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November 2023

Recent Research Publications- November 2023

Caprini Model Integration into an Electronic Medical Record to Improve Perioperative Venous Thromboembolism Prophylaxis.

Akella S, Russo D, Bradley CS, Kowalski JT.

Obstet Gynecol. 2023 Oct 5. doi: 10.1097/AOG.0000000000005390. Epub ahead of print. PMID: 37797334.

This quality-improvement retrospective cohort study of patients undergoing major elective nononcologic gynecologic surgery compares the proportion of patients receiving appropriate perioperative venous thromboembolism (VTE) chemoprophylaxis before and after a novel integration of the Caprini risk-assessment model (RAM) into the electronic medical record (EMR). A sample size of 83 patients in each group (166 total) was calculated to provide 80% power and show a 20% increase in appropriate administration of VTE prophylaxis, with an alpha of 0.05. Heparin was appropriately used in 24 patients (28.9%) in the pre-Caprini-RAM group and 39 patients (47.0%) in the post-Caprini-RAM group (P=.016). There were no differences in bleeding events, transfusions, or other secondary outcomes. Integrating the Caprini-RAM into an EMR for patients undergoing nononcologic gynecologic surgery significantly improved appropriate use of VTE chemoprophylaxis.

Reply By Authors.

Mawla I, Schrepf A, Kutch JJ, Helmuth ME, Smith AR, Ichesco E, Yang CC, Andreev VP, Kreder KJ, Bradley CS, Magnotta VA, Kirkali Z, Harris RE, Lai HH, Harte SE.

J Urol. 2023 Oct 5:101097JU000000000000369902. doi: 10.1097/JU.0000000000003699.02. Epub ahead of print. PMID: 37796787.

Naturalistic Bladder Filling Reveals Subtypes in Overactive Bladder Syndrome That Differentially Engages Urinary Urgency-Related Brain Circuits: Results From the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN)

Mawla I, Schrepf A, Kutch JJ, Helmuth ME, Smith AR, Ichesco E, Yang CC, Andreev VP, Kreder KJ, Bradley CS, Magnotta VA, Kirkali Z, Harris RE, Lai HH, Harte SE.

J Urol. 2023 Oct 5:101097JU0000000000003699. doi: 10.1097/JU.0000000000003699. Epub ahead of print. PMID: 37796776.

Purpose: Overactive bladder (OAB) may be attributed to dysfunction in supraspinal brain circuits. Overactive bladder participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study reported sensations of urinary urgency during a bladder-filling paradigm while undergoing brain functional MRI to map supraspinal dysfunction.

Materials and methods: OAB participants and controls (CONs) completed 2 resting-state functional MRI scans following consumption of 350 mL water. Scans were conducted at fuller and emptier bladder states, interleaved with voiding. Urgency ratings (0-10) were assessed. Patterns of urgency during bladder filling were investigated using latent class trajectory models. Clusters of participants encompassing each pattern (ie, subtype) were derived from aggregated groups of OAB and CON independent of diagnosis.

Results: Two distinct patterns of urgency trajectories were revealed: first subtype with OAB and CON who were unresponsive to bladder filling (OAB-1 and CON-1) and second highly responsive subtype predominantly containing OAB (OAB-2). OAB-2 participants scored significantly higher on urinary symptoms but not pain or psychosocial measures. Neuroimaging analyses showed change in urgency due to both bladder filling and voided volume related to multiple loci of brain network connectivity in OAB-2, and in some cases, different than OAB-1 and/or CON-1. Sensorimotor to dorsomedial/dorsolateral prefrontal connectivity mediated the relationship between stimulus (voided volume) and percept (urgency) in OAB-2.

Conclusions: Our results reveal different OAB subtypes with latent class trajectory models of urgency ratings during natural bladder filling. Functional MRI revealed differences in pathophysiology between subtypes, namely sensorimotor-prefrontal connectivity is a key locus in OAB patients with higher urinary symptoms.

Impact of Sling at Time of Prolapse Surgery on Overactive Bladder.

Kowalski JT, Maetzold E, Kenne KA, Bradley CS.

Urogynecology (Phila). 2023 Sep 20. doi: 10.1097/SPV.0000000000001411. Epub ahead of print. PMID: 37737833.

Importance: Prolapse surgery and sling surgery both lead to improvement in overactive bladder. However, less is known regarding how slings performed concurrently with less is know about how overactive bladder symptoms change in patients having prolapse surgery with a sling compared to prolapse surgery without a sling.

  • The primary aim was to compare change in postoperative overactive bladder symptoms in patients with preoperative overactive bladder who underwent sling placement versus no sling with prolapse surgery.

Study design: This was a secondary analysis of a cohort study evaluating overactive bladder in patients undergoing prolapse surgery. Sling procedures were performed concomitantly for treatment or prevention of stress incontinence. Baseline and 3-month follow-up urinary symptoms were assessed with the Overactive Bladder Questionnaire Short Form (OAB-q SF) and Urinary Distress Inventory-6 (UDI-6).

  • Of patients with overactive bladder, 26 (40.0%) underwent midurethral sling (MUS) placement and 39 (60.0%) no sling. Preoperative OAB-q SF bother (score [SD], 46.8 [20.2] vs 40.2 [22.1]; P = 0.23) was similar between groups, but UDI-6 scores (59.2 [28.8] vs 43.8 [29.1]; P = 0.04) were higher in the sling group. At 3 months, the change (improvement) in OABq-SF bother (-16.9 [24.1] vs -22.4 [23.0]; P = 0.36), OABq-SF health-related quality of life (22.8 [28.6] vs 22.9 [23.9]; P = 0.99), and UDI-6 (-38.8 [32.9] vs -34.0 [27.8]; P = 0.53) were similar in the MUS and no MUS groups.

Conclusion: Patients with prolapse and overactive bladder undergoing prolapse surgery with a sling had similar improvements in OAB-q SF bother scores compared with those who did not have a sling.

Twelve Month Outcomes of Pelvic Organ Prolapse Surgery in Patients With Uterovaginal or Posthysterectomy Vaginal Prolapse Enrolled in the Multicenter Pelvic Floor Disorders Registry.

Ferrando CA, Bradley CS, Meyn LA, Brown HW, Moalli PA, Heisler CA, Murarka SM, Foster RT Sr, Chung DE, Whitcomb EL, Gutman RE, Andy UU, Shippey SH, Anger J, Yurteri-Kaplan LA.

Urogynecology (Phila). 2023 Oct 1;29(10):787-799. doi: 10.1097/SPV.0000000000001410. PMID: 37733440.

Objective: The aim of the study was to compare 12-month subjective and objective outcomes between 3 approaches to apical pelvic organ prolapse (POP) surgery in patients presenting with uterovaginal or posthysterectomy vaginal prolapse enrolled in the Pelvic Floor Disorders Registry for Research.

Study design: This was an analysis of a multicenter, prospective registry that collected both patient- and physician-reported data for up to 3 years after conservative (pessary) and surgical treatment for POP. Twelve-month subjective and anatomic outcomes for patients who underwent surgical treatment were extracted from the registry for analysis. Pelvic organ prolapse recurrence was defined as a composite outcome and compared between the 3 apical surgery groups (native tissue repair, sacrocolpopexy, colpocleisis) as well as the 2 reconstructive surgery groups (native tissue repair and sacrocolpopexy).

  • A total of 1,153 women were enrolled in the registry and 777 (67%) opted for surgical treatment, of whom 641 underwent apical repair and were included in this analysis (404 native tissue repair, 187 sacrocolpopexy, and 50 colpocleisis). The overall incidence of recurrence was as follows: subjective 6.5%, anatomic 4.7%, retreatment 7.2%, and composite 13.6%. The incidence of recurrence was not different between the 3 surgical groups. When baseline patient characteristics were controlled for, composite POP recurrence between the native tissue and sacrocolpopexy groups remained statistically nonsignificant. Concurrent perineorrhaphy with any type of apical POP surgery was associated with a lower risk of recurrence (adjusted odds ratio, 0.43; 95% confidence interval, 0.25-0.74; P = 0.002) and prior hysterectomy was associated with a higher risk (adjusted odds ratio, 1.77, 95% confidence interval, 1.04-3.03; P = 0.036).

Conclusion: Pelvic Floor Disorders Registry for Research participants undergoing native tissue apical POP repair, sacrocolpopexy, and colpocleisis surgery had similar rates of POP recurrence 12 months after surgery.

Anti-angiogenic mechanisms and serotonergic dysfunction in the Rgs2 knockout model for the study of psycho-obstetric risk.

Gumusoglu SB, Kiel MD, Gugel A, Schickling BM, Weaver KR, Lauffer MC, Sullivan HR, Coulter KJ, Blaine BM, Kamal M, Zhang Y, Devor EJ, Santillan DA, Gantz SC, Santillan MK.

Neuropsychopharmacology. 2023 Oct 17. doi: 10.1038/s41386-023-01749-3. Epub ahead of print. PMID: 37848733.

Psychiatric and obstetric diseases are growing threats to public health and share high rates of co-morbidity. G protein-coupled receptor signaling (e.g., vasopressin, serotonin) may be a convergent psycho-obstetric risk mechanism. Regulator of G Protein Signaling 2 (RGS2) mutations increase risk for both the gestational disease preeclampsia and for depression. We previously found preeclampsia-like, anti-angiogenic obstetric phenotypes with reduced placental Rgs2 expression in mice. Here, we extend this to test whether conserved cerebrovascular and serotonergic mechanisms are also associated with risk for neurobiological phenotypes in the Rgs2 KO mouse. Rgs2 KO exhibited anxiety-, depression-, and hedonic-like behaviors. Cortical vascular density and vessel length decreased in Rgs2 KO; cortical and white matter thickness and cell densities were unchanged. In Rgs2 KO, serotonergic gene expression was sex-specifically changed (e.g., cortical Htr2a, Maoa increased in females but all serotonin targets unchanged or decreased in males); redox-related expression increased in paraventricular nucleus and aorta; and angiogenic gene expression was changed in male but not female cortex. Whole-cell recordings from dorsal raphe serotonin neurons revealed altered 5-HT1A receptor-dependent inhibitory postsynaptic currents (5-HT1A-IPSCs) in female but not male KO neurons. Additionally, serotonin transporter blockade by the SSRI sertraline increased the amplitude and time-to-peak of 5-HT1A-IPSCs in KO neurons to a greater extent than in WT neurons in females only. These results demonstrate behavioral, cerebrovascular, and sertraline hypersensitivity phenotypes in Rgs2 KOs, some of which are sex-specific. Disruptions may be driven by vascular and cell stress mechanisms linking the shared pathogenesis of psychiatric and obstetric disease to reveal future targets.

International urogynecological consultation chapter 4.1: definition of outcomes for pelvic organ prolapse surgery.

Kowalski JT, Barber MD, Klerkx WM, Grzybowska ME, Toozs-Hobson P, Rogers RG, Milani AL.

Int Urogynecol J. 2023 Oct 11. doi: 10.1007/s00192-023-05660-9. Epub ahead of print. PMID: 37819369.

Introduction and hypothesis: This manuscript of Chapter 4 of the International Urogynecological Consultation (IUC) on Pelvic Organ Prolapse (POP) reviews the literature and makes recommendations on the definition of success in the surgical treatment of pelvic organ prolapse.

Methods: An international group containing seven urogynecologists performed an exhaustive search of the literature using two PubMed searches and using PICO methodology. The first search was from 01/01/2012-06/12/2022. A second search from inception to 7/24/2022 was done to access older references. Publications were eliminated if not relevant to the clinical definition of surgical success for the treatment of POP. All abstracts were reviewed for inclusion and any disagreements were adjudicated by majority consensus of the writing group. The resulting list of articles were used to inform a comprehensive review and creation of the definition of success in the surgical treatment of POP.

Outcomes: The original search yielded 12,161 references of which 45 were used by the writing group. Ultimately, 68 references are included in the manuscript. For research purposes, surgical success should be primarily defined by the absence of bothersome patient bulge symptoms or retreatment for POP and a time frame of at least 12 months follow-up should be used. Secondary outcomes, including anatomic measures of POP and related pelvic floor symptoms, should not contribute to a definition of success or failure. For clinical practice, surgical success should primarily be defined as the absence of bothersome patient bulge symptoms. Surgeons may consider using PASS (patient acceptable symptom state) or patient goal attainment assessments, and patients should be followed for a minimum of at least one encounter at 6-12 weeks post-operatively. For surgeries involving mesh longer-term follow-up is recommended.

Trichomoniasis {book chapter}

Munzy CA, Stockdale CK, Kissinger PJ.

In: De Seat F, Vieira Baptista P, editors. Infections in gynecology, Gynecology Module Volume 12, The Continuous Textbook of Women’s Medicine Series. GLOWM: The Alliance for Global Women’s Medicine; 2023 August. ISSN 1756-2228; doi:103843/GLOWM.419923.