A Prospective Study of Bladder Function Following Endometriosis Surgery With Up to Eight years Follow-up.

STUDY OBJECTIVE: To assess long-term urinary function for women having laparoscopic surgery for endometriosis. DESIGN: Institutional Review Board-approved nested cohort study within a larger randomized controlled trial assessing urinary function following any benign laparoscopy for gynecological presentations. SETTING: Two tertiary-level university-affiliated hospitals. PATIENTS: Women with histologically confirmed endometriosis within the randomized controlled trial between April 2012 and November 2019, where baseline urinary function was determined. INTERVENTIONS: Women with histologically confirmed endometriosis were contacted between February and October 2020, and urinary function was re-assessed. MEASUREMENTS AND MAIN RESULTS: Urinary function was assessed using validated questionnaires across the domains of filling, voiding, incontinence, and quality of life determined distant from surgery. Higher scores correlated with a greater severity of symptoms. From 518/711 (72.9%) women with histologically confirmed endometriosis, 289/518 (55.8%) consented to the nested study. At a mean of 50 months (range 12-103 months) post-operatively, 35 participants (12.1%) had sought treatment for bladder symptoms, and 81 participants (28.0%) reported at least one urinary tract infection since their index surgery. There was a significant worsening of symptoms for filling, voiding, incontinence, and quality of life pre-operative to post-operatively (2.27 vs 3.32, 0.93 vs 2.02, 1.06 vs 2.32, 0.83 vs 2.13 respectively, p <.001). There was no statistically significant difference in urinary questionnaire scores in participants with and without uterovesical endometriosis. There was no statistically significant difference in any parameter when comparing any revised American Society of Reproductive Medicine (rASM) stage of endometriosis. Participants who had post-operative urinary retention reported a higher mean voiding score than those who did not (3.24 vs 1.94, p = .017), while participants with post-operative urinary tract infection reported a higher mean frequency score than those who did not (5.17 vs 3.24, p = .016). CONCLUSION: This study suggests a decline in urinary function over time following laparoscopic surgery for endometriosis that is not dependent on the severity or location of the disease.

Commissioning of Mobius3D/FX for patient-specific quality assurance: The CUIMC-NewYork Presbyterian Hospital experience.

PURPOSE: To present the process undertaken by our institute in commissioning Mobius3D (M3D) for patient-specific quality assurance. METHOD: 168 plans were randomly selected to compare dose distribution measured with ArcCheck and dose calculated from M3D, both compared against the treatment planning system (TPS). The gamma criteria for measurement and M3D are 3%/2 mm with 10% and 50% dose thresholds, respectively. The effect of tissue inhomogeneity was investigated on 11 plans by recalculating the dose in M3D on a homogeneous phantom. Tolerance and action limits were established following the AAPM Task Group 218 recommendations. RESULTS: The M3D showed high variability in gamma passing rate compared to the measurement. Twenty-three out of 168 plans had false negative dose comparisons. These plans fall under high tissue inhomogeneity like lung and metal implants, small field targets, and breast plans planned with high energy. One false negative case (0.6%) was observed. A single tolerance limit of 91% and 92% gamma passing rate for the M3D and measurement-based PSQA were established, respectively. Against the expectation, recalculating plans on the homogeneous phantom in M3D did not necessarily increase the gamma passing rate. These plans have a duty cycle >4.2, and the small field sizes combined with differences in slice thickness contributed to observed dose differences in the homogeneous phantom comparisons. CONCLUSION: Following the commissioning, M3D is adopted in our institute. Currently, the gamma criteria used for measurement and M3D are 3%/2 mm, 40% dose threshold, with gamma passing rates of 92% and 95%, respectively. A higher passing rate for M3D is adopted until more data is available. The combined effect of plan modulation, the field sizes, the tissue inhomogeneity, the dose algorithm, and the volume averaging effect from differences in slice thickness can contribute to the differences in dose in M3D and TPS.

MU variability in CBCT-guided online adaptive radiation therapy.

PURPOSE: CBCT-guided online-adaptive radiotherapy (oART) systems have been made possible by using artificial intelligence and automation to substantially reduce treatment planning time during on-couch adaptive sessions. Evaluating plans generated during an adaptive session presents significant challenges to the clinical team as the planning process gets compressed into a shorter window than offline planning. We identified MU variations up to 30% difference between the adaptive plan and the reference plan in several oART sessions that caused the clinical team to question the accuracy of the oART dose calculation. We investigated the cause of MU variation and the overall accuracy of the dose delivered when MU variations appear unnecessarily large. METHODS: Dosimetric and adaptive plan data from 604 adaptive sessions of 19 patients undergoing CBCT-guided oART were collected. The analysis included total MU per fraction, planning target volume (PTV) and organs at risk (OAR) volumes, changes in PTV-OAR overlap, and DVH curves. Sessions with MU greater than two standard deviations from the mean were reoptimized offline, verified by an independent calculation system, and measured using a detector array. RESULTS: MU variations relative to the reference plan were normally distributed with a mean of -1.0% and a standard deviation of 11.0%. No significant correlation was found between MU variation and anatomic changes. Offline reoptimization did not reliably reproduce either reference or on-couch total MUs, suggesting that stochastic effects within the oART optimizer are likely causing the variations. Independent dose calculation and detector array measurements resulted in acceptable agreement with the planned dose. CONCLUSIONS: MU variations observed between oART plans were not caused by any errors within the oART workflow. Providers should refrain from using MU variability as a way to express their confidence in the treatment planning accuracy. Clinical decisions during on-couch adaptive sessions should rely on validated secondary dose calculations to ensure optimal plan selection.

Vaginal epithelial histology before and after fractional CO2 laser in postmenopausal women: a double-blind, sham-controlled randomized trial.

BACKGROUND: Postmenopausal vaginal symptoms affect over 60% of women and may substantially impact a woman's quality of life. Since 2012, fractional CO2 laser has been suggested as a treatment for this indication. Structural assessment of vaginal epithelium using microscopic biopsy examination has been used as a primary outcome measure and surrogate determinant of success of vaginal laser in previous clinical studies. OBJECTIVE: This study aimed to report the effects of laser compared with sham treatment on human vaginal epithelium from postmenopausal women using microscopic examination of tissue biopsies. STUDY DESIGN: This single-center double-blind, sham-controlled randomized controlled trial was performed in a tertiary hospital in Sydney, Australia. A total of 49 postmenopausal women who were symptomatic of at least 1 vaginal symptom (vaginal dryness, burning, itching; dyspareunia; or dryness) were randomized to either laser or sham treatment. For this nested histologic study, participants had a pre- and post-treatment vaginal wall biopsy collected. Biopsy samples were analyzed by 3 independent specialist gynecologic pathologists and categorized as Type 1 (well-estrogenized), 2 (poorly estrogenized), or 3 (combination) mucosae. Other outcomes assessed included symptom severity (visual analog scale for symptoms including most bothersome symptom, and Vulvovaginal Symptom Questionnaire) and Vaginal Health Index. Prespecified secondary analyses of data were performed. Categorical data were analyzed using the Pearson chi-square test (or Fisher exact test if <5 in any category) or related-samples McNemar test for paired nonparametric data. Nonparametric, continuous variables were assessed using Wilcoxon signed-rank test or Mann-Whitney U test, and parametric variables with t test or 1-way analysis of variance as appropriate. All analyses were performed using SPSS software version 26.0 (IBM Corp, Armonk, NY). RESULTS: There was no significant difference in microscopic features of vaginal epithelium following laser or sham treatment (P=.20). Further subgroup analyses of age, menopause type, duration of reproductive life, time since menopause and BMI, still demonstrated no significant difference between laser and sham groups in histological category of vaginal epithelium. Microscopic features at pre-treatment vaginal biopsy were Type 1 in 27% (13/49). There was no significant difference in VAS score for overall vaginal symptom between those classified as Type 1 vs. Type 2/3 (VAS score overall: Type 1 vs. Type 2/3, (48.1 [95% CI 27.0, 69.2] vs. 61.5 [95% CI 49.8, 73.3]; P=.166). CONCLUSION: Data from this double-blind, sham-controlled randomized controlled trial demonstrate that fractional CO2 laser and sham treatment have a comparable histologic effect on vaginal tissue that is not significantly different. Fractional CO2 laser is not significantly different from sham treatment and should not be recommended for clinical use for postmenopausal vaginal symptoms.

Immediate versus delayed urinary catheter removal following non-hysterectomy benign gynaecological laparoscopy: a randomised trial.

OBJECTIVE: To compare rates of urinary retention and postoperative urinary tract infection between women with immediate versus women with delayed removal of indwelling catheter following benign non-hysterectomy gynaecological laparoscopic surgery. DESIGN: This randomised clinical trial was conducted between February 2012 and December 2019, with follow-up to 6 weeks. SETTING: Two university-affiliated teaching hospitals in Sydney, Australia. POPULATION: Study participants were 693 women aged 18 years or over, undergoing non-hysterectomy laparoscopy for benign gynaecological conditions, excluding pelvic floor or concomitant bowel surgery. METHODS: Three hundred and fifty-five participants were randomised to immediate removal of urinary catheter and 338 participants were randomised to delayed removal of urinary catheter. MAIN OUTCOME MEASURES: The co-primary outcomes were urinary retention and urinary tract infection. Secondary outcomes included hospital readmission, analgesia requirements, duration of hospitalisation and validated bladder function questionnaires. RESULTS: Urinary retention was higher after immediate compared with delayed removal of the urinary catheter (8.2% vs 4.2%, RR 1.8, 95% CI 1.0-3.0, p = 0.04). Although urinary tract infection was 7.2% following delayed removal of the urinary catheter and 4.7% following immediate removal of the urinary catheter, the difference was not statistically significant (RR 0.7, 95% CI 0.3-1.2, p = 0.2). CONCLUSIONS: There is an increased risk of urinary retention with the immediate compared with the delayed removal of the urinary catheter following benign non-hysterectomy gynaecological laparoscopic surgery. The difference in urinary tract infection was not significant. There is 1/12 risk of re-catheterisation after immediate urinary catheter removal. It is important to ensure that patients report normal voiding and emptying prior to discharge, to reduce the need for readmission for the management of urinary retention.

Probiotic Bifidobacterium lactis Probio-M8 treated and prevented acute RTI, reduced antibiotic use and hospital stay in hospitalized young children: a randomized, double-blind, placebo-controlled study.

PURPOSE: The development of probiotics has seen tremendous growth over the years, with health benefits ranging from gut health to respiratory. We thus aimed to investigate the effects of probiotic Bifidobacterium lactis Probio-M8 (2 × 1010 log CFU/day) against acute respiratory tract infections (RTI), use of antibiotics, hospitalization period and elucidate the possible mechanisms of action in hospitalized young children. METHOD: A prospective, randomized, double-blind and placebo-controlled study was performed in RTI-hospitalized children. Patients were randomized to either the probiotic (n = 60, mean age 13.81 ± 0.90 months) or placebo (n = 60, mean age 12.11 ± 0.73 months) which were administered upon admission, continued during hospitalization and 4-week post-discharged. RTI and gut health parameters were assessed at these time points using validated questionnaires while concentrations of inflammatory cytokines were assessed via oral swabs. RESULTS: Probio-M8 reduced the duration of nasal, pharyngeal and general flu-like symptoms compared to the placebo during the hospitalization period and 4-week post-discharged (P < 0.05) as compared to the placebo, with a more prevalent effect against lower respiratory tract infections (LRTI). Probio-M8 reduced prescription of antibiotic (P = 0.037), prevented new prescription of antibiotic in non-prescribed patients (P = 0.024) and reduced hospitalization period in antibiotic-prescribed patients (P = 0.004) as compared to the placebo. Oral cytokine levels of TNF-α decreased in the Probio-M8 group (P = 0.001) accompanied by increased in IL-10 (P = 0.018) over 4-week post-discharged, while the placebo group did not exhibit such an effect. Increased IL-10 in the Probio-M8 group was correlated with decreased body ache (r = - 0.296, P = 0.001), headache (r = - 0.295, P = 0.001) and pain during swallow (r = - 0.235, P = 0.010). CONCLUSION: Data from our present study show that B. lactis Probio-M8 could be a potential natural and non-drug strategy for the management of RTI in young children in a safe manner. CLINICAL TRIAL REGISTRATION: Clinical studies (Approval No. USM/JEPeM/19030177) were registered at ClinicalTrials.gov (Identifier No. NCT04122495) on September 30, 2019.

Dosimetric assessment of patient dose calculation on a deep learning-based synthesized computed tomography image for adaptive radiotherapy.

PURPOSE: Dose computation using cone beam computed tomography (CBCT) images is inaccurate for the purpose of adaptive treatment planning. The main goal of this study is to assess the dosimetric accuracy of synthetic computed tomography (CT)-based calculation for adaptive planning in the upper abdominal region. We hypothesized that deep learning-based synthetically generated CT images will produce comparable results to a deformed CT (CTdef) in terms of dose calculation, while displaying a more accurate representation of the daily anatomy and therefore superior dosimetric accuracy. METHODS: We have implemented a cycle-consistent generative adversarial networks (CycleGANs) architecture to synthesize CT images from the daily acquired CBCT image with minimal error. CBCT and CT images from 17 liver stereotactic body radiation therapy (SBRT) patients were used to train, test, and validate the algorithm. RESULTS: The synthetically generated images showed increased signal-to-noise ratio, contrast resolution, and reduced root mean square error, mean absolute error, noise, and artifact severity. Superior edge matching, sharpness, and preservation of anatomical structures from the CBCT images were observed for the synthetic images when compared to the CTdef registration method. Three verification plans (CBCT, CTdef, and synthetic) were created from the original treatment plan and dose volume histogram (DVH) statistics were calculated. The synthetic-based calculation shows comparatively similar results to the CTdef-based calculation with a maximum mean deviation of 1.5%. CONCLUSIONS: Our findings show that CycleGANs can produce reliable synthetic images for the adaptive delivery framework. Dose calculations can be performed on synthetic images with minimal error. Additionally, enhanced image quality should translate into better daily alignment, increasing treatment delivery accuracy.

A review of gynaecological surgical practices for trainees and certified specialists in Australia by volume using MBS and AIHW databases.

BACKGROUND: There is a finite volume of surgery performed annually by trainees and certified specialists alike. The detailed assessment of this surgical substrate is important, since it guides true exposure in gynaecological surgical training and practice after fellowship. AIMS: This study quantifies the volume and profile of major gynaecological surgical procedures performed in Australia within a specified five-year period and discusses the implications for training and practice. MATERIALS AND METHODS: Australian Institute of Health and Welfare data were examined to quantify the total number of major gynaecological procedures performed between 2013 and 2018. Medicare data were analysed to quantify the number of billed procedures. These data were compared with published Australian RANZCOG trainees and operative gynaecologists, to estimate the potential annual average exposure for each procedure. RESULTS: Major open, laparoscopic and vaginal surgeries constitute less than 27% of the 600 000 gynaecological procedures performed annually in Australia. Most major gynaecological surgeries are performed at rates lower than 12 cases per year for both trainees and specialists. Over the study period, laparotomies, vaginal hysterectomies and continence procedures decreased, and operative laparoscopies and laparoscopic hysterectomies increased. CONCLUSIONS: The volume of available major gynaecological procedures in Australia may not allow sufficient exposure for optimal training and practice for all trainees and specialists in operative gynaecology. This shortfall may compromise the ability to obtain and maintain proficiency in some core gynaecological operative procedures.

The Efficacy of Vaginal Laser and Other Energy-based Treatments on Genital Symptoms in Postmenopausal Women: A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review examined energy-based treatments of the vagina for postmenopausal vaginal symptoms. DATA SOURCES: We performed a systematic review from April 2017 (the end date of our previous review) to April 2020, searching Medline, Embase, and Scopus. METHODS OF STUDY SELECTION: The inclusion criteria were all randomized studies, prospective studies with >10 cases, and retrospective studies with >20 cases published in English or French that assessed change in postmenopausal vaginal symptoms and/or sexual function in women after energy-based vaginal treatments. Meta-analyses were performed on randomized data. TABULATION, INTEGRATION, AND RESULTS: Of the 989 results retrieved, 3 randomized studies, 16 prospective studies, and 7 retrospective studies were included in the review, representing data from 2678 participants. Pooled data from 3 randomized controlled trials show no difference between vaginal laser and topical hormonal treatments for change in vaginal symptoms (-0.14, 95% confidence interval -1.07 to 0.80) or sexual function scores (2.22, 95% confidence interval -0.56 to 5.00). Furthermore, no difference among vaginal laser, topical hormone, and lubricant was demonstrated in sexual function (p = .577). As in our previous review, non-randomized data support energy-based treatments in improving vaginal symptoms, sexual function, and clinician-reported outcomes. No severe adverse events were reported in the included studies. Significant heterogeneity of data arising from differing measures and reported outcomes continues to be an issue, with data remaining low quality, with high risk of bias, and no double-blind or placebo-controlled randomized trials yet reported, although 1 has now completed recruitment. CONCLUSION: There are 3 randomized trials comparing energy-based systems with hormonal treatment, with no clinical difference in these 2 approaches. Although prospective data continue to show promising outcomes, without strong evidence from well-powered, double-blind placebo-controlled trials to determine the efficacy of treatment compared with placebo, the use of energy-based treatments should continue to be undertaken in research studies only, with high-quality studies essentially free from bias (International Prospective Register of Systematic Review registration number: 178346).

Effect of Fractional Carbon Dioxide Laser vs Sham Treatment on Symptom Severity in Women With Postmenopausal Vaginal Symptoms: A Randomized Clinical Trial.

Importance: Postmenopausal vaginal symptoms are common and frequently detrimental to a woman's quality of life. Fractional carbon dioxide vaginal laser is increasingly offered as a treatment, but the efficacy remains unproven. Objective: To determine the efficacy of fractional carbon dioxide laser for treatment of vaginal symptoms associated with menopause. Design, Setting, and Participants: A double-blind, randomized, sham-controlled trial with 12-month follow-up was undertaken at a single tertiary referral hospital in Sydney, Australia. Enrollment commenced on September 19, 2016, with final follow-up on June 30, 2020. Participants were postmenopausal women with vaginal symptoms substantive enough to seek medical treatment. Of 232 participants approached, 85 were randomized. Interventions: Three treatments using a fractional microablative carbon dioxide laser system performed 4 to 8 weeks apart, with 43 women randomized to the laser group and 42 to the sham group. Main Outcomes and Measures: The co-primary outcomes were symptom severity assessed using a visual analog scale (VAS; range, 0-100; 0 indicates no symptoms and 100 indicates the most severe symptoms) and the Vulvovaginal Symptom Questionnaire (VSQ; range, 0-20; 0 indicates no symptoms and 20 indicates the most severe symptoms) at 12 months. The minimal clinically important difference was specified as a 50% decrease in both VAS and VSQ severity scores. There were 5 prespecified secondary outcomes, including quality of life (range, 0-100; higher scores indicate better quality of life), the Vaginal Health Index Score (range, 5-25; higher scores indicate better health), and vaginal histology (premenopausal or postmenopausal status). Results: Of 85 randomized participants (mean [SD] age, 57 [8] years), 78 (91.7%) completed the 12-month follow-up. From baseline to 12 months, there was no significant difference between the carbon dioxide laser group and the sham group in change in symptom severity (VAS score for overall vaginal symptoms: -17.2 vs -26.6; difference, 9.4 [95% CI, -28.6 to 47.5]; VAS score for the most severe symptom: -24.5 vs -20.4; difference -4.1 [95% CI, -32.5 to 24.3]; VSQ score: -3.1 vs -1.6; difference, -1.5 [95% CI, -5.9 to 3.0]). There were no significant differences between the laser and sham group in the mean quality of life score (6.3 vs 1.4; difference, 4.8 [95% CI, -3.9 to 13.5]) and Vaginal Health Index Score (0.9 vs 1.3; difference, -0.4 [95% CI, -4.3 to 3.6]) or in histological comparisons between laser and sham treatment groups. There were 16 adverse events in the laser group and 17 in the sham group, including vaginal pain/discomfort (44% vs 68%), spotting, discharge, and lower urinary tract symptoms. No severe adverse events were reported in either group. Conclusions and Relevance: Among women with postmenopausal vaginal symptoms, treatment with fractional carbon dioxide laser vs sham treatment did not significantly improve vaginal symptoms after 12 months. Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616001403426.

Cesarean Scar Pregnancies: A Systematic Review of Treatment Options.

The objective of this systematic review was to assess the efficacy and safety of treatment options of cesarean scar pregnancies (CSPs). We searched MEDLINE, Embase, and the Cochrane Library from inception to June 2016 as well as reference lists. We included English publications reporting treatment outcomes of at least 10 cases of CSPs. Two authors screened for eligibility, extracted data, and assessed the quality of the included studies. Treatment was considered successful if no subsequent intervention was required after the index treatment. Of the 1257 citations identified, 63 studies were eligible. The overall success rate of systemic methotrexate (MTX) and/or local injection of MTX or potassium chloride was 62%. Dilation and curettage (D&C) was associated with a 28% risk of hemorrhage that dropped to 4% when combined with uterine artery embolization (UAE). Hysteroscopic resection of CSP was unsuccessful in 12% of cases, and inadequate human chorionic gonadotropin decay was the primary indication for additional intervention. Laparoscopic, vaginal, and open excision and repair of the defect were associated with a high success rate (≥96%) and a low risk of hemorrhage (≤4%). Expectant management resulted in a 57% live birth rate, but 63% of women required hysterectomy because of placental implantation abnormalities or second trimester uterine rupture. Most studies were of low methodologic quality, and given the heterogeneity between the studies and groups, statistical comparison of treatment options was deemed inappropriate. In conclusion, the decision to allow the progression of CSPs exposes women to a high risk of life-threatening hemorrhage and hysterectomy. Medical treatment options alone are often insufficient. D&C is a reasonable option in well-selected women or when combined with UAE. The potential benefits of excision and repair of scar defect on further pregnancy outcomes need to be further assessed.

Concise reviews: can mesenchymal stromal cells differentiate into corneal cells? A systematic review of published data.

The majority of stem cell therapies for corneal repair are based upon the use of progenitor cells isolated from corneal tissue, but a growing body of literature suggests a role for mesenchymal stromal cells (MSC) isolated from noncorneal tissues. While the mechanism of MSC action seems likely to involve their immuno-modulatory properties, claims have emerged of MSC transdifferentiation into corneal cells. Substantial differences in methodology and experimental outcomes, however, have prompted us to perform a systematic review of the published data. Key questions used in our analysis included: the choice of markers used to assess corneal cell phenotype, the techniques used to detect these markers, adequate reporting of controls, and tracking of MSC when studied in vivo. Our search of the literature revealed 28 papers published since 2006, with half appearing since 2012. MSC cultures established from bone marrow and adipose tissue have been best studied (22 papers). Critically, only 11 studies used appropriate markers of corneal cell phenotype, along with necessary controls. Ten out of these eleven papers, however, contained positive evidence of corneal cell marker expression by MSC. The clearest evidence is observed with respect to expression of markers for corneal stromal cells by MSC. In comparison, the evidence for MSC conversion into either corneal epithelial cells or corneal endothelial cells is often inconsistent or inconclusive. Our analysis clarifies this emerging body of literature and provides guidance for future studies of MSC differentiation within the cornea as well as other tissues.

Evaluation of the AlgerBrush II rotating burr as a tool for inducing ocular surface failure in the New Zealand White rabbit.

The New Zealand White rabbit has been widely used as a model of limbal stem cell deficiency (LSCD). Current techniques for experimental induction of LSCD utilize caustic chemicals, or organic solvents applied in conjunction with a surgical limbectomy. While generally successful in depleting epithelial progenitors, the depth and severity of injury is difficult to control using chemical-based methods. Moreover, the anterior chamber can be easily perforated while surgically excising the corneal limbus. In the interest of creating a safer and more defined LSCD model, we have therefore evaluated a mechanical debridement technique based upon use of the AlgerBrush II rotating burr. An initial comparison of debridement techniques was conducted in situ using 24 eyes in freshly acquired New Zealand White rabbit cadavers. Techniques for comparison (4 eyes each) included: (1) non-wounded control, (2) surgical limbectomy followed by treatment with 100% (v/v) n-heptanol to remove the corneal epithelium (1-2 min), (3) treatment of both limbus and cornea with n-heptanol alone, (4) treatment of both limbus and cornea with 20% (v/v) ethanol (2-3 min), (5) a 2.5-mm rounded burr applied to both the limbus and cornea, and (6) a 1-mm pointed burr applied to the limbus, followed by the 2.5-mm rounded burr applied to the cornea. All corneas were excised and processed for histology immediately following debridement. A panel of four assessors subsequently scored the degree of epithelial debridement within the cornea and limbus using masked slides. The 2.5-mm burr most consistently removed the corneal and limbal epithelia. Islands of limbal epithelial cells were occasionally retained following surgical limbectomy/heptanol treatment, or use of the 1-mm burr. Limbal epithelial cells were consistently retained following treatment with either ethanol or n-heptanol alone, with ethanol being the least effective treatment overall. The 2.5-mm burr method was subsequently evaluated in the right eye of 3 live rabbits by weekly clinical assessments (photography and slit lamp examination) for up to 5 weeks, followed by histological analyses (hematoxylin & eosin stain, periodic acid-Schiff stain and immunohistochemistry for keratin 3 and 13). All 3 eyes that had been completely debrided using the 2.5-mm burr displayed symptoms of ocular surface failure as defined by retention of a prominent epithelial defect (∼40% of corneal surface at 5 weeks), corneal neovascularization (2-3 quadrants), reduced corneal transparency and conjunctivalization of the corneal surface (demonstrated by the presence of goblet cells and/or staining for keratin 13). In conclusion, our findings indicate that the AlgerBrush II rotating burr is an effective method for the establishment of ocular surface failure in New Zealand White rabbits. In particular, we recommend use of the 2.5-mm rotating burr for improved efficiency of epithelial debridement and safety compared to surgical limbectomy.

Botulinum Toxin for the Management of Pelvic Floor Tension Myalgia and Persistent Pelvic Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically review the literature on use of botulinum toxin to treat pelvic floor tension myalgia and persistent pelvic pain. DATA SOURCES: The ClinicalTrials.gov , PubMed, EMBASE, and Scopus databases were searched from inception to November 2022 by two independent assessors (B.L.K. and F.G.L.). Identified studies were screened by title and abstract and included after full-text review. Data extraction was subsequently performed and recorded in Microsoft Excel. METHODS: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines after registration in PROSPERO (CRD42022289132). All randomized studies, prospective studies with more than five participants, and retrospective studies with more than 10 participants published in English or French and assessing the use of botulinum toxin for the treatment of pelvic floor tension myalgia and persistent pelvic pain in women were included. Meta-analyses were performed on randomized data. TABULATION, INTEGRATION, AND RESULTS: Of 4,722 articles identified, 24 satisfied inclusion criteria. A meta-analysis of five randomized controlled trials totaling 329 participants demonstrated no differences in patient- and clinician-reported outcome measures, including pain, dyspareunia, sexual function, and vaginal manometry. Mean duration of follow-up was 6 months. A qualitative analysis of 14 prospective and four retrospective studies including 804 participants is supportive of botulinum toxin; however, the quality of data is low, and there is marked heterogeneity between studies. CONCLUSION: Meta-analyses of randomized data do not support the use of botulinum toxin to treat pelvic floor tension myalgia and persistent pelvic pain. Failure of these data to confirm the findings of nonrandomized prospective studies that suggest a treatment benefit may be attributable to the absence of placebo control and confounding outcomes obtained from an active comparator group. Further randomized controlled trials with true placebo are strongly recommended. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022289132.

Impact of Adapted Radiotherapy Schedules on Bowel Sparing in Node-Positive Cervical Cancer.

PURPOSE: Definitive radiation therapy (RT) for locally advanced node-positive cervical cancer confers significant toxicity to pelvic organs including the small bowel. Gross nodal disease exhibits significant shrinkage during RT, and yet conventional RT does not account for this change. We evaluated the reduction in absorbed bowel dose using various adaptive RT schedules. METHODS AND MATERIALS: We obtained 130 evaluable scans (computed tomography simulation and 25 cone beam computed tomography scans per patient) of 5 patients who had received definitive external beam RT for lymph node positive cervical cancer daily over 5 weeks. Using a single universal volumetric modulated arc therapy plan with predefined optimization priorities, we created adapted RT plans in 4 schedules: Daily, Weekly, Twice, and NoAdapt (mimicking conventional nonadapted RT). The in silico (computer modeled) patients were treated to 45 Gy to primary cervical disease with a simultaneous integrated boost to 55 Gy to involved lymph nodes. We evaluated dose metrics including D2cc, D15cc, and V45 to determine the impact of adapted RT schedules on bowel sparing. Statistical tests included the Student t test, analysis of variance, and the Spearman rank correlation. RESULTS: The quantity of reduced bowel dose was significantly associated with the chosen planning schedule in all evaluated metrics and was proportional to the frequency of adaptive RT with significant moderate-to-strong monotonicity. Both D2cc and D15cc were reduced an average of 2.7 Gy using daily replanning compared with a nonadapted approach. A minimally adapted strategy of only 2 replans also confers a significant dosimetric benefit over a nonadapted approach. Reduced standard deviations of D2cc and V45 bowel doses over the treatment courses were significantly associated with the choice of planning schedule with strong monotonicity. CONCLUSIONS: All adaptive RT schedules evaluated confer significant dosimetric advantages in bowel sparing over a conventional nonadapted technique, with greater sparing seen with more frequent replanning schedules. These findings warrant future trials of adaptive RT for pelvic malignancies.

Noise-Based Image Harmonization Significantly Increases Repeatability and Reproducibility of Radiomics Features in PET Images: A Phantom Study.

For multicenter clinical studies, characterizing the robustness of image-derived radiomics features is essential. Features calculated on PET images have been shown to be very sensitive to image noise. The purpose of this work was to investigate the efficacy of a relatively simple harmonization strategy on feature robustness and agreement. A purpose-built texture pattern phantom was scanned on 10 different PET scanners in 7 institutions with various different image acquisition and reconstruction protocols. An image harmonization technique based on equalizing a contrast-to-noise ratio was employed to generate a "harmonized" alongside a "standard" dataset for a reproducibility study. In addition, a repeatability study was performed with images from a single PET scanner of variable image noise, varying the binning time of the reconstruction. Feature agreement was measured using the intraclass correlation coefficient (ICC). In the repeatability study, 81/93 features had a lower ICC on the images with the highest image noise as compared to the images with the lowest image noise. Using the harmonized dataset significantly improved the feature agreement for five of the six investigated feature classes over the standard dataset. For three feature classes, high feature agreement corresponded with higher sensitivity to the different patterns, suggesting a way to select suitable features for predictive models.

Probiotics Reduce Vaginal Candidiasis in Pregnant Women via Modulating Abundance of Candida and Lactobacillus in Vaginal and Cervicovaginal Regions.

We previously reported on the effects of a lactobacilli probiotic (SynForU-HerCare; two capsules/day of 9.5 log CFU/capsule) in improving symptoms of vaginal irritation, discharge and burning in pregnant women with vaginal candidiasis upon administration for 8 weeks, accompanied by improved emotional and social quality of life parameters. Thus, the present study aimed to analyse vaginal microbiota and inflammatory changes in hope to better understand the improved clinical symptoms as observed previously. Patients in the probiotic group showed a decreased abundance of Candida glabrata after 8 weeks (p = 0.009) in the lower vaginal region, while patients in the placebo group did not show any changes over time. In the higher vaginal and cervicovaginal regions, patients in the placebo group showed a decreased abundance of Candida albicans only within 4 weeks (p < 0.05) but no changes in abundance of C. glabrata over time, while patients in the probiotic group showed a continuous decreased abundance of C. albicans and C. glabrata over 8 weeks (p < 0.05). Patients in the placebo group also had a decreased abundance of Lactobacillus crispatus over 4 weeks (p = 0.023) in the lower vaginal region and a decreased abundance of L. jensenii over 8 weeks in the cervicovaginal region (p = 0.001). Meanwhile, patients in the probiotic group had an increased abundance of L. crispatus in the lower vaginal region after 8 weeks (p = 0.012) and Lactobacillus jensenii over 4 weeks in the cervicovaginal region (p < 0.001). Inflammation may have occurred in both low and high vaginal regions, predominantly observed by the increased concentration of pro-inflammatory cytokine TNF-alpha in patients from the placebo group (p < 0.05), while the administration of probiotics has shortened the period of inflammation as observed from the reduced need for anti-inflammatory cytokine IL-4 and IL-10 over time (p < 0.05). Taken together, our present new data further support previous findings that probiotic SynForU-HerCare had a beneficial effect against vaginal candidiasis in pregnant women via modulation of the vaginal microbiota and microenvironment.

Late-onset persistent Descemet's membrane detachment following uncomplicated clear corneal incision cataract surgery.

We report the case of a 76-year-old man who developed a late-onset Descemet's membrane detachment (DMD) 5 months after uncomplicated cataract surgery. Despite two air tamponade procedures that initially appeared successful, the DMD continued to return. After careful examination it was found that a surgical entry wound may have been scarred open (fish-mouthing), which continually promoted Descemet's membrane to detach. Excision of the abnormal scar led to an almost complete resolution of the DMD. To our knowledge, this is the first report of a pathological (fish-mouthing) entry wound causing a persistent, late DMD. We discuss the reasons why the management of late DMDs requires careful consideration.