AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

La suspension latérale cœlioscopique, une autre façon de traiter les prolapsus génitaux [Laparoscopic lateral suspension, another way to treat genital prolapse]

The laparoscopic sacrocolpopexy is the treatment of choice of pelvic organ prolapses since more than twenty years. The laparoscopic lateral suspension with mesh is an alternative technique. Its originality is the subperitoneal passing of the lateral arm of the mesh in the lateral abdominal wall, leaving the skin above the iliac crest, in a place without risks of vascular, nerve, bowel injuries. We report in this article the results of the three main publications on the subject. The indications are cystocele and apical descent. It can be envisaged when the access of the promontory is difficult; for instance in the presence of obesity, adhesions, sigmoid megacolon, or low position of the left common iliac vein, partially covering the promontory. It is also a practical technique for surgeons having a moderate experience of the promontory access

Can we harness the placebo effect to improve care in lower urinary tract dysfunction? ICI-RS 2019

The proposal "Can we harness the placebo effect to improve care in lower urinary tract dysfunction?" was discussed at the International Consultation on Incontinence-Research Society (ICI-RS) 2019 meeting. The placebo effect can change the treatment outcome whether the treatment is an active treatment or placebo. The total active treatment outcome is a combination of the placebo and the active treatment effect which is seen in placebo-controlled trials. The placebo effect plays an important role in the treatment of lower urinary tract dysfunction in overactive bladder, bladder pain syndrome, and stress urinary incontinence. In clinical practice, a number of factors can be employed to use the placebo effect to maximize its effect on patients receiving an active treatment, such as having the same environment for review such as the same appointment time, same room, and same clinician. Clinicians should also be aware of the nocebo effect which is increased with an overemphasis on side effects or negative outcomes

Laparoscopic Lateral Suspension: Benefits of a Cross-shaped Mesh to Treat Difficult Vaginal Vault Prolapse.

To show an original technique of laparoscopic lateral suspension (LLS) with a precut mesh in a difficult case of vaginal vault prolapse. Step-by-step descriptions of the technique using videos (educational video). Vaginal vault prolapse affects up to 1% of patients who had a hysterectomy. Sacrocolpopexy is considered the gold standard in the treatment of apical pelvic organ prolapse. However, dissection at the level of the promontory may be challenging, particularly in obese patients or when an anatomic variation exists. This may be associated with rare but serious neurologic or ureteral morbidity as well as life-threatening vascular injury. LLS with mesh represents an alternative procedure, avoiding dissection at the promontory. The originality of this video is to describe the procedure of LLS in a difficult case of vaginal vault prolapse related to adhesions and difficulties of fascia cleavage. The use of a precut cross-shaped mesh simplified the technique and facilitated the attachment of the mesh to the fascia and the lateral suspension for a smaller period of time. This point is not negligible, especially in cases with technical difficulties. Institutional review board approval was obtained through the local ethics committee of Geneva University Hospitals (Canadian Task Force classification III). After dissections, positioning of the mesh on the dome and on the anterior and posterior vaginal walls is explained. The out-in technique of lateral suspension with the specific mesh is described. In this difficult case of vaginal vault prolapse, the LLS using a precut cross-shaped mesh was placed in good conditions, providing the patient with a minimum risk of complications and with the benefits of minimally invasive approach

The efficacy of botulinum toxin A and sacral neuromodulation in the management of interstitial cystitis (IC)/bladder pain syndrome (BPS), what do we know? ICI-RS 2017 think thank, Bristol.

This manuscript aims to address the evidence availale in the literature on the efficacy of Botulinum Toxin A (BoNT-A) and sacral neuromodulation (SNM) in patients suffering from Interstitial Cystitis (IC)/BPS and propose further research to identify mechanisms of action and establish the clinical efficacy of either therapy. At the International Consultation on Incontinence-Research Society (ICI-RS) in 2017, a panel of Functional Urologists and Urogynaecologists participated in a Think Tank (TT) discussing the management of IC/BPS by BoNT-A and SNM, using available data from both PubMed and Medicine literature searches. The role of BoNT-A and SNM in the treatment of IC/BPS are discussed and mechanisms of actions are proposed. Despite the available randomized trial data on the effect of intravesical BoNT-A treatment on symptoms of IC/BPS, a consistent conclusion of a positive effect cannot be drawn at the moment, as the published studies are small and heterogeneous in design. There is substantive evidence for the positive effects of SNM on symptoms of IC/BPS patients however, during patient selection, it is important to distinguish the degree and the location of pain in order to tailor the best therapy to the right patients. Both intravesical BoNT-A treatment and SNM have been shown to have positive effects in patients with IC/BPS. However, firm conclusions cannot yet be drawn. Patient-reported outcomes and quality of life should be assessed in addition to urinary and pain symptoms. Since current treatments mainly focus on symptomatic relief, future research should also focus on clarifying the pathogenic mechanisms involved in IC/BPS