condition. Conclusion. Stenting of left main coronary artery stenosis in patients with cardiogenic shock and non- ST segment elevation acute coronary syndromes may be a life saving procedure.

Aaron Spitz,1 Marc Gittelman,2 Lawrence I Karsh,3 Sanja Dragnic,4 Ahmed M Soliman,5 Aditya Lele,6 Damian Gruca,7 Michael Norton4 1Orange County Urology Associates, Laguna Beach, CA, 221st Century Oncology/UroMedix-Aventura Division, Aventura, FL, 3The Urology Center of Colorado, Denver, CO, 4US Medical Affairs, 5Health Economics and Outcomes Research, 6Data and Statistical Sciences, AbbVie Inc., North Chicago, IL, USA; 7Global Medical Affairs, AbbVie Deutschland, Ludwigshafen, Germany Introduction: Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to “castrate” levels, historically defined as

The presence of persulfate (S 2 O 8 ) in decontamination processes favors the oxidation of organic pollutants due to its strong oxidation power. In this research we study the photoelectrochemical generation of persulfate using five mixed metal oxides electrodes (MMO) with different compositions and its effect on the degradation of sulfamethoxazole antibiotic (SMX) by photoelectrocatalysis (PEC) and electro-oxidation (EO). By PEC, all anodes generated a higher concentration of S 2- ) in decontamination processes favors the oxidation of organic pollutants due to its strong oxidation power. In this research we study the photoelectrochemical generation of persulfate using five mixed metal oxides electrodes (MMO) with different compositions and its effect on the degradation of sulfamethoxazole antibiotic (SMX) by photoelectrocatalysis (PEC) and electro-oxidation (EO). By PEC, all anodes generated a higher concentration of S 2 than those not exposed to light. The high S 8 2- than those not exposed to light. The high S 2 O 8 2- concentration obtained by PEC was 0.150 mM using MMO [Ti/Ir/Ta] in a solution with Na 2 SO 4 100 mM applying a current density of 2 mA/cm 2 . On the other hand, the maximum concentration obtained was 0.250 mM at 30 min of electrolysis for MMO [Ti/Ir/Ta] . S 2 SO 4 50 mM and applying current density of 5 mA/cm 2 . S 2 showed the best S 8 2- production. The effect of S 2 O 5 electro-generation (using the anode with the highest and the anode with the lowest S 2 O 8 2- production. The effect of S 2 O 8 2- By EO, the degradation of SMX was partial, demonstrating that the electrophotocatalytic effect favors the generation of S 2 O 8 2- production) on the degradation of sulfamethoxazole by PEC and EO was studied using the experimental conditions with the best production of this oxidant. MMO [Ti/Ir/Ta] and MMO [Ti/Ru] were used as anodes, and it was observed that by PEC, 100% of SMX was degraded after 30 min of electrolysis using MMO [Ti/Ir/Ta] and 60 min using MMO [Ti/Ru]. By EO, the degradation of SMX was partial, demonstrating that the electrophotocatalytic effect favors the generation of S 2 O 8 2- , enhancing the degradation of SMX at short electrolysis times., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Context: Treatment options for central precocious puberty (CPP) are important for individualization of therapy., Objective: We evaluated the efficacy and safety of 6-month 45-mg leuprolide acetate (LA) depot with intramuscular administration., Methods: LA depot was administered at weeks 0 and 24 to treatment-naïve (n = 27) or previously treated (n = 18) children with CPP in a phase 3, multicenter, single-arm, open-label study (NCT03695237). Week 24 peak-stimulated luteinizing hormone (LH) suppression (<4 mIU/mL) was the primary outcome. Secondary/other outcomes included basal sex hormone suppression (girls, estradiol <20 pg/mL; boys, testosterone <30 ng/dL), suppression of physical signs, height velocity, bone age, patient/parent-reported outcomes, and adverse events., Results: All patients (age, 7.8 ± 1.27 years) received both scheduled study doses. At 24 weeks, 39/45 patients (86.7%) had LH suppressed. Six were counted as unsuppressed; 2 because of missing data, 3 with LH of 4.35-5.30 mIU/mL and 1 with LH of 21.07 mIU/mL. Through 48 weeks, LH, estradiol, and testosterone suppression was achieved in ≥86.7%, ≥97.4%, and 100%, respectively (as early as week 4 for LH and estradiol and week 12 for testosterone). Physical signs were suppressed at week 48 (girls, 90.2%; boys, 75.0%). Mean height velocity ranged 5.0 to 5.3 cm/year post-baseline in previously treated patients and declined from 10.1 to 6.5 cm/year at week 20 in treatment-naïve patients. Mean bone age advanced slower than chronological age. Patient/parent-reported outcomes remained stable. No new safety signals were identified. No adverse event led to treatment discontinuation., Conclusion: Six-month intramuscular LA depot demonstrated 48-week efficacy with a safety profile consistent with other GnRH agonist formulations., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Objectives: It is important to understand what variables influence change in predicted adult height (PAH) throughout GnRHa treatment for central precocious puberty (CPP) to individualize treatment decisions and optimize care., Methods: Changes in PAH, chronological age (CA), bone age (BA), BA/CA, and height velocity (HV) were evaluated in girls with CPP throughout treatment with leuprolide acetate (n=77). A second analysis focused on changes in the 3 years preceding the first observed BA of ≥12 years. Relationships were characterized using plot inspection and linear mixed-effects analyses. Association between treatment duration and last assessed PAH was examined using multiple linear regression models., Results: BA/CA and HV showed a nonlinear change during treatment, with the largest changes and improvement in PAH observed in the first 6-18 months. Rate of BA advancement tended to decrease more slowly in girls initiating treatment at a younger BA. On-treatment change in PAH was predicted by concurrent BA/CA change, HV, and BA, as well as CA at treatment initiation. Last assessed PAH was positively associated with longer treatment durations (primary/exploratory models cut-offs of ≥33/≥55 months)., Conclusions: These findings support individualized monitoring during GnRHa treatment. Initial response should be interpreted with caution until 6-18 months after treatment initiation and failure should not be assumed based on continued bone maturation in girls starting therapy at a younger age. Treatment cessation should not be automatically based on a diminishing change in PAH or HV, as ongoing treatment may result in continued increase or maintenance of PAH., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: Gonadotropin-releasing hormone agonist treatment is important for optimal growth in girls with central precocious puberty (CPP). Data are lacking regarding benefit to height outcome when treatment is started after chronological age (CA) of 7 years, and if continued beyond CA of 10 years or bone age (BA) of 12 years., Methods: Forty-eight girls with CPP were treated with monthly leuprolide depot. Change in predicted adult height (PAH) during treatment was assessed. Changes in PAH and growth velocity were compared between girls initiating treatment at CA <7 vs. ≥7 years, and BA ≥12 vs. BA <12 years., Results: Mean baseline CA was 6.8 years, BA, 10.2 years; and PAH, 156.4 cm. BA/CA ratio decreased from pretreatment values, averaging 1.5 to 1.2 at the end of treatment. Proportion of girls with >5 cm PAH change during treatment was similar, and PAH increased throughout treatment in most girls, regardless of age at treatment initiation. PAH continued to increase in 16/19 girls who continued treatment after BA of 12 years, and also in 16/22 girls who continued treatment after CA of 10 years., Conclusions: PAH improved in most girls who initiated treatment after CA of 7 years. It continued to improve in most girls with longer treatment, even past BA of 12 years or CA of 10 years, which suggests that no absolute CA or BA limit should define initiation or end of treatment. Treatment plans need to be individualized, and neither treatment initiation nor cessation should be based on BA or CA alone., (© 2021 Marcela Vargas Trujillo et al., published by De Gruyter, Berlin/Boston.)

A rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics and reducing the therapeutic arsenal available for treatment of infectious diseases. In the present study, we developed a new class of compounds with antibacterial activity obtained by a simple, two step synthesis and screened the products for in vitro antibacterial activity against ATCC ® strains using the broth microdilution method. The compounds exhibited minimum inhibitory concentrations (MIC) of 1⁻32 μg/mL against Gram-positive ATCC ® strains. The structure⁻activity relationship indicated that the thiophenol ring is essential for antibacterial activity and the substituents on the thiophenol ring module, for antibacterial activity. The most promising compounds detected by screening were tested against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) clinical isolates. We found remarkable activity against VREF for compounds 7 and 16 , were the MIC 50/90 were 2/4 µg/mL and 4/4 µg/mL, respectively, while for vancomycin the MIC 50/90 was 256/512 µg/mL. Neither compound affected cell viability in any of the mammalian cell lines at any of the concentrations tested. These in vitro data show that compounds 7 and 16 have an interesting potential to be developed as new antibacterial drugs against infections caused by VREF.

Background: Children with central precocious puberty (CPP) are treated with gonadotropin-releasing hormone agonists (GnRHa) to suppress puberty. Optimizing treatment outcomes continues to be studied. The relationships between growth, rate of bone maturation (bone age/chronological age [ΔBA/ΔCA]), luteinizing hormone (LH), predicted adult stature (PAS), as well as variables influencing these outcomes, were studied in children treated with depot leuprolide (LA Depot) Methods: Subjects (64 girls, seven boys) with CPP received LA Depot every 3 months for up to 42 months. Multivariate regression analyses were conducted to examine the predictors affecting ΔBA/ΔCA, PAS and growth rate., Results: Ninety percent of subjects (18 of 20) were suppressed (LH levels <4 IU/L) at 42 months. Over 42 months, the mean growth rate declined 2 cm/year, the mean BA/CA ratio decreased 0.21 and PAS increased 8.90 cm for girls (n=64). PAS improved to mid-parental height (MPH) in 46.2% of children by 30 months of treatment. Regression analysis showed that only the Body Mass Index Standardized Score (BMI SDS) was significantly associated (β+0.378 and +0.367, p≤0.05) with growth rate. For PAS, significant correlations were with MPH (β+0.808 and +0.791, p<0.001) and ΔBA/ΔCA (β+0.808 and +0.791, p<0.001). For ΔBA/ΔCA, a significant association was found only with BA at onset of treatment (β-0.098 and -0.103, p≤0.05). Peak-stimulated or basal LH showed no significant influence on growth rate, ΔBA/ΔCA or PAS., Conclusions: Growth rate and bone maturation rate normalized on treatment with LA Depot. LH levels were not significantly correlated with growth rate, ΔBA/ΔCA or PAS, suggesting that suppression was adequate and variations in gonadotropin levels were below the threshold affecting outcomes.

1. Isradipine and lacidipine, two new drugs that are members of the nitro-aryl-1,4-dihydropyridine family, produced inhibition of both growth cultures and oxygen consumption on epimastigotes of Trypanosoma cruzi Tulahuen strain, at micromolar concentrations. 2. Isradipine was found to be the most potent derivative in both, in growth cultures (I50 = 20.8 microM) and in vivo oxygen uptake (I50 = 31.1 microM). 3. Diltiazem and verapamil, two well-known calcium channel antagonists, lacked inhibitory activity, even at a 100 microM concentration. 4. The present findings indicate that the trypanocide effects exerted by isradipine and lacidipine are not related with a disruption of the calcium homeostasis of the parasite.

A series of nitro aryl 1,4-dihydropyridine derivatives produced inhibition of both cell growth and oxygen consumption on Tulahuen and LQ strains, and clone Dm 28c of epimastigotes of Trypanosoma cruzi. Nicardipine was found to be the most potent derivative in both growth cell (I50 = 70 microM) and oxygen uptake (I50 = 26 microM in intact parasites, I50 = 325 microM in situ mitochondria). A correlation between the inhibitory effects on the growth cell and the apparent first order kinetic for the uptake of the 1,4-dihypyridine derivatives by T. cruzi epimastigotes was found. Thus, nicardipine, the most potent derivative, exhibited the highest apparent rate constant, ku, (0.043 min-1). On the other hand, no susceptibility differences by strains and clone Dm 28c to the action of these drugs were found.