Efficacy and safety of skeletonized mesh implants for advanced pelvic organ prolapse: 12-month follow-up

Objective

To evaluate the efficacy and safety of skeletonized mesh implants for advanced pelvic organ prolapse (POP).

Methods

Women with advances POP underwent repair of stage III or greater anterior or posterior and apical compartment prolapse using skeletonized mesh implants (Seratom PA MR MN^® system—SERAG-WIESSNER, Naila, Germany). Anatomical outcomes were assessed using pelvic organ prolapse quantification staging and functional outcomes were self-reported by the patients at 6 weeks, 6 and 12 months. Anatomical and functional cure rates, post-operative pain and dyspareunia as well as intra and post-operative complications were reported. Success was defined as a composite of no bulge symptoms and no prolapse beyond the hymenal ring.

Results

At 12 months, data were available for 103 of the 105 patients originally recruited. Intra-operative complications included 2 (2 %) cases of cystotomy that were corrected vaginally. The immediate post-operative complications included 1 patient (1 %) with UTI, 4 (3.9 %) cases of self-resolved hematomas, and 6 (5.8 %) cases of bladder outlet obstruction. At 12 months, a high success rate and low complication rate was noted. Recurrence of prolapse was reported by 7 (6.6 %) patients. However, only 4 (3.8 %) underwent a repeat procedure. Two patient developed de novo SUI, and 6 (5.7 %) developed dyspareunia. No cases of mesh erosion/extrusion were noted.

Conclusion

The present study showed excellent anatomical and quality of life results in patients with advanced POP treated with a skeletonized and reduced mesh system. No mesh exposure was recorded within the first year after surgery.

     

Optogenetic inhibition of cortical afferents in the nucleus accumbens simultaneously prevents cue-induced transient synaptic potentiation and cocaine-seeking behavior

Animal models of relapse reveal that the motivation to seek drug is regulated by enduring morphological and physiological changes in the nucleus accumbens, as well as transient synaptic potentiation in the accumbens core (NAcore) that parallels drug-seeking behavior. The current study sought to examine the link between the behavioral and synaptic consequences of cue-induced cocaine seeking by optically silencing glutamatergic afferents to the NAcore from the prelimbic cortex (PL). Adeno-associated virus coding for the inhibitory opsin archaerhodopsin was microinjected into PL, and optical fibers were targeted to NAcore. Animals were trained to self-administer cocaine followed by extinction training, and then underwent cue-induced reinstatement in the presence or absence of 15 min of optically induced inhibition of PL fibers in NAcore. Inhibiting the PL-to-NAcore projection blocked reinstated behavior and was paralleled by decreased dendritic spine head diameter and AMPA/NMDA ratio relative to sham-laser control rats. Interestingly, while spine density was elevated after extinction training, no further effects were observed by cued reinstatement or optical inhibition. These findings validate the critical role for PL afferents to the NAcore in simultaneously regulating both reinstated behavior and the associated transient synaptic potentiation.     

The association between adverse childhood experiences and common mental disorders and suicidality: an umbrella review of systematic reviews and meta-analyses

European Child & Adolescent Psychiatry - Adverse childhood experiences (ACEs) are related to increased risk of common mental disorders. This umbrella review of systematic reviews and...     

Opportunities for Early Intervention to Avoid Prolonged Work Disability: Introduction to the Special Section

Purpose The articles in this special section examine opportunities for early intervention that is intended to retain the jobs of workers who have medical conditions that could put them at risk of prolonged work disability. Methods The first three articles examine options for analyzing various types of disability claims data for targeting early intervention; the fourth article provides new information from 50 case studies on how employers decide to invest in the retention of individual workers. Results Together, the four articles demonstrate that there may be an opportunity to positively affect longer-term outcomes for workers with medical conditions. This would be accomplished by building and expanding on existing systems in order to efficiently identify, and provide timely support to, workers with medical conditions in a critical period during which the decisions and actions of various stakeholders, including the workers themselves, may have a major influence on these outcomes. Conclusions Forthcoming opportunities to develop, implement, and test evidence-based interventions to promote job retention can provide further insight into the value of the options described in the articles.     

Using Predictive Analytics for Early Identification of Short-Term Disability Claimants Who Exhaust Their Benefits

Purpose Early interventions can help short-term disability insurance (STDI) claimants return to work following onset of an off-the-job medical condition. Accurately targeting such interventions involves identifying claimants who would, without intervention, exhaust STDI benefits and transition to longer-term support. We identify factors that predict STDI exhaustion and transfer to long-term disability insurance (LTDI). We also explore whether waiting for some claims to resolve without intervention improves targeting efficiency. Methods We use a large database of STDI claims from private employer-sponsored disability insurance programs in the United States to predict which claims will exhaust STDI or transition to LTDI. We use a split sample approach, conducting logistic regressions on half of our data and generating predictions for the other half. We assess predictive accuracy using ROC curve analysis, repeating on successive subsamples, omitting claims that resolve within 2, 4, and 6 weeks. Results Age, primary diagnosis, and employer industry were associated with the two outcomes. Rapid attrition of short-duration claims from the sample means that waiting can substantially increase the efficiency of targeting efforts. Overall accuracy of classification increases from 63.2% at week 0 to 82.9% at week 6 for exhausting STDI benefits, and from 63.7 to 83.0% for LTDI transfer. Conclusions Waiting even a few weeks can substantially increase the accuracy of early intervention targeting by allowing claims that will resolve without further intervention to do so. Predictive modeling further narrows the target population based on claim characteristics, reducing intervention costs. Before adopting a waiting strategy, however, it is important to consider potential trade-offs involved in delaying the start of any intervention.     

A two phase harmonic model for left ventricular function

A minimal model for mechanical motion of the left ventricle is proposed. The model assumes the left ventricle to be a harmonic oscillator with two distinct phases, simulating the systolic and diastolic phases, at which both the amplitude and the elastic constant of the oscillator are different. Taking into account the pressure within the left ventricle, the model shows qualitative agreement with functional parameters of the left ventricle. The model allows for a natural explanation of heart failure with preserved systolic left ventricular function, also termed diastolic heart failure. Specifically, the rise in left ventricular filling pressures following increased left-ventricular wall stiffness is attributed to a mechanism aimed at preserving heart rate and cardiac output.     

Tissue inhibitor of metalloproteinase-3 via oncolytic herpesvirus inhibits tumor growth and vascular progenitors

Malignant solid tumors remain a significant clinical challenge, necessitating innovative therapeutic approaches. Oncolytic viral therapy is a nonmutagenic, biological anticancer therapeutic shown to be effective against human cancer in early studies. Because matrix metalloproteinases (MMP) play important roles in the pathogenesis and progression of cancer, we sought to determine if "arming" an oncolytic herpes simplex virus (oHSV) with an MMP-antagonizing transgene would increase virus-mediated antitumor efficacy. We generated oHSVs that express human tissue inhibitor of metalloproteinases 3 (TIMP3) or firefly luciferase and designated them rQT3 and rQLuc, respectively. We evaluated the antitumor efficacy of these viruses against neuroblastoma and malignant peripheral nerve sheath tumor (MPNST) xenografts. Relative to rQLuc, rQT3-infected primary human MPNST and neuroblastoma cells exhibited equivalent virus replication but increased cytotoxicity and reduced MMP activity. In vivo, rQT3-treated tumors showed delayed tumor growth, increased peak levels of infectious virus, immature collagen extracellular matrix, and reduced tumor vascular density. Remarkably, rQT3 treatment reduced circulating endothelial progenitors, suggesting virus-mediated antivasculogenesis. We conclude that rQT3 enhanced antitumor efficacy through multiple mechanisms, including direct cytotoxicity, elevated virus titer, and reduced tumor neovascularization. These findings support the further development of combined TIMP-3 and oncolytic virotherapy for cancer.     

Chills During Hemodialysis: Prediction and Prevalence of Bacterial Infections – A Retrospective Cohort Study

Introduction

Chills are a complication of patients undergoing hemodialysis. The rate of infection among hemodialysis patients presenting with chills is not well established, and empirical broad-spectrum antibiotics are usually the rule.