The Effect of Preoperative Fiber on Postoperative Bowel Function After Pelvic Reconstructive Surgery: A Randomized Controlled Trial.

IMPORTANCE: There are limited studies evaluating the effect of preoperative interventions on postoperative bowel function after prolapse surgery. OBJECTIVE: The objective of this study was to evaluate if preoperative fiber intake reduces time to first bowel movement after surgery for pelvic organ prolapse. STUDY DESIGN: We performed a randomized controlled trial of women undergoing pelvic organ prolapse surgery between July 2019 and May 2021. Participants were recruited at their preoperative visit and randomized to receive either 3.4 g psyllium fiber supplementation twice a day for 1 week before surgery or no fiber supplementation before surgery. Postoperative bowel regimen was standardized for both groups. Participants completed a bowel diary for their first postoperative bowel movement after surgery characterized by the Bristol Stool Scale and any associated pain or urgency. The primary outcome was time to first bowel movement. Secondary outcomes included pain associated with first bowel movement. RESULTS: Eighty-four patients were enrolled in the study. Seventy-one patients had complete data for primary analysis, with 35 patients in the intervention group and 36 patients in the control group. Demographic and perioperative characteristics were similar between the groups. There was no difference found between the groups with respect to time to first bowel movement (control: 68.3 [SD, 25] hours vs intervention: 66.5 [SD, 23] hours, P = 0.749). There was no difference found with pain associated with first bowel movement (visual analog scale median [interquartile range] control: 2.0 [0.0-4.0] vs intervention: 2.0 [1.0-4.0]; P = 0.655). CONCLUSIONS: Preoperative fiber supplementation before prolapse surgery does not improve time to first bowel movement after surgery.

Risk factors for explantation due to infection after sacral neuromodulation: a multicenter retrospective case-control study.

BACKGROUND: Sacral neuromodulation is an effective therapy for overactive bladder, urinary retention, and fecal incontinence. Infection after sacral neurostimulation is costly and burdensome. Determining optimal perioperative management strategies to reduce the risk of infection is important to reduce this burden. OBJECTIVE: We sought to identify risk factors associated with sacral neurostimulator infection requiring explantation, to estimate the incidence of infection requiring explantation, and identify associated microbial pathogens. STUDY DESIGN: This is a multicenter retrospective case-control study of sacral neuromodulation procedures completed from Jan. 1, 2004, through Dec. 31, 2014. We identified all sacral neuromodulation implantable pulse generator implants as well as explants due to infection at 8 participating institutions. Cases were patients who required implantable pulse generator explantation for infection during the review period. Cases were included if age ≥18 years old, follow-up data were available ≥30 days after implantable pulse generator implant, and the implant was performed at the institution performing the explant. Two controls were matched to each case. These controls were the patients who had an implantable pulse generator implanted by the same surgeon immediately preceding and immediately following the identified case who met inclusion criteria. Controls were included if age ≥18 years old, no infection after implantable pulse generator implant, follow-up data were available ≥180 days after implant, and no explant for any reason <180 days from implant. Controls may have had an explant for reasons other than infection at >180 days after implant. Fisher exact test (for categorical variables) and Student t test (for continuous variables) were used to test the strength of the association between infection and patient and surgery characteristics. Significant variables were then considered in a multivariable logistic regression model to determine risk factors independently associated with infection. RESULTS: Over a 10-year period at 8 academic institutions, 1930 sacral neuromodulator implants were performed by 17 surgeons. In all, 38 cases requiring device explant for infection and 72 corresponding controls were identified. The incidence of infection requiring explant was 1.97%. Hematoma formation (13% cases, 0% controls; P = .004) and pocket depth of ≥3 cm (21% cases, 0% controls; P = .031) were independently associated with an increased risk of infection requiring explant. On multivariable regression analysis controlling for significant variables, both hematoma formation (P = .006) and pocket depth ≥3 cm (P = .020, odds ratio 3.26; 95% confidence interval, 1.20-8.89) remained significantly associated with infection requiring explant. Of the 38 cases requiring explant, 32 had cultures collected and 24 had positive cultures. All 5 cases with a hematoma had a positive culture (100%). Of the 4 cases with a pocket depth ≥3 cm, 2 had positive cultures, 1 had negative cultures, and 1 had a missing culture result. The most common organism identified was methicillin-resistant Staphylococcus aureus (38%). CONCLUSION: Infection after sacral neuromodulation requiring device explant is low. The most common infectious pathogen identified was methicillin-resistant S aureus. Demographic and health characteristics did not predict risk of explant due to infection, however, having a postoperative hematoma or a deep pocket ≥3 cm significantly increased the risk of explant due to infection. These findings highlight the importance of meticulous hemostasis as well as ensuring the pocket depth is <3 cm at the time of device implant.

Barriers and Challenges to Treatment Alternatives for Early-Stage Cervical Cancer in Lower-Resource Settings.

Cervical cancer is one of the most common cancers among women worldwide, and approximately 85% of new diagnoses occur in less-developed regions of the world. Global efforts in cervical cancer to date have focused on primary and secondary prevention strategies of human papillomavirus vaccination and cervical cancer screening. Cervical cancer screening is effective to reduce the incidence of cervical cancer and can result in diagnosis at earlier stages, but it will take time to realize its full impact. With expansion of screening programs, there is now a greater imperative to increase access to treatment for women who have cervical cancer, particularly in earlier stages of disease, when it is still curable. Resources for multimodality treatment can be limited-or even absent-in many less-developed regions of the world and may be associated with geographic, social, and financial barriers for the patient. However, there is evidence that, in many cases, less-invasive and less-resource-intensive treatment options are still effective. To this end, the National Comprehensive Cancer Network and American Society of Clinical Oncology have published guideline adaptations for specific resource constraints, and research about more conservative approaches to the treatment of cervical cancer continues. This review focuses on potential barriers and challenges to provision of safe and effective treatment of early-stage cervical cancer in lower-resource settings, and it suggests future directions for expansion of access to cervical cancer treatment around the world.

Structural and functional analysis of g protein-coupled receptor kinase inhibition by paroxetine and a rationally designed analog.

Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2) that improves cardiac performance in live animals. Paroxetine exhibits up to 50-fold selectivity for GRK2 versus other GRKs. A better understanding of the molecular basis of this selectivity is important for the development of even more selective and potent small molecule therapeutics and chemical genetic probes. We first sought to understand the molecular mechanisms underlying paroxetine selectivity among GRKs. We directly measured the K(D) for paroxetine and assessed its mechanism of inhibition for each of the GRK subfamilies and then determined the atomic structure of its complex with GRK1, the most weakly inhibited GRK tested. Our results suggest that the selectivity of paroxetine for GRK2 largely reflects its lower affinity for adenine nucleotides. Thus, stabilization of off-pathway conformational states unique to GRK2 will likely be key for the development of even more selective inhibitors. Next, we designed a benzolactam derivative of paroxetine that has optimized interactions with the hinge of the GRK2 kinase domain. The crystal structure of this compound in complex with GRK2 confirmed the predicted interactions. Although the benzolactam derivative did not significantly alter potency of inhibition among GRKs, it exhibited 20-fold lower inhibition of serotonin reuptake. However, there was an associated increase in the potency for inhibition of other AGC kinases, suggesting that the unconventional hydrogen bond formed by the benzodioxole ring of paroxetine is better accommodated by GRKs.

Effect of a single course of isotretinoin therapy on bone mineral density in adolescent patients with severe, recalcitrant, nodular acne.

BACKGROUND: Adverse changes in bone have been reported for patients undergoing high-dose, long-term (several years) isotretinoin therapy for disorders of cornification. The effect of short-term (4-5 months) therapy at the lower dose recommended for acne on bone development in younger, growing adolescent (12-17 years) patients has not been well studied. OBJECTIVE: The purpose of the study was to evaluate the effect of a standard, single course of isotretinoin (Accutane) therapy on bone mineral density (BMD) of the lumbar spine and hip in adolescents ages 12 to 17 years with severe, recalcitrant, nodular acne. METHODS: In this open-label, multicenter study, 217 adolescents (81 girls) with severe, recalcitrant, nodular acne were enrolled and treated with isotretinoin twice daily with food at the recommended total dose of approximately 1 mg/kg for 16 to 20 weeks. BMD in the lumbar spine and hip was measured at baseline and at the end of therapy by dual energy radiograph absorptiometry. RESULTS: There was no clinically significant mean change in BMD measured at the lumbar spine (+1.4%, range: -4.9% to +12.3%) or total hip (-0.26%, range: -11.3% to +15.0%). Hyperostosis was not observed in any patient. Typical efficacy expected in the treatment of acne was observed. CONCLUSIONS: A 16- to 20-week course of isotretinoin treatment at the recommended dose for severe acne has no clinically significant effect on lumbar spine and total hip BMD in the adolescent (12-17 years) population.