Cyanoacrylate mesh fixation for laparoscopic inguinal hernia repair: a prospective, multicenter, single-arm study.

BACKGROUND: Inguinal hernia repair is among the most frequently performed surgical procedures. Alternatives to penetrating mesh fixation, such as surgical glue, are being investigated for their potential benefit in reducing chronic pain. The aim of this study was to assess the efficacy of the n-hexyl cyanoacrylate glue Ifabond™ for mesh fixation in laparoscopic inguinal hernia repair. METHODS: This prospective, multicenter, single-arm study collected data from laparoscopic inguinal hernia repairs using Ifabond™ (Peters Surgical, Boulogne-Billancourt Cedex, France) and a standard [Promesh® SURG ST (Peters Surgical)/Biomesh® P1 (Cousin Biotech, Wervicq-Sud, France)] or lightweight [Promesh® SURG LI (Peters Surgical)/Premium® Implant (Cousin Biotech)] polypropylene mesh. The primary endpoint was postoperative pain [100-scale Visual Analog Scale (VAS)]. Secondary endpoints were complications, hernia recurrences, and quality of life (QoL) (EQ-5D-3L health index and EQ-VAS). Patients were followed up at 5 weeks and 12 months after surgery. RESULTS: Six-hundred and thirteen patients underwent laparoscopic inguinal hernia repair. Postoperative pain decreased at 5-week (3.97 ± 10.04; p < 0.0001) and 12-month (3.83 ± 11.26; p < 0.0001) follow-up compared with before surgery (26.96 ± 19.42). One hundred and fifteen patients (13.74%) experienced chronic pain in the groin at 12-month follow-up, of whom 14 (2.67%) required analgesics. There were 6 patients with major morbidities and one patient died of an unrelated cause. Two hernia recurrences occurred within 12-month follow-up. Patients' QoL increased from an EQ-5D-3L index score of 0.82 ± 0.19 preoperatively to 0.90 ± 0.15 at 5 weeks (p < 0.0001) and 0.92 ± 0.15 at 12 months after surgery (p < 0.0001). The EQ-VAS general health scoring increased from 79.03 ± 12.69 preoperatively to 84.31 ± 9.97 at 5-week (p < 0.0001) and 84.16 ± 14.48 at 12-month follow-up (p < 0.0001). CONCLUSIONS: Ifabond™ (Peters Surgical) is a safe, reliable, and feasible fixation method for laparoscopic inguinal hernia repair with a very high surgeon satisfaction score, improved patients' QoL, and comparable risk of developing chronic pain and postoperative complications as described in the literature.

A foundation for reference models for drug combinations with an application to Loewe's reference model.

BACKGROUND: Treating patients with combinations of drugs that have synergistic effects has become widespread practice in the clinic. Drugs work synergistically when the observed effect of a drug combination is larger than the effect predicted by the reference model. The reference model is a theoretical null model that returns the combined effect of given doses of drugs under the assumption that these drugs do not interact. There is ongoing debate on what it means for drugs to not interact. The controversy transcends mathematical punctuality, as different non-interaction principles result in different reference models. A famous reference model that has been in existence for already a long time is Loewe's reference model. Loewe's vision on non-interaction was purely intuitive: two drugs do not interact if all combinations of doses that result in a certain given effect lie on a straight line. RESULTS: We show that Loewe's reference model can be obtained from much more fundamental principles. First, we introduce the new notion of complementary dose. Secondly, we reformulate the existing concept of equivalent dose, whereby our formulation is more general than existing ones. Finally, a very general non-interaction principle is put forward. The proposed non-interaction principle represents a certain interplay between complementary and equivalent doses: drugs are non-interacting if complementarity is preserved under equivalence. It is then shown that Loewe's reference model naturally follows from these principles by an appropriate choice of complementarity. CONCLUSIONS: The presented work increases insight into Loewe's reference model for drug combinations, which is realized by the introduction of a very general non-interaction principle that does not refer to any specific dose-response curve, nor to any property of applicable dose-response curves.

Clustering of gene expression profiles: creating initialization-independent clusterings by eliminating unstable genes.

Clustering is an important approach in the analysis of biological data, and often a first step to identify interesting patterns of coexpression in gene expression data. Because of the high complexity and diversity of gene expression data, many genes cannot be easily assigned to a cluster, but even if the dissimilarity of these genes with all other gene groups is large, they will finally be forced to become member of a cluster. In this paper we show how to detect such elements, called unstable elements. We have developed an approach for iterative clustering algorithms in which unstable elements are deleted, making the iterative algorithm less dependent on initial centers. Although the approach is unsupervised, it is less likely that the clusters into which the reduced data set is subdivided contain false positives. This clustering yields a more differentiated approach for biological data, since the cluster analysis is divided into two parts: the pruned data set is divided into highly consistent clusters in an unsupervised way and the removed, unstable elements for which no meaningful cluster exists in unsupervised terms can be given a cluster with the use of biological knowledge and information about the likelihood of cluster membership. We illustrate our framework on both an artificial and real biological data set.