In vivo response to polypropylene following implantation in animal models: a review of biocompatibility

Introduction and hypothesis

Polypropylene is a material that is commonly used to treat pelvic floor conditions such as pelvic organ prolapse (POP) and stress urinary incontinence (SUI). Owing to the nature of complications experienced by some patients implanted with either incontinence or prolapse meshes, the biocompatibility of polypropylene has recently been questioned. This literature review considers the in vivo response to polypropylene following implantation in animal models. The specific areas explored in this review are material selection, impact of anatomical location, and the structure, weight and size of polypropylene mesh types.

Methods

All relevant abstracts from original articles investigating the host response of mesh in vivo were reviewed. Papers were obtained and categorised into various mesh material types: polypropylene, polypropylene composites, and other synthetic and biologically derived mesh.

Results

Polypropylene mesh fared well in comparison with other material types in terms of host response. It was found that a lightweight, large-pore mesh is the most appropriate structure.

Conclusion

The evidence reviewed shows that polypropylene evokes a less inflammatory or similar host response when compared with other materials used in mesh devices.

     

Three-dimensional volume rendering of pelvic models and paraurethral masses based on MRI cross-sectional images

Aims

Our aim was to assess the feasibility of rendering 3D pelvic models using magnetic resonance imaging (MRI) scans of patients with vaginal, urethral and paraurethral lesions and obtain additional information previously unavailable through 2D imaging modalities.

Methods

A purposive sample of five female patients 26-40 years old undergoing investigations for vaginal or paraurethral mass was obtained in a tertiary teaching hospital. 3D volume renderings of the bladder, urethra and paraurethral masses were constructed using 3D-Slicer v.3.4.0. Spatial dimensions were determined and compared with findings from clinical, MRI, surgical and histopathological reports.The quality of information regarding size and location of paraurethral masses obtained from 3D models was compared with information from cross-sectional MRI and review of clinical, surgical and histopathological findings.

Results

The analysis of rendered 3D models yielded detailed anatomical dimensions and provided information that was in agreement and in higher detail than information based on clinical examination, cross-sectional 2D MRI analysis and histopathological reports. High-quality pelvic 3D models were rendered with the characteristics and resolution to allow identification and detailed viewing of the spatial relationship between anatomical structures.

Conclusions

To our knowledge, this is the first preliminary study to evaluate the role of MRI-based 3D pelvic models for investigating paraurethral masses. This is a feasible technique and may prove a useful addition to conventional 2D MRI. Further prospective studies are required to evaluate this modality for investigating such lesions and planning appropriate management.

     

Associations of total and free 25OHD and 1,25(OH)<Subscript>2</Subscript>D with serum markers of inflammation in older men

Summary

Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors.

Introduction

Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D.

Methods

We tested serum total 25OHD, total 1,25(OH)₂D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)₂D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study.

Results

IL-6 was lower in men with higher 25OHD (?0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) ?0.07 to ?0.38 μg/mL) and with higher 1,25(OH)₂D (?0.20 μg/mL, 95 % CI ?0.0004 to ?0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)₂D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)₂D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)₂D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)₂D).

Conclusions

Associations of 1,25(OH)₂D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)₂D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.

     

Conservative management of pelvic abscess following sacrocolpopexy: a report of three cases and review of the literature

Introduction and hypothesis

After sacrocolpopexy, intra-abdominal pelvic abscesses are often managed with intravenous antibiotics, excision of the mesh involved, and debridement of compromised tissue.

Methods and results

Three cases of successful management of pelvic abscesses after sacrocolpopexy using long-term antibiotics and percutaneous drainage of intra-abdominal abscesses without removing the mesh are presented.

Conclusions

In selected patients who have undergone sacrocolpopexy, with careful counseling, conservative management of pelvic abscesses with percutaneous drainage and long-term antibiotic treatment without the surgical excision of the mesh may play a role.

     

Failure of Expectations in Vaginal Surgery: Lack of Appropriate Consent,Goals and Expectations of Surgery

Introduction and Background

Vaginal surgery for the treatment of urinary stress incontinence (USI) and pelvic organ prolapse (POP) using a synthetic polypropylene mesh is going through a time of unprecedented turmoil and debate. This review focuses on vaginal surgery for vaginal prolapse and looks at the current scientific literature on issues surrounding surgery including consent and expectations.

Safety and Effectiveness of Surgical Options

Synthetic mesh has been used both abdominally and vaginally to improve the effectiveness of POP surgery. The relatively high incidence of mesh complications particularly with vaginal surgery has lead to repeat surgery, disappointment and litigation in some women. The benefits and risks of the various POP procedures are reviewed including native tissue repair, uterine conservation and obliterative vaginal surgery.

Conclusion

Women with symptomatic pelvic organ prolapse and their doctors have many treatment options. The benefits and risks should be discussed as part of shared decision making.

     

Informed consent checklists for midurethral slings: a common-sense approach

Introduction and Hypothesis

Following the US Food and Drug Administration’s (FDA’s) warning about the use of transvaginal mesh to treat pelvic organ prolapse (POP) and the use of single-incision slings to treat incontinence, the number of lawsuits for medical negligence regarding the use of any polypropylene mesh in the vagina has increased tremendously.

Methods

This same FDA document did not question the use of polypropylene midurethral slings and polypropylene for sacrocolpopexies. Surprisingly, despite all the evidence and recommendations from respected international scientific societies, we are constantly being called upon by our patients to defend the use of midurethral slings. The most common reasons for the new rash of medicolegal proceedings involving midurethral slings has to do with “breach of duties” resulting from undisclosed postoperative complications on the consent form and/or the lack of information in the medical records confirming that all possible alternative treatment options were presented to and discussed with the patient.

Results

One response to these lawsuits involves the addition of preoperative checklists when performing informed consent with patients electing surgical correction of stress urinary incontinence (SUI).

Conclusions

This clinical opinion provides an expert clinician’s perspectives and legal point of view on this controversial topic and discusses the role of a preoperative checklist supplementary to the standard informed consent form.

     

Effect of plasma NO<Subscript>x</Subscript> values on cardiac function in obese hypertensive and normotensive pediatric patients

Background

Hypertension (HT) is a major comorbidity of obesity that is associated with an increased risk of cardiovascular disease and higher mortality. The aim of our study was to evaluate cardiac function in obese hypertensive (OHT) and obese normotensive (ONT) pediatric patients and determine the effects of plasma nitric oxide (NO_x) values on cardiac function, while demonstrating the role of plasma NO_x in HT in obese pediatric patients.

Methods

The study population consisted of 62 patients (27 boys, 35 girls), aged 13–18 years and 21 age-matched healthy controls. All subjects enrolled in the study underwent echocardiography (Echo) evaluation and ambulatory blood pressure monitoring for HT. Plasma NO_x and biochemical values were studied in both patient groups separately.

Results

Plasma NO_x levels were found to be lower in the OHT group than in the ONT and control groups (p?<?0.001) and to be negatively correlated with left ventricular mass index values (p?<?0.05). Both the OHT and ONT groups had concentric hypertrophy of the heart.

Conclusions

Plasma NO_x plays an essential role in obesity-induced HT. Concentric hypertrophy of the left ventricle was found in both the OHT and ONT groups, indicating structural deformation of the heart.

     

Oral Vitamin B<Subscript>12</Subscript> Supplementation After Roux-en-Y Gastric Bypass: a Systematic Review

Background

Many respectable guidelines recommend lifelong vitamin B₁₂ injections for Roux-en-Y gastric bypass (RYGB) patients in the absence of lack of consensus on the efficacy of oral route of prophylaxis and the appropriate doses needed for this purpose. The purpose of this review was to examine the published English language scientific literature in accordance with PRISMA principles to find out if orally given vitamin B₁₂ is adequate for prophylactic purposes in RYGB patients and the appropriate dosages needed for this purpose if it is.

Methods

We examined the PubMed database for all English language articles examining various doses of oral vitamin B₁₂ supplementation after proximal RYGB in adult patients. The search revealed 19 such articles.

Results

The data suggest that oral vitamin B₁₂ supplementation doses of ≤?15 μg daily are insufficient to prevent deficiency in RYGB patients. Higher supplementation doses show better results and it appears that a dose of 600.0 μg vitamin B₁₂ daily is superior to 350.0 μg daily suggesting an incremental dose-response curve. It further appears that supplementation doses of 1000.0 μg vitamin B₁₂ daily lead to an increase in B₁₂ levels and are sufficient for the prevention of its deficiency in most RYGB patients.

Conclusion

The review finds that oral supplementation doses of ≤?15 μg vitamin B₁₂ daily are inadequate for prophylaxis of vitamin B₁₂ deficiency in adult RYGB patients but doses of 1000 μg vitamin B₁₂ daily might be adequate. Future studies need to examine this and even higher oral doses for vitamin B₁₂ supplementation for patients undergoing RYGB.

     

Implementing a Program of <Emphasis Type="Italic">Talimogene laherparepvec</Emphasis>

Background

Oncolytic viruses are genetically engineered or naturally occurring viruses that selectively replicate in cancer cells without harming normal cells. Talimogene laherparepvec (Imlygic^®), the first oncolytic viral therapy approved for treatment of cancer, was approved for treatment of locally advanced melanoma in October 2015.

Purpose

As a biologic product, use of T. laherparepvec in the clinical setting requires pretreatment planning and a unique systematic approach to deliver the therapy. The processes we describe herein could be adopted by other centers that choose to prescribe T. laherparepvec.

Methods

We studied our clinical trial experience with T. laherparepvec before we embarked on using commercially available T. laherparepvec. We created a standard operating procedure (SOP) with multidisciplinary buy-in and oversight from leadership in Infection Control at our institution. We reflected on clinical cases and the actual procedures of administering T. laherparepvec to create the SOP.

Results

The preimplementation planning, patient selection, identification of lesions to treat, the actual procedure, and ongoing assessment of patients are described. Tumoral-related factors that lead to unique challenges are described.

Conclusions

A process to ensure safe and responsible implementation of a program to administer T. laherparepvec for treatment of melanoma may improve the quality of treatment for patients who suffer from advanced melanoma.

     

Dynamic 3T pelvic floor magnetic resonance imaging in women progressing from the nulligravid to the primiparous state

Introduction and hypothesis

The objective was to prospectively characterize dynamic pelvic 3-Tesla magnetic resonance imaging (dp3T MRI) findings in nulligravida women and characterize changes 6 months after delivery in the same woman.

Methods

In this prospective study, nulligravida women seeking assisted reproductive technology for pregnancy were recruited. After physical examination by Pelvic Organ Prolapse Quantification (POP-Q), Brink assessment and measures including the Pelvic Floor Distress Inventory-20 and Pelvic Floor Impact Questionnaire-7, pre-pregnancy dp3T MRI at rest, with strain, and evacuation were performed. Assessments were repeated ≥6 months postpartum. Analysis included Welch and paired t tests for continuous variables, Fisher’s exact test for differences in categorical outcomes, and paired t tests for postpartum symptoms.

Results

Nineteen subjects (mean ± SD age, 31 ± 5 years) completed baseline clinical and dp3T MRI studies, 15 delivered and 10 (30.5 ± 3 years) completed pre-pregnancy and post-delivery clinical and dp3T MRI assessments. There were no significant changes in scores of validated questionnaires (all p > 0.05) or on POP-Q measures post-delivery. Two (20%) subjects without pre-pregnancy levator tears had tears on MRI post-delivery. MRI measures of pelvic organ descent were increased post-delivery. Seventeen pelvic soft-tissue parameters increased by greater than 10% post-delivery, including 5 out of 70 (7.1%), 17 out of 110 (15.5%), and 50 out of 110 (45.5%) values exceeding thresholds at rest, strain, and evacuation respectively.

Conclusions

Dynamic pelvic 3T MRI detected levator tears and increased pelvic organ descent, which can be directly attributed to pregnancy and delivery.

     

An innovative approach to treating vaginal mesh exposure after abdominal sacral colpopexy: endoscopic resection of mesh and platelet-rich plasma; initial experience in three women

Introduction and hypothesis

Polypropylene mesh exposure is uncommon after abdominal sacral colpopexy (ASC), but in case of symptomatic vaginal mesh exposure, surgery is needed. When treating it, care must be taken to completely remove the exposed mesh (EM), saving as much vaginal tissue as possible to avoid a subsequent shortened and narrowed vagina. In this video, we present a minimally invasive technique for treating EM after ASC using endoscopic mesh resection and autologous platelet-rich plasma (PRP) technology.

Methods

Three women were referred to our outpatient clinic for vaginal vault mesh exposure after laparoscopic ASC with concomitant hysterectomy. All women underwent endoscopic bipolar PlasmaKinetic resection (BPR) of EM, and PRP gel was delivered in the surgical site to cover the gap left by the resection.

Results

Mean operative time was 39.6 min. Surgery was uneventful in all cases. All women recovered sexual function, and nobody experienced relapsed pelvic organ prolapse at 1-year follow-up.

Conclusions

Our preliminary results show that BPR and PRP are safe, effective, and feasible for treating vaginal mesh exposure with conservation of anatomy and sexual function.

     

Comparison Between Different Intramuscular Vitamin B<Subscript>12</Subscript> Supplementation Regimes: a Retrospective Matched Cohort Study

Background

The incidence of vitamin B₁₂ deficiency after bariatric surgery can range from 26 to 70 %. There is no consensus on optimal vitamin B₁₂ supplementation in postbariatric patients. The objective of this study was to compare three different regimes.

Methods

In this retrospective matched cohort study, we included 63 patients with methylmalonic acid (MMA) levels ≥300 nmol/L. Group A (n?=?21) received 6 intramuscular (im) vitamin B₁₂ injections including a loading dose, group B (n?=?21) received 3 im vitamin B₁₂ injections without loading dose and group C (n?=?21) received no im vitamin B₁₂ injections.

Results

The total post-bariatric patient population consisted of 14 males (22.2 %) and 49 women (77.8 %) with a mean current body mass index of 30.6?±?8.0 kg/m². There was no significant difference in vitamin B₁₂ and MMA levels between 3 groups at baseline. There was a significant difference in follow-up vitamin B₁₂ levels of group A compared to group B (p?=?0.02) and group A compared to group C (p?=?0.03). In the follow-up results, there is also a significant decrease in MMA levels of group A compared to group B (p?=?0.02), group A compared to group C (p?<?0.001), and group B compared to group C (p?<?0.01).

Conclusions

In this study, a shorter injection regime is probably not sufficient to treat a vitamin B₁₂ deficiency. An injection regime with 6 injections recovered all vitamin B₁₂ deficiencies biochemically. MMA levels cannot recover spontaneously over time without additional im injection regime.

     

Ratio of lumbar 3-column osteotomy closure: patient-specific deformity characteristics and level of resection impact correction of truncal versus pelvic compensation

Purpose

The resection point of a lumbar three-column osteotomy (3CO) creates separation of the spino-pelvic complex. This study investigates the impact of patients’ baseline deformity and level of 3CO resection on the distribution of correction between the trunk and the pelvis following osteotomy closure.

Methods

Patients who underwent single lumbar 3CO, upper instrumented vertebra (UIV) T1–T10, and 6 month follow-up were included. The truncal and pelvic closures were calculated based on the vertebrae adjacent to the osteotomy level and the impact of radiographic parameters and level of 3CO on the closures were analyzed.

Results

113 patients were included. Patients who experienced more pelvic correction had significantly higher Pelvic Tilt and lower Sagittal Vertical Axis at baseline. Patients who underwent more caudal osteotomies with higher pelvic compensation with modest SVA sustained more pelvic correction.

Conclusions

The osteotomy closure is driven by patient’s specific deformity. More caudal osteotomy level leads to greater pelvic tilt improvement.Level of evidence: III

     

Endoscopic lithotripsy and vaginal excision of a calcified bladder-mesh extrusion

Introduction and hypothesis

Synthetic meshes have proven to increase efficacy of pelvic organ prolapse (POP) repair, but associated complications are not rare. Bladder mesh extrusion is one of the most serious adverse events following POP surgery with mesh. The aim of this video was to describe endoscopic and vaginal approaches for treating a bladder-mesh extrusion.

Methods

A 52-year-old female patient with a history of vaginal POP surgery with mesh was referred for severe pelvic and perineal pain, dyspareunia, and dysuria. She was found to have a bladder calculus on a mesh extrusion. The calculus was removed by endoscopic lithotripsy before vaginal mesh excision was performed.

Conclusions

With the use of synthetic vaginal mesh, the incidence of bladder-mesh extrusion could increase. This didactic video will be helpful to surgeons required to manage such cases using a minimally invasive treatment.

     

Pregnancy impact on uterosacral ligament and pelvic muscles using a 3D numerical and finite element model: preliminary results

Introduction and hypothesis

We studied the geometry of and changes in structures that play an important role in stabilizing the pelvic system during pregnancy using a numerical system at different gestational ages and postpartum.

Methods

We developed a parturient numerical model to assess pelvic structures at different gestational stages (16, 32, and 38 weeks) and postpartum (2 months and 1 year) using magnetic resonance imaging (MRI). Organs, muscles, and ligaments were segmented to generate a 3D model of the pelvis. We studied changes in the length of uterosacral ligaments (USL) and thickness of the puborectal portion of the levator ani muscle (LAM) during and after pregnancy. We used this model to perform finite element (FE) simulation and analyze deformations of these structures under stress from the increase in uterine weight.

Results

Analysis reveals an increase in the length of US ligaments at 16, 32, and 38 weeks. Two months after delivery, it decreases without returning to the length at 16 weeks of pregnancy. Similar changes were observed for the puborectal portion of the LAM. Variations observed in these structures are not equivalent to other anatomical structures of pelvic suspension. FE simulation with increased uterus weight does not lead to those findings.

Conclusion

This analysis brings new elements and a new focus for discussion relating to changes in pelvic balance of parturient women that are not simply linked to the increase in uterine volume.

     

Informed surgical consent for a mesh/graft-augmented vaginal repair of pelvic organ prolapse

Introduction and hypothesis

Complex issues surround informed surgical consent for pelvic reconstructive surgery.

Methods

Vaginally placed mesh/grafts are used with the intent to increase durability of the repair but potentially introduce unique complications, offering new challenges in informed surgical consent counseling.

Results

Informed consent is a process that takes place throughout the entire consultation with the patient. A written document often accompanies that process. This paper outlines necessary components of informed surgical consent and the theory behind each component.

Conclusions

We explore elements that should be included in the consent process with regard to expected benefits, alternatives, and material risks that are specific to the use of a mesh/graft-augmented vaginal repair of prolapse. Included is an appendix that may serve as a template for the creation of a surgeon’s own written informed consent document.

     

Heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABA<Subscript>A</Subscript>R-mediated depolarization

Objective

Children with repeated exposures to anesthesia at an early age are at an increased risk of cognitive impairment. Data in the literature link increased developmental depolarizing γ-aminobutyric acid (GABA) type A receptor (GABA_AR) at younger age to neurodevelopmental disorders. Here we investigated the involvement of GABAergic signaling during development in mediating the adverse effects of repeated sevoflurane exposures.

Methods

Sprague–Dawley male rats received repeated exposures to 3 % sevoflurane for 2 h daily for 3 consecutive days on postnatal days (P) 4, 5, and 6; maternally separated and unseparated rats served as controls. A subgroup of rats received three injections of the Na⁺–K⁺–2Cl^? cotransporter inhibitor, bumetanide (1.82 mg/kg, intraperitoneally) 15 min prior to initiation of each sevoflurane exposure.

Results

The results showed that repeated neonatal sevoflurane exposures contribute to learning and memory impairment in the Morris water maze (MWM) at P60. The corticosterone level was significantly increased immediately after repeated neonatal sevoflurane exposures. Repeated neonatal sevoflurane exposures heightened the secretion of corticosterone in response to stress in P7 and P60 rats. Pretreatment of male rats prior to each sevoflurane exposure with bumetanide attenuated the corticosterone level immediately after repeated neonatal sevoflurane exposures, normalized endocrine response to stress at P7 and P60, and attenuated the sevoflurane-induced learning and memory impairment in the MWM.

Conclusion

These data suggested that the heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABA_AR-mediated depolarization.

     

Broadband near-infrared spectroscopy can detect cyanide-induced cytochrome aa<Subscript>3</Subscript> inhibition in rats: a proof of concept study

Purpose

Clinically available near-infrared spectroscopy (NIRS) devices use two to five wavelengths of light to measure the relative amounts of oxyhemoglobin and deoxyhemoglobin in tissue to determine tissue hemoglobin oxygen saturation (StO₂). In addition to StO₂, broadband NIRS devices (using hundreds of wavelengths of light) may be able to measure the oxidation state of mitochondrial cytochrome aa₃ (Cyt_ox) which reflects the subcellular energetic state. We hypothesize that broadband NIRS devices can measure Cyt_ox independent of changes in hemoglobin saturation.

Methods

In this prospective non-randomized study, 20 male Sprague-Dawley rats (300 g) were anesthetized with isoflurane, tracheally intubated, and ventilated with 100% O₂ containing 2% isoflurane. They were subsequently instrumented with a broadband NIRS device that used a halogen light source coupled to an emitting fibreoptic cable. Three receiving fibreoptic cables were utilized; one analyzed the light source and the other two were directed at the base of the skull. Each receiving fibre was connected to a spectrometer to measure light intensity. Sodium cyanide (NaCN) 5 mg·kg^?1 iv was injected in order to produce cytochrome aa₃ reduction. Two to three minutes after injection, oxygen was eliminated and 100% nitrogen (i.e., anoxia) was used for ventilation in order to induce a reduction in both cytochrome aa₃ and hemoglobin desaturation. Changes in the cytochrome oxidation state and hemoglobin oxygenation were calculated using a broadband algorithm and compared before and after both the NaCN and anoxia interventions.

Results

The NaCN injection resulted in a decrease in median [interquartile range (IQR)] deoxyhemoglobin (?0.014 [?0.29 to ?0.005] arbitrary units [AU]; P < 0.001), an increase in oxyhemoglobin (0.013 [?0.011 to 0.031] AU; P < 0.001), and a reduction in cytochrome aa₃ (?0.015 [?0.020 to ?0.011] AU; P < 0.001). Anoxia resulted in an increase in median [IQR] deoxyhemoglobin (0.13 [0.11 to 0.18] AU; P < 0.001), a decrease in oxyhemoglobin (?0.17 [?0.22 to ?0.15] AU; P < 0.001), and a reduction in cytochrome aa₃ (?0.04 [?0.06 to ?0.03] AU; P < 0.001).

Conclusion

Broadband NIRS can effectively measure the directionality of changes in both Cyt_ox and StO₂ by uncoupling the cytochrome and hemoglobin signals through inhibition of the electron transport chain and anoxia.