Introducing a true minimally invasive meshless and dissectionless anchoring system for pelvic organ prolapse repair

Introduction and hypothesis

The objective was to demonstrate the biomechanical properties, feasibility, and potential advantages over conventional techniques of this new anchoring device, NeuGuide?.

Methods

We evaluated the pull-out forces required to pull the NeuGuide? anchor elements from a uniform porcine ligament and a cadaver ligament. We also evaluated the function of the NeuGuide? and the characteristics of the device for the establishment of verification evidence ensuring the reliability and feasibility of the device. We also evaluated the safety and performance of the NeuGuide? procedure in female cadavers by palpating the sacro-spinous ligament in real time. We assessed the ability to deploy and fixate the anchor to the sacro-spinous ligament and to stitch the sutures from both sides of the vaginal apex to the cervix, without damaging the surrounding structures.

Results

All 12 anchors were inserted into the porcine ligament and the cadaver sacro-spinous ligaments successfully (mean pull-out force 34.13?±?4.32 and 35.68?±?9.28 respectively). None of the measured forces were below 20 N. No statistically significant difference was noted in the pull-out forces between the porcine and the cadavers (p?=?0.60), between the two cadavers (p?=?0.19) and between the right and left sacro-spinous ligaments. No abnormalities or malfunctions were noted in the functional performance of the device. Upon laparotomy, dissection of the cadavers revealed that the sacro-spinous ligaments were reached safely with no damage to the surrounding organs and tissues.

Conclusions

This novel anchoring device (NeuGuide?) is aimed at facilitating a durable, easy, and short procedure for sacro-spinous ligament fixation with hypothetically fewer operative complications.

     

Cryopreservation of day 2–3 embryos by vitrification yields better outcome than slow freezing

Objective: To compare the outcome of vitrification versus slow freezing cryopreservation for cleavage stage day 2–3 embryos.

Design: A retrospective observational study.

Setting: All thawed embryos assisted reproduction cycles between January 2010 and December 2012 at a single IVF laboratory of a Tertiary Medical Center.

Patients: Five hundred and thirty-nine cycles of day 2–3 thawed embryos.

Interventions: In 327 of the thawed cycles, the embryos were vitrified and in 212 of the cycles the embryos were derived from slow freezing embryos.

Main outcomes measure: Embryo survival rate, blastomere surviving rate and pregnancy rate.

Results: Embryo survival rate was significantly higher after vitrification compared with slow freezing (81.6%, 647/793 versus 70.0%, 393/562 embryos, p?p?=?0.02).

Conclusions: Vitrification of day 2–3 cleavage stage embryos yields better cycle outcome in all the parameters compared to slow freezing.     

Role of the decreased nitric oxide bioavailability in the vascular complications of diabetes mellitus

This mini-review takes into consideration the physiology, synthesis and mechanisms of action of the nitric oxide (NO) and, subsequently, the causes and effects of the NO bioavailability impairment. In diabetes mellitus the reduced NO bioavailability is caused by the increased free radicals production, secondary to hyperglycemia. The reactive oxygen species oxidize the cofactors of the nitric oxide synthase, diminishing their active forms and consequently leading to a decreased NO production. Furthermore the decreased concentration of reduced glutathione results in a diminished production of nitrosoglutathione. These molecules are important intermediates of the NO pathway and physiologically activate the soluble guanylate cyclase. Their decrease in oxidative states of the cell, therefore, leads to a reduced cGMP production which represents the principal molecule that carries out NO's major effects. Finally we considered the eventual therapeutic strategies to improve NO bioavailability by acting on the causes of its decrease. Therefore the treatments proposed are based on the possibility to counteract the oxidation and, in this context, the physiopathological mechanisms strongly support the treatment with thiols.     

Assessing hospital electronic health record vendor performance across publicly reported quality measures

ObjectiveLittle is known regarding variation among electronic health record (EHR) vendors in quality performance. This issue is compounded by selection effects in which high-quality hospitals coalesce to a subset of market leading vendors. We measured hospital performance, stratified by EHR vendor, across 4 quality metrics.Materials and MethodsWe used data on 1272 hospitals in 2018 across 4 quality measures: Leapfrog Computerized Provider Order Entry/EHR Evaluation, Centers for Medicare and Medicaid Services Hospital Compare Star Ratings, Hospital-Acquired Condition (HAC) score, and Hospital Readmission Reduction Program (HRRP) ratio. We examined score distributions and used multivariable regression to evaluate the association between vendor and score, recovering partial R² to assess the proportion of quality variation explained by vendor.ResultsWe found significant variation across and within EHR vendors. The largest vendor, vendor A, had the highest mean score on the Leapfrog Computerized Provider Order Entry/EHR Evaluation and HRRP ratio, vendor G had the highest Hospital Compare score, and vendor F had the highest HAC score. In adjusted models, no vendor was significantly associated with higher performance on more than 2 measures. EHR vendor explained between 1.2% (HAC) and 7.6 (HRRP) of the variation in quality performance.DiscussionNo EHR vendor was associated with higher quality across all measures, and the 2 largest vendors were not associated with the highest scores. Only a small fraction of quality variation was explained by EHR vendor choice.ConclusionsTop performance on quality measures can be achieved with any EHR vendor; much of quality performance is driven by the hospital and how it uses the EHR.     

Should pre-implantation genetic screening be implemented to routine clinical practice?

The utilization of trophectoderm biopsy combined with comprehensive chromosome screening (CCS) tests for embryonic aneuploidy was recently suggested to improve IVF outcome, however, not without criticisms. Since mosaicism has been reported in as high as 90% of blastocyst-stage embryos, we aimed to evaluate the accuracy of trophectoderm multiple biopsies using next-generation sequencing (NGS). Eight top quality blastocysts underwent three trophectoderm biopsies each, followed by NGS. In four blastocysts, the rest of the embryo, which included the inner cell mass, was also analyzed. Five of the 24 (20.8%) trophectoderm biopsies revealed inconclusive results, while 4 (16.6%) demonstrated embryonic mosaicism. Overall, 10 (35.7%) of the 28 (24 trophectoderms and 4 inner cell masses) biopsies revealed mosaicism or inconclusive results. Our preliminary observations contribute to the ongoing discussion on the unrestricted clinical adoption of PGS, suggesting, that until proper evaluation of its effectiveness and cost-effectiveness will be provided, PGS should be offered only under study conditions, and with appropriate informed consents.     

Probing the Binding Pocket of the Broadly Tuned Human Bitter Taste Receptor TAS2R14 by Chemical Modification of Cognate Agonists

Sensing potentially harmful bitter substances in the oral cavity is achieved by a group of ^?25 receptors, named TAS2Rs, which are expressed in specialized sensory cells and recognize individual but overlapping sets of bitter compounds. The receptors differ in their tuning breadths ranging from narrowly to broadly tuned receptors. One of the most broadly tuned human bitter taste receptors is the TAS2R14 recognizing an enormous variety of chemically diverse synthetic and natural bitter compounds, including numerous medicinal drugs. This suggests that this receptor possesses a large readily accessible ligand binding pocket. To allow probing the accessibility and size of the ligand binding pocket, we chemically modified cognate agonists and tested receptor responses in functional assays. The addition of large functional groups to agonists was usually possible without abolishing agonistic activity. The newly synthesized agonist derivatives were modeled in the binding site of the receptor, providing comparison to the mother substances and rationalization of the in vitro activities of this series of compounds.     

Localized scleroderma in childhood is not just a skin disease

OBJECTIVE: Juvenile localized scleroderma is usually considered a disease that is confined to the skin and subcutaneous tissue. We studied the prevalence and clinical features of extracutaneous manifestations in a large cohort of children with juvenile localized scleroderma. METHODS: Data from a multinational study on juvenile scleroderma was used for this in-depth study. Clinical features of patients with extracutaneous manifestations were compared with those of patients who had exclusively skin involvement. RESULTS: Seven hundred fifty patients entered the study. One hundred sixty-eight patients (22.4%) presented with a total of 193 extracutaneous manifestations, as follows: articular (47.2%), neurologic (17.1%), vascular (9.3%), ocular (8.3%), gastrointestinal (6.2%), respiratory (2.6%), cardiac (1%), and renal (1%). Other autoimmune conditions were present in 7.3% of patients. Neurologic involvement consisted of epilepsy, central nervous system vasculitis, peripheral neuropathy, vascular malformations, headache, and neuroimaging abnormalities. Ocular manifestations were episcleritis, uveitis, xerophthalmia, glaucoma, and papilledema. In more than one-fourth of these children, articular, neurologic, and ocular involvements were unrelated to the site of skin lesions. Raynaud's phenomenon was reported in 16 patients. Respiratory involvement consisted essentially of restrictive lung disease. Gastrointestinal involvement was reported in 12 patients and consisted exclusively of gastroesophageal reflux. Thirty patients (4%) had multiple extracutaneous features, but systemic sclerosis (SSc) developed in only 1 patient. In patients with extracutaneous involvement, the prevalence of antinuclear antibodies and rheumatoid factor was significantly higher than that among patients with only skin involvement. However, Scl-70 and anticentromere, markers of SSc, were not significantly increased. CONCLUSION: Extracutaneous manifestations of juvenile localized scleroderma developed in almost one-fourth of the children in this study. These extracutaneous manifestations often were unrelated to the site of the skin lesions and sometimes were associated with multiple organ involvement. The risk of developing SSc was very low. This subgroup of patients with juvenile localized scleroderma should be evaluated extensively, treated more aggressively, and monitored carefully.