Drug screening and development cascade for Chagas disease: an update of in vitro and in vivo experimental models.

Chagas disease is a tropical neglected disease that affects millions of people worldwide, still demanding a more effective and safer therapy, especially in its chronic phase which lacks a treatment that promotes substantial parasitological cure. The technical note of Romanha and collaborators published in 2010 aimed establish a guideline with the set of minimum criteria and decision gates for the development of new agents against Trypanosoma cruzi with the focus on developing new antichagasic drugs. In this sense, the present review aims to update this technical note, bringing the state of the art and new advances on this topic in recent years.

New 2-nitroimidazole-N-acylhydrazones, analogs of benznidazole, as anti-Trypanosoma cruzi agents.

Chagas disease is a neglected tropical parasitic disease caused by the protozoan Trypanosoma cruzi. Worldwide, an estimated 8 million people are infected with T. cruzi, causing more than 10,000 deaths per year. Currently, only two drugs, nifurtimox and benznidazole (BNZ), are approved for its treatment. However, both are ineffective during the chronic phase, show toxicity, and produce serious side effects. This work aimed to obtain and evaluate novel 2-nitroimidazole-N-acylhydrazone derivatives analogous to BNZ. The design of these compounds used the two important pharmacophoric subunits of the BNZ prototype, the 2-nitroimidazole nucleus and the benzene ring, and the bioisosterism among the amide group of BNZ and N-acylhydrazone. The 27 compounds were obtained by a three-step route in 57%-98% yields. The biological results demonstrated the potential of this new class of compounds, since eight compounds were potent and selective in the in vitro assay against T. cruzi amastigotes and trypomastigotes using a drug-susceptible strain of T. cruzi (Tulahuen) (IC50 = 4.3-6.25 µM) and proved to be highly selective with low cytotoxicity on L929 cells. The type I nitroreductase (TcNTR) assay suggests that the new compounds may act as substrates for this enzyme.

A Prototype for an Intelligent Water Management System for Household Use.

Water scarcity is becoming an issue of more significant concern with a major impact on global sustainability. For it, new measures and approaches are urgently needed. Digital technologies and tools can play an essential role in improving the effectiveness and efficiency of current water management approaches. Therefore, a solution is proposed and validated, given the limited presence of models or technological architectures in the literature to support intelligent water management systems for domestic use. It is based on a layered architecture, fully designed to meet the needs of households and to do so through the adoption of technologies such as the Internet of Things and cloud computing. By developing a prototype and using it as a use case for testing purposes, we have concluded the positive impact of using such a solution. Considering this is a first contribution to overcome the problem, some issues will be addressed in a future work, namely, data and device security and energy and traffic optimisation issues, among several others.

A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens.

The human immunodeficiency virus (HIV) produces the pathologic basis of acquired immunodeficiency syndrome (AIDS). An increase in the viral load in the body leads to a decline in the number of T lymphocytes, compromising the patient's immune system. Some opportunistic diseases may result, such as tuberculosis (TB), which is the most common in seropositive patients. Long-term treatment is required for HIV-TB coinfection, and cocktails of drugs for both diseases are used concomitantly. The most challenging aspects of treatment are the occurrence of drug interactions, overlapping toxicity, no adherence to treatment and cases of resistance. Recent approaches have involved using molecules that can act synergistically on two or more distinct targets. The development of multitarget molecules could overcome the disadvantages of the therapies used to treat HIV-TB coinfection. This report is the first review on using molecules with activities against HIV and Mycobacterium tuberculosis (MTB) for molecular hybridization and multitarget strategies. Here, we discuss the importance and development of multiple targets as a means of improving adherence to therapy in cases of the coexistence of these pathologies. In this context, several studies on the development of structural entities to treat HIV-TB simultaneously are discussed.

Anti-Trypanosoma cruzi Activity, Mutagenicity, Hepatocytotoxicity and Nitroreductase Enzyme Evaluation of 3-Nitrotriazole, 2-Nitroimidazole and Triazole Derivatives.

Chagas disease (CD), which is caused by Trypanosoma cruzi and was discovered more than 100 years ago, remains the leading cause of death from parasitic diseases in the Americas. As a curative treatment is only available for the acute phase of CD, the search for new therapeutic options is urgent. In this study, nitroazole and azole compounds were synthesized and underwent molecular modeling, anti-T. cruzi evaluations and nitroreductase enzymatic assays. The compounds were designed as possible inhibitors of ergosterol biosynthesis and/or as substrates of nitroreductase enzymes. The in vitro evaluation against T. cruzi clearly showed that nitrotriazole compounds are significantly more potent than nitroimidazoles and triazoles. When their carbonyls were reduced to hydroxyl groups, the compounds showed a significant increase in activity. In addition, these substances showed potential for action via nitroreductase activation, as the substances were metabolized at higher rates than benznidazole (BZN), a reference drug against CD. Among the compounds, 1-(2,4-difluorophenyl)-2-(3-nitro-1H-1,2,4-triazol-1-yl)ethanol (8) is the most potent and selective of the series, with an IC50 of 0.39 µM and selectivity index of 3077; compared to BZN, 8 is 4-fold more potent and 2-fold more selective. Moreover, this compound was not mutagenic at any of the concentrations evaluated, exhibited a favorable in silico ADMET profile and showed a low potential for hepatotoxicity, as evidenced by the high values of CC50 in HepG2 cells. Furthermore, compared to BZN, derivative 8 showed a higher rate of conversion by nitroreductase and was metabolized three times more quickly when both compounds were tested at a concentration of 50 µM. The results obtained by the enzymatic evaluation and molecular docking studies suggest that, as planned, nitroazole derivatives may utilize the nitroreductase metabolism pathway as their main mechanism of action against Trypanosoma cruzi. In summary, we have successfully identified and characterized new nitrotriazole analogs, demonstrating their potential as promising candidates for the development of Chagas disease drug candidates that function via nitroreductase activation, are considerably selective and show no mutagenic potential.

The Use of Zidovudine Pharmacophore in Multi-Target-Directed Ligands for AIDS Therapy.

The concept of polypharmacology embraces multiple drugs combined in a therapeutic regimen (drug combination or cocktail), fixed dose combinations (FDCs), and a single drug that binds to different targets (multi-target drug). A polypharmacology approach is widely applied in the treatment of acquired immunodeficiency syndrome (AIDS), providing life-saving therapies for millions of people living with HIV. Despite the success in viral load suppression and patient survival of combined antiretroviral therapy (cART), the development of new drugs has become imperative, owing to the emergence of resistant strains and poor adherence to cART. 3'-azido-2',3'-dideoxythymidine, also known as azidothymidine or zidovudine (AZT), is a widely applied starting scaffold in the search for new compounds, due to its good antiretroviral activity. Through the medicinal chemistry tool of molecular hybridization, AZT has been included in the structure of several compounds allowing for the development of multi-target-directed ligands (MTDLs) as antiretrovirals. This review aims to systematically explore and critically discuss AZT-based compounds as potential MTDLs for the treatment of AIDS. The review findings allowed us to conclude that: (i) AZT hybrids are still worth exploring, as they may provide highly active compounds targeting different steps of the HIV-1 replication cycle; (ii) AZT is a good starting point for the preparation of co-drugs with enhanced cell permeability.

A bibliometric analysis and visualization of e-learning adoption using VOSviewer.

Even though being perceived as a novel approach, multiple authors claim that the digital transition of all sectors in society started when information and communication technologies (ICT) started to be an integral part of our daily lives. The education sector currently represents one of the contexts where the use of ICT is more promising and allows to reach greater benefits, mostly due to the wide range of tools, applications, and management and methodological approaches that are associated with e-learning. With the above in mind, a bibliometric analysis of the e-learning adoption topic has been performed, aiming on delivering a detailed analysis of the status of the topic. This analysis was carried out by analyzing the scientific literature indexed in the Scopus database that addressed the multiple stages of the e-learning adoption process (i.e., acceptance, adoption, and use). Our study analyzed 896 documents published between 1989 and 2021, of which 98.3% represented papers published in journals and conference proceedings.

In vitro antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19.

BACKGROUND: Current approaches of drug repurposing against COVID-19 have not proven overwhelmingly successful and the SARS-CoV-2 pandemic continues to cause major global mortality. SARS-CoV-2 nsp12, its RNA polymerase, shares homology in the nucleotide uptake channel with the HCV orthologue enzyme NS5B. Besides, HCV enzyme NS5A has pleiotropic activities, such as RNA binding, that are shared with various SARS-CoV-2 proteins. Thus, anti-HCV NS5B and NS5A inhibitors, like sofosbuvir and daclatasvir, respectively, could be endowed with anti-SARS-CoV-2 activity. METHODS: SARS-CoV-2-infected Vero cells, HuH-7 cells, Calu-3 cells, neural stem cells and monocytes were used to investigate the effects of daclatasvir and sofosbuvir. In silico and cell-free based assays were performed with SARS-CoV-2 RNA and nsp12 to better comprehend the mechanism of inhibition of the investigated compounds. A physiologically based pharmacokinetic model was generated to estimate daclatasvir's dose and schedule to maximize the probability of success for COVID-19. RESULTS: Daclatasvir inhibited SARS-CoV-2 replication in Vero, HuH-7 and Calu-3 cells, with potencies of 0.8, 0.6 and 1.1 µM, respectively. Although less potent than daclatasvir, sofosbuvir alone and combined with daclatasvir inhibited replication in Calu-3 cells. Sofosbuvir and daclatasvir prevented virus-induced neuronal apoptosis and release of cytokine storm-related inflammatory mediators, respectively. Sofosbuvir inhibited RNA synthesis by chain termination and daclatasvir targeted the folding of secondary RNA structures in the SARS-CoV-2 genome. Concentrations required for partial daclatasvir in vitro activity are achieved in plasma at Cmax after administration of the approved dose to humans. CONCLUSIONS: Daclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, may be further fostered as an anti-COVID-19 therapy.

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia.

The enzyme tyrosine kinase BCR-Abl-1 is the main molecular target in the treatment of chronic myeloid leukemia and can be competitively inhibited by tyrosine kinase inhibitors such as imatinib. New potential competitive inhibitors were synthesized using the (phenylamino)pyrimidine-pyridine (PAPP) group as a pharmacophoric fragment, and these compounds were biologically evaluated. The synthesis of twelve new compounds was performed in three steps and assisted by microwave irradiation in a 1,3-dipolar cycloaddition to obtain 1,2,3-triazole derivatives substituted on carbon C-4 of the triazole nucleus. All compounds were evaluated for their inhibitory activities against a chronic myeloid leukemia cell line (K562) that expresses the enzyme tyrosine kinase BCR-Abl-1 and against healthy cells (WSS-1) to observe their selectivity. Three compounds showed promising results, with IC50 values between 1.0 and 7.3 µM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1 in the docking studies.

Phenylhydrazides as inhibitors of Leishmania amazonensis arginase and antileishmanial activity.

Searching for new substances with antileishmanial activity, we synthesized and evaluated a series of α,α-difluorohydrazide and α,α-difluoramides against Leishmania amazonensis arginase (LaArg). Four α,α-difluorohydrazide derivatives showed activity against LaArg with Ki in the range of 1.3-26 µM. The study of the kinetics of LaArg inhibition showed that these substances might act via different inhibitory mechanisms or even by a combination of these. The compounds were tested against L. amazonensis promastigotes and the best result was obtained to the compound 4 (EC50 of 12.7 ±â€¯0.3 µM). In addition, in order to obtain further insight into the binding mode of such compounds, molecular docking studies were performed to obtain additional validation of experimental results. Considering these results, it is possible to conclude that α,α-difluorohydrazide derivatives are a promising scaffold in the development of new substances against the etiological agent of leishmaniasis by targeting LaArg.

What about vaginal extraction of the kidney? results of an online survey.

PURPOSE: We aimed to characterize surgeons opinion about the vaginal extraction of the kidney after transperitoneal laparoscopic nephrectomy. Matherial and Methods: A 9-item questionnaire was published online (Survey Monkey TM) and publicized via email to a multidisciplinary pool of surgeons in Portugal. Data was collected and statistical analysis was performed using IBM SPSS Statistics, Version 21.0. RESULTS: Three hundred and fifty nine inquiries were sent, 154 surgeons completed the questionnaires (response rate of 43.0%). Fifty five point eight percent of the participants would choose the transvaginal approach for themselves or for a close relative. The most stated arguments were a better cosmesis (29.0%) expectancy of lower post operative pain (26.0%) and lower rate of incisional hernias (23.0%). Defenders of the transabdominal procedure justified with an expectancy of lower complication rate (39%), namely impairment of sexual function and fertility (22%). The female gender and the familiarity with transvaginal surgery were the stronger predictors of the option for this approach (70.6% vs 48.5%; p=0,016 and 85.3% vs 46.6%; p <0.001 respectively). CONCLUSIONS: Contrasting with similar surveys published on transvaginal NOTES, the vaginal specimen extraction after conventional laparoscopic nephrectomy was fairly accepted by the inquired surgeons.

Tackling the challenges of human Chagas disease: A comprehensive review of treatment strategies in the chronic phase and emerging therapeutic approaches.

Chagas disease (CD), caused by the flagellated protozoan Trypanosoma cruzi (T. cruzi), affects approximately 7 million people worldwide and is endemic in Latin America, especially among socioeconomically disadvantaged populations. Since the 1960s, only two drugs have been commercially available for treating this illness: nifurtimox (NFX) and benznidazole (BZN). Although these drugs are effective in the acute phase (AP) of the disease, in which parasitemia is usually high, their cure rates in the chronic phase (CP) are low and often associated with several side effects. The CP is characterized by a subpatent parasitaemia and absence of clinical symptoms in the great majority of infected individuals. However, at least 30 % of the individuals will develop potentially lethal symptomatic forms, including cardiac and digestive manifestations. For such reason, in the CP the treatment is usually symptomatic and typically focuses on managing complications such as arrhythmias, heart failure, or digestive problems. Therefore, the need for new drugs or therapeutic approaches using BZN or NFX is extremely urgent. This review presents the main clinical trials, especially in the CP, which involve BZN and NFX in different treatment regimens. Additionally, other therapies using combinations of these drugs with other substances such as allopurinol, itraconazole, ravuconazole, ketoconazole, posaconazole and amiodarone are also reported. The importance of early diagnosis, especially in pediatric patients, is also discussed, emphasizing the need to identify the disease in its early stages to improve the chances of successful treatment.

Study of the dynamic behavior of the cruzain enzyme in free and complexed forms with competitive and noncovalent benzimidazole inhibitors.

There are only two drugs for the treatment of Chagas disease, namely, nifurtimox and benznidazole, that can cause several adverse effects. Despite the effectiveness of these drugs in the disease's acute phase, they are not recognized as curative in the chronic phase, establishing the need for more effective treatment in all stages of the disease. Cruzain is an enzyme that plays a vital role in the life cycle of the etiologic agent, the protozoan Trypanosoma cruzi, being relevant as a therapeutic target in the planning of new drugs. Using molecular docking and dynamics simulations, we have investigated the structural and dynamic factors that can be involved in the enzyme inhibition process at the atomic-molecular level by benzimidazole compounds that are potent cruzain inhibitors with in vitro trypanocidal activity. The study suggests that these inhibitors bind cruzain through steric and hydrogen bonding interactions without altering its secondary structure content and protein compaction. Besides, we observed that these inhibitors decrease the correlation of movements between Cα-atoms of cruzain, increasing the number of atomic communities, mainly in the α-helix that presents the catalytic Cys25 residue. As expected, we also observed a correlation between the inhibitory activity of each inhibitor and their respective binding-free energies, reinforcing that the affinity of the complexes seems to be a relevant factor for enzymatic inhibition. Hence, the results presented in this work contribute to a better understanding of the cruzain enzyme inhibition mechanism through competitive and non-covalent inhibitors.Communicated by Ramaswamy H. Sarma.

In silico and in vitro assessment of anti-Trypanosoma cruzi efficacy, genotoxicity and pharmacokinetics of pentasubstituted pyrrolic Atorvastatin-aminoquinoline hybrid compounds.

Atorvastatin (AVA) is a third-generation statin with several pleiotropic effects, considered the last synthetic pharmaceutical blockbuster. Recently, our group described the effects of AVA on DNA damage prevention and against Trypanosoma cruzi infection. In this study, our aim was to evaluate the efficacy, safety, and in silico pharmacokinetic profile of four hybrids of aminoquinolines with AVA 4a-d against T. cruzi using in vitro and in silico models. These synthetic compounds were designed by hybridization of the pentapyrrolic moiety of AVA with the aminoquinolinic unit of chloroquine or primaquine. Pharmacokinetics (ADME) and toxicity parameters were predicted by SwissADME, admetSAR and LAZAR in silico algorithms. The trypanocidal activity of AVA-quinoline hybrids were evaluated in vitro against amastigotes and trypomastigotes of T. cruzi, from Y (Tc II) and Tulahuen (Tc VI) strains. In vitro cardiocytotoxicity was assessed using primary cultures of mouse embryonic cardiac cells and in vitro hepatocytotoxicity on bidimensional and 3D-cultured HepG2 cells. Genotoxicity was evaluated by Ames test and micronucleus assay. Despite the overall good in silico ADMET profile, all tested compounds were predicted to be hepatotoxic. All hybrid derivatives presented high trypanocidal activity, against both trypomastigote and intracellular forms of T. cruzi, presenting EC50's lower than 1 µM besides superior selectivity than the reference drug, without evidences of cardiotoxicity in vitro. The compounds 4a and 4b presented a time-dependent toxicity in monolayer culture of HepG2 but no detectable toxic effects in their spheroids, opposing to the in silico prediction. We can conclude that the AVA-aminoquinoline hybrids presented a hit profile as antiparasitic agents in synthetic pharmaceutical innovation platforms.

Transvesical natural orifice transluminal endoscopic surgery (NOTES) nephrectomy with kidney morcellation: a proof of concept study.

UNLABELLED: Study Type - Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Until now, the transvaginal approach has been the only method of removing larger specimens from the abdominal cavity using natural orifice transluminal endoscopic surgery. There has been no means of extracting larger specimens in men and the means are restricted even in women, particularly in young women. The present study shows that the difficulty of large specimen retrieval can be overcome, irrespective of the diameter of the chosen port, through natural orifices using morcellation. OBJECTIVE: To show, in a porcine model, the feasibility of a complete transvesical natural orifice transluminal endoscopic surgery (NOTES) nephrectomy with kidney extraction after morcellation through the same port. MATERIALS AND METHODS: Transvesical nephrectomy and morcellation were performed in six pigs at Minho University, Braga, Portugal after institutional review board approval. The transvesical port and the cystotomy were created under the guidance of a ureteroscope, while the remaining steps were done under the guidance of an operating telescope. Dissection of the renal vessels and kidney was performed using dissection grasping forceps and a vessel sealing system (LigaSure(™) ; Covidien, Mansfield, MA, USA) and morcellation was done using a Piranha(™) morcellator (Richard Wolf, Knittlingen, Germany). RESULTS: There were no complications related to the creation of transvesical access. The image provided by the telescope was superior to that of the ureteroscope, especially underwater. Morcellation was quick and effective, with the support of a fixing needle through the abdominal wall, designed to fix the kidney, after laceration of a bowel loop occurred in the first experiment. It was found that technical improvements are needed to ensure safety of NOTES morcellation. CONCLUSIONS: Kidney morcellation after nephrectomy, using a natural orifice exclusively, is feasible. Despite technical limitations, this proof of concept study can be regarded as a potential step towards the application of NOTES in urology.

The cleavage kinetics of hydrazide derivatives of isoniazid by HPLC-UV/DAD and its impact on activity against Mycobacterium tuberculosis.

Isoniazid is a first-line drug for the treatment of tuberculosis, a bacterial disease caused by Mycobacterium tuberculosis. Its terminal amino group is highly reactive, leading to significant metabolic deactivation, drug interactions and hepatotoxicity. It is speculated that the activity of isoniazid derivatives is, in part, related to the cleavage of the protecting group. Therefore, this study aimed to evaluate the cleavage characteristics of previously developed isoniazid derivatives through kinetic studies by high-performance liquid chromatography with ultraviolet-diode array detectio to establish a comparison between the rates of the process and the respective activities against M. tuberculosis. Chromatographic separations were performed on an XDB C18 column coupled to an XDB C18 precolumn. The mobile phase consisted of ultrapure water and acetonitrile in gradient mode. The flow rate was 1.0 mL/min, the injection volume was 20 µL, and the detection wavelengths were 230 nm (derivatives and isatins) and 270 nm (isoniazid). Incubation of derivatives was carried out for 5 days in 10 mmol/L phosphate buffer solution (pH 3.0, 7.4, 8.0) or in fetal bovine serum at 37 °C. The incubation reduced the concentration of the derivatives and led to the formation of isoniazid in a first-order kinetic reaction. Isoniazid formation was logarithmically correlated with the minimum inhibitory concentration of the derivatives. The results showed that higher cleavage rates are associated with greater activities against M. tuberculosis, providing important information for the development of future generations of isoniazid derivatives and for screening drug candidates for the treatment of tuberculosis.

Novel 2-Nitroimidazole and Imidazooxazole Derivatives and their Activity against Trypanosoma cruzi and Mycobacterium tuberculosis.

BACKGROUND: Tuberculosis (TB) is one of the top ten causes of death worldwide, while Chagas disease (CD) is the parasitic disease that kills the largest number of people in the Americas. TB is the leading cause of death for patients with AIDS; it kills 1.5 million people and causes 10 million new cases every year. The lack of newly developed chemotherapeutic agents and insufficient access to health care services for a diagnosis increase the incidence of multidrug-resistant TB (MDRTB) cases. Although CD was identified in 1909, the chronic stages of the disease still lack adequate treatment. OBJECTIVE: The purpose of this work was to design and synthesize two new series of 2-nitroimidazole 5a-e and imidazooxazoles 6a-e with 1H-1,2,3-triazolil nucleus and evaluate their activities against Tc and Mycobacterium tuberculosis (Mtb). METHODS: Two series of five compounds were synthesized in a 3 or 4-step route in moderated yields, and their structures were confirmed by NMR spectral data analyses. The in vitro antitrypanosomal evaluation of products was carried out in an intracellular model using L929 cell line infected with trypomastigotes and amastigote forms of Tc of ß-galactosidase-transfected Tulahuen strain. Their antimycobacterial activity was evaluated against Mtb strain H37Rv. RESULTS: In general, 2-nitroimidazolic derivatives proved to be more potent in regard to antitrypanocidal and antimycobacterial activity. The non-cytotoxic 2-nitroimidazole derivative 5b was the most promising with a half maximum inhibitory concentration of 3.2 µM against Tc and a minimum inhibitory concentration of 65.3 µM against Mtb. CONCLUSION: Our study reinforced the importance of 2-nitroimidazole and 1H-1,2,3-triazole nuclei in antimicrobial activity. In addition, derivative 5b proved to be the most promising, presenting important activity against Tc and Mtb and could be used as a starting point for the development of new agents against these diseases.

Transvesical peritoneoscopy with rigid scope: feasibility study in human male cadaver.

BACKGROUND: Transvesical port refers to the method of accessing the abdominal cavity through a natural orifice (i.e., urethra) under endoscopic visualization. Since its introduction in 2006, various reports have been published describing different surgical interventions using a rigid ureteroscope in a porcine model. The aim of this study was to test the access and feasibility of peritoneoscopy by using a rigid ureteroscope in a human male cadaver. METHODS: Two adult male cadavers were used to perform the procedures. A rigid ureteroscope was used for the creation of transvesical access into the peritoneal cavity. Peritoneoscopy, liver biopsy, and identification and manipulation of the ileocecal appendix were performed. RESULTS: Transvesical access into the peritoneal cavity was quickly established. The rigid ureteroscope easily allowed visualization of the abdominal cavity with good image quality. Liver biopsy and manipulation of ileocecal appendix were carried out without difficulties. CONCLUSIONS: Peritoneoscopy, liver biopsy, and ileocecal appendix manipulation using a rigid ureteroscope through a transvesical port is feasible in a cadaver model. The development of a specific rigid scope for the transvesical port might herald a promising future for this NOTES access.

The quality of reporting of randomized controlled trials in pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Randomized controlled trials (RCTs) must comply with the strict rules of design and conduct and their reporting should reflect it. Our aim was to evaluate how the quality of RCT reporting in pelvic organ prolapse (POP) has evolved. METHODS: RCTs in POP published between 1997 and 2010 were retrieved through a PubMed search. The quality of reporting was assessed by applying the 2010 revised Consolidated Standards of Reporting Trials (CONSORT) statement. Appropriate statistical analysis was performed. RESULTS: Forty-one RCTs were identified for review. The implementation of randomization, recruitment, blinding, outcomes with effect size and precision, trial registration, and full protocol availability were reported in less than half of the trials. Comparing two periods (1997-2006 and 2007-2010), there was no improvement in the quality of reporting for any of the CONSORT criteria. CONCLUSIONS: RCTs in POP are scarce. The quality of reporting is suboptimal in many aspects and has not improved in recent years.

Endoscopic removal of an intravesical calcified sling using pneumatic lithotripsy and cystoscopic resection.

The transobturator tape procedure is a minimally invasive treatment for stress urinary incontinence. The widespread use of these slings has led to an increase in the number of rare complications, such as bladder erosion. Although in the last few years several minimally invasive techniques have been described, surgical management of such complications remains an open issue. We report a case of a bladder stone formed on a transobturator sling after unrecognized bladder perforation. Using pneumatic lithotripsy, the calculus was fragmented and the intravesical portion of the tape was successfully excised and removed by transurethral resection and endoscopic scissors. This minimally invasive transurethral technique is challenging but can be a safe and successful way to deal with such rare complications.