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Until recently, research examining the application of Rational Emotive Behavior Therapy (REBT) in sports settings was virtually absent in South Africa. Despite the growing evidence of REBT's potential as a psychological intervention in Western nations, its use within the multicultural and sports-fervent context of South Africa remains unexplored. Moreover, limited research has addressed the impact of REBT on rugby players, with only a few case studies being reported. The current experiment employs a cluster randomized trial (CRT) to compare the effects of a 7-week preferential REBT program with a 7-week Mindfulness-Acceptance-Commitment (MAC) program on irrational beliefs, competitive anxiety and subjective performance, among adolescent South African rugby players. We also include a wait-list control group who received neither REBT nor MAC. Results indicate that athletes receiving REBT reported greater improvements in irrational beliefs, anxiety, and subjective performance, while that athletes receiving MAC also reported some improvements in anxiety. This study highlights the potential of REBT as a valuable psychological intervention in the context of South African adolescent rugby players., Competing Interests: Declaration of competing interest “A cluster randomized trial of a v-emotive behavior therapy program and a mindfulness-acceptance-commitment program, with South African adolescent rugby players," The aforementioned authors affirm that we tried to adhere to the highest ethical standards and scientific integrity when conducting and writing about this research. We affirm that the results presented in this manuscript are based solely on the data collected and analyzed during the course of the study, and they are reported with objectivity and impartiality., (Copyright © 2024. Published by Elsevier Ltd.)

Background/Objectives: Surgical removal of deep endometriosis lesions is an established method of reducing patient symptoms, but it often results in iatrogenic adhesions that lead to further problems. This pilot study presents the safety evaluation of a novel self-cross-linked hyaluronic acid gel used to reduce adhesions after non-bowel deep endometriosis surgery. Methods: A single cohort, single-center, non-randomized pilot study was conducted in patients diagnosed with non-bowel deep endometriosis who underwent a three-stage treatment regimen consisting of first surgery, hormone therapy and second surgery. The present report is limited to an analysis of the inflammatory parameters, pain and complications occurring within a 72 h period following the initial laparoscopy (FLL) utilizing the anti-adhesion gel. Results: 60 patients (28.48 ± 5.9 years old) were included. 24 h after the intervention, a slight elevation in C-reactive protein levels was observed in 38.33% of cases (0.98 ± 1.46 mg/dL), with a statistically significant difference after FLL (0.98 ± 1.46 mg/dL before FLL vs. 1.03 ± 1.29 mg/dL after FLL; p =< 0.001); there were no patients with levels above 10 mg/dL before or after surgery. 24 h after FLL, 29.33% of patients had a leukocyte count greater than 11 Thous/μL, with a maximum observed value of 16.2 Thous/μL. The count was found to be statistically significantly higher after FLL (6.03 ± 1.91 Thous/μL before FLL vs. 9.15 ± 2.61 Thous/μL after FLL; p =< 0.001). At 72 h post-intervention, postoperative pain was reported in up to 63.33% of cases, and one urinary tract infection with fever occurred but was not considered to be related to the product. No serious adverse events were observed. Conclusions: The results of this exploratory study showed a safe range of inflammatory response within a 24 h period following the application of the novel self-cross-linked hyaluronic acid antiadhesion gel (HyaRegen ® ) in patients who underwent laparoscopic surgery for non-bowel deep endometriosis.

Endocrine therapy has become the fundamental treatment option for hormone receptor-positive (HR + ) and receptor tyrosine-protein kinase erbB-2-negative (HER2 - ) metastatic breast cancer (mBC). While treatments incorporating cyclin-dependent kinase (CDK)4 and 6 inhibitors are more prevalent than ever, comparisons among those regimens are scarce. The aim of the present study was to identify the most effective maintenance treatment for patients with HR + and HER2 - mBC. To this end, databases including PubMed, Embase, Cochrane Library, Scopus and Google Scholar were searched from inception to August, 2023. The endpoints comprised overall survival (OS) and progression free survival (PFS). For dichotomous variants, hazard ratios (HRs) and odds ratios (ORs) were generated, while standard mean difference (SMD) was used for consecutive variants by Bayesian network meta-analysis to make pairwise comparisons among regimens, to determine the optimal therapy. These processes were conducted using Rstudio 4.2.2 orchestrated with STATA 17.0 MP. A total of 16 randomized controlled trials including 7,174 patients with 11 interventions were analyzed. Compared with aromatase inhibitor (AI), palbociclib plus AI (PalboAI) exhibited a significantly longer PFS up to the 36th month of follow-up [HR=1.7; 95% credible interval, 1.36-2.16], including on the 3rd [OR=2.22; 95% confidence interval (CI), 1.10-4.47], 6th (OR=2.39; 95% CI, 1.21-4.69), 12th (OR=1.94; 95% CI, 1.34-2.79), 18th (OR=2.38; 95% CI, 1.65-3.44), 24th (OR=2.39; 95% CI, 1.67-3.43), 30th (OR=2.10; 95% CI, 1.62-2.74) and 36th (OR=2.66; 95% CI, 1.37-5.18) month of follow-up. Additionally, abemaciclib plus fulvestrant exhibited significant effects compared with AI alone between 12 and 36 months. Ribociclib plus fulvestrant, ribociclib plus AI and dalpiciclib plus AI exerted significant effects compared with AI alone between 12 and 30 months. Considering the effect on OS and PFS together with adverse reactions, safety, medical compliance and route of administration, PalboAI was found to be the optimal treatment for HR + /HER2 - mBC. However, additional head-to-head clinical trials are warranted to confirm these findings., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Jiang et al.)

Background: Neonates with congenital heart disease (CHD) have smaller brain volume at birth. High rates of placental vascular malperfusion lesions may play a role in disrupted brain development., Methods: This is a single-center retrospective cohort study of infants born between 2010 and 2019 who were diagnosed with a major cardiac defect requiring surgery in the first year of life. Doppler ultrasound RI of the middle cerebral artery (MCA) and anterior cerebral artery were calculated within the first 72 hours of life. Placentas were evaluated using a standardized approach., Results: Over the study period, there were 52 patients with hypoplastic left heart syndrome (HLHS), 22 with single-ventricle right ventricular outflow tract obstruction (SV-RVOTO), 75 with a two-ventricle cardiac defect (2V), and 25 with transposition of the great arteries (TGA). MCA Doppler RI were significantly higher for all subgroups of CHD compared with control subjects (0.68 ± 0.11 in control subjects compared with 0.78 ± 0.13 in HLHS, P = 0.03; 0.77 ± 0.10 in SV-RVOTO, P = 0.002; 0.78 ± 0.13 in 2V, P = 0.03; and 0.80 ± 0.14 in TGA; P = 0.001) with the highest average MCA RI in the TGA group. In subgroup analyses, placental fetal vascular malperfusion in the 2V group was associated with higher MCA RI, but this relationship was not present in other subgroups, nor in regards to maternal vascular malperfusion., Conclusions: Major forms of CHD are associated with significantly higher cerebral artery RI postnatally, but placental vascular malperfusion lesions may not contribute to this hemodynamic adaptation., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The placenta and fetal heart undergo development concurrently during early pregnancy, and, while human studies have reported associations between placental abnormalities and congenital heart disease (CHD), the nature of this relationship remains incompletely understood. Evidence from animal studies suggests a plausible cause and effect connection between placental abnormalities and fetal CHD. Biomechanical models demonstrate the influence of mechanical forces on cardiac development, whereas genetic models highlight the role of confined placental mutations that can cause some forms of CHD. Similar definitive studies in humans are lacking; however, placental pathologies such as maternal and fetal vascular malperfusion and chronic deciduitis are frequently observed in pregnancies complicated by CHD. Moreover, maternal conditions such as diabetes and pre-eclampsia, which affect placental function, are associated with increased risk of CHD in offspring. Bridging the gap between animal models and human studies is crucial to understanding how placental abnormalities may contribute to human fetal CHD. The next steps will require new methodologies and multidisciplinary approaches combining innovative imaging modalities, comprehensive genomic testing, and histopathology. These studies may eventually lead to preventative strategies for some forms of CHD by targeting placental influences on fetal heart development., (© 2024 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Triple negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and mainly affects pre-menopausal and minority women. Because of the lack of ER, PR or HER2 expression in TNBC, there are limited options for tailored therapies. While TNBCs respond initially to standard of care chemotherapy, tumor recurrence commonly occurs within 1 to 3 years post-chemotherapy and is associated with early organ metastasis and a high incidence of mortality. One of the major mechanisms responsible for drug resistance and emergence of organ metastasis is activation of epithelial to mesenchymal transition (EMT) reprogramming. EMT-mediated cancer cell plasticity also promotes the enrichment of cancer cells with a CD44 high /CD24 low and/or ALDH high cancer stem-like phenotype [cancer stem cells (CSCs)], characterized by an increased capacity for tumor self-renewal, intrinsic drug resistance, immune evasion and metastasis. In this study we demonstrate for the first time a positive feedback loop between AURKA and intra-tumoral PD-L1 oncogenic pathways in TNBC. Genetic targeting of intra-tumoral PD-L1 expression impairs the enrichment of ALDH high CSCs and enhances the therapeutic efficacy of AURKA-targeted therapy. Moreover, dual AURKA and PD-L1 pharmacological blockade resulted in the strongest inhibition of tumor growth and organ metastatic burden. Taken together, our findings provide a compelling preclinical rationale for the development of novel combinatorial therapeutic strategies aimed to inhibit cancer cell plasticity, immune evasion capacity and organ metastasis in patients with advanced TNBC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Takchi, Zhang, Jalalirad, Ferre, Shrestha, Haddad, Sarkaria, Tuma, Carter, David, Giridhar, Wang, Lange, Lendahl, Ingle, Goetz and D’Assoro.)

Introduction: Limited data on 24-hour movement behaviors of children aged 5-8 years exist globally. We describe the prevalence and sociodemographic associations of meeting physical activity (PA), sedentary recreational screen time (ST), and sleep guidelines among children from 11 jurisdictions in the US-Affiliated Pacific region., Methods: Cross-sectional representative data from 1192 children aged 5-8 years living in the US-Affiliated Pacific region were drawn from the baseline 2012-2014 Children's Healthy Living Program. Sleep and moderate- to vigorous-intensity PA were calculated from accelerometry. ST and sociodemographic data were collected from caregiver surveys. The percentage of children meeting the Asia-Pacific 24-hour movement guidelines for PA (≥60 min/d of moderate- to vigorous-intensity PA), sleep (≥9 and ≤ 11 h/d) and ST (≤2 h/d) were calculated. Generalized linear mixed models were used to examine associations with adiposity and sociodemographic variables., Results: Twenty-seven percent (95% confidence interval, 24.6-30.0) of children met integrated guidelines; 98% (96.2-98.0) met PA, 78% (75.4-80.0) met sleep, and 35% (32.6-38.0) met ST guidelines. Females (adjusted odds ratio = 1.40 [95% confidence interval, 1.03-1.91]) and those living in lower-middle-income jurisdictions (2.29 [1.49-3.54]) were more likely to meet ST guidelines. Overweight children (0.62 [0.40-0.96]), those aged 8 years (0.39 [0.22-0.69]), and children with caregivers of an education level of high school or beyond (0.44 [0.29-0.68]) were less likely to achieve ST guidelines. Children from midrange annual household incomes were less likely to meet combined guidelines (0.60 [0.39-0.92])., Conclusions: Three-quarters of children are not meeting integrated Asia-Pacific 24-hour movement guidelines. Future strategies for reducing ST and increasing integrated guidelines compliance are needed.

Objectives: Endometriosis is a chronic inflammatory disease known to contribute to infertility. Laparoscopic excision of endometriotic lesions represents a standard treatment modality for symptomatic women. Our study aims to assess the potential benefits of laparoscopic excision of endometriosis in patients experiencing infertility associated with the condition, as well as to define the clinical factors that may impact the cumulative pregnancy rate., Design: In this retrospective analysis, a total of 102 patients with endometriosis-related infertility were enrolled., Materials, Setting, Methods: All participants underwent reproductive surgery and were then categorized into two groups: those who conceived were assigned to group A, while those who did not were assigned to group B. The correlation between clinical factors and pregnancy rate was assessed using the log-rank test, and both univariate and multivariate analyses were conducted utilizing the Cox regression model., Results: The median age of the patients was 33.5 years, with a median follow-up duration of 70 months. Throughout the study period, 71 patients (69.6%) conceived (group A), while the remaining 31 patients (30.4%) did not conceive (group B), irrespective of the use of Assisted-Reproduction Technologies. The Cox regression model revealed that factors such as the duration of infertility, presence of deep infiltrating endometriosis, bowel endometriosis, rASRM stages, pelvic adhesions, and recurrent disease negatively impacted postoperative conception rates. Conversely, complete excision and coagulation of endometriotic lesions, as well as ablation of ovarian endometriomas, emerged as independent positive predictive factors for postoperative clinical pregnancy., Limitations: Limitations of this study is retrospective design of the study, as well as a small number of patients., Conclusions: Complete excision of endometriosis during reproductive surgery may yield a positive effect and optimize the likelihood of pregnancy in patients with endometriosis-related infertility., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: MRI diagnostics are important for adenomyosis, especially in cases with inconclusive ultrasound. This study assessed the potential of MRI-based radiomics as a novel tool for differentiating between uteri with and without adenomyosis. Methods: This retrospective proof-of-principle single-center study included nine patients with and six patients without adenomyosis. All patients had preoperative T2w MR images and histological findings served as the reference standard. The uterus of each patient was segmented in 3D using dedicated software, and 884 radiomics features were extracted. After dimension reduction and feature selection, the diagnostic yield of individual and combined features implemented in the machine learning models were assessed by means of receiver operating characteristics analyses. Results: Eleven relevant radiomics features were identified. The diagnostic performance of individual features in differentiating adenomyosis from the control group was high, with areas under the curve (AUCs) ranging from 0.78 to 0.98. The performance of ML models incorporating several features was excellent, with AUC scores of 1 and an area under the precision-recall curve of 0.4. Conclusions: The set of radiomics features derived from routine T2w MRI enabled accurate differentiation of uteri with adenomyosis. Radiomics could enhance diagnosis and furthermore serve as an imaging biomarker to aid in personalizing therapies and monitoring treatment responses.

Background: Our objectives were to determine 1) the prevalence and description of placental pathologic lesions in pregnancies complicated by SARS-CoV-2 infection compared to healthy controls and 2) whether the prevalence and/ or pattern of placental pathologic lesions differed in the few neonates who tested positive for SARS-CoV-2 in the first 48 hours of life at a busy urban county hospital., Methods: This study included all pregnant mothers who tested positive for SARS-CoV-2 and delivered at our institution from March 2020 to June 2021, while control placentas were collected from term pregnancies without complications., Results: Approximately 90% (n = 380/425) of placentas from pregnancies complicated by SARS-CoV-2 infections had placental pathologic lesions, compared to 32% (n = 16/50) of controls. The predominant lesions were acute histologic chorioamnionitis with or without fetal response (n = 209/380, 55%), maternal vascular malperfusion (n = 180/380, 47%), and other inflammatory lesions (n = 148/380, 39%). Only 14 (2.5%) infants tested positive for SARS-CoV-2 within the first 48 hours of life. There were no significant differences in placental histopathology between infants who tested positive vs. those that were negative for SARS-CoV-2. Placental lesions in mothers who tested positive for SARS-CoV-2 during the first vs. second vs. third pregnancy trimesters, were significantly different in the incidence of inflammatory placental pathologic lesions (n = 9/19, 53% vs. n = 37/98, 49% vs. n = 102/439, 31%, respectively; p < 0.01)., Conclusion: A significant proportion of women with SARS-CoV-2 infection during pregnancy at a single county hospital have inflammatory and vascular placental lesions at birth, raising questions regarding their downstream effects and clinical consequences.

This study aims to summarize evidence from observational studies about the lifetime use of HC and the risk of BC in women of reproductive age. The PubMed, Cochrane, and EMBASE databases were searched for observational studies published from 2015 to February 2022. Meta-analyses were performed using adjusted odds ratios and relative risks with a random-effects model using the I 2 statistic to quantify the heterogeneity among studies. Of the 724 studies identified, 650 were screened for title/abstract selection, 60 were selected for full-text revision, and 22 were included in the meta-analysis. Of these, 19 were case-control studies and 3 were cohort studies. The results of the meta-analysis indicate a significantly higher risk of developing BC in ever users of HC (pooled OR = 1.33; 95% CI = 1.19 to 1.49). This effect is larger in the subgroups of case-control studies (pooled OR = 1.44, 95% CI = 1.21 to 1.70) and in the subgroup of studies that strictly define menopausal status (pooled OR = 1.48; 95% CI, 1.10 to 2.00). Although our meta-analysis of observational studies (cohort and case-control) suggests a significantly increased overall risk of BC in users or ever-users of modern hormonal contraceptives, the high heterogeneity among studies (>70%) related to differences in study design, measurement of variables, confounders, among other factors, as well as publication biases should be considered when interpreting our results.

Diaphragmatic endometriosis is rare and forms 0.67-4.7% of all endometriosis cases. Evidence regarding its optimal management is lacking. In this study, we retrospectively analyzed the patient characteristics and long-term treatment outcomes of diaphragmatic endometriosis patients. Over a 4-year period, 23 patients were diagnosed with diaphragmatic endometriosis. The majority of patients had coexisting deep pelvic endometriosis. Cyclic upper abdominal pain was reported by 60.9% of patients, while cyclic chest and shoulder pain were reported by 43.5% and 34.8% of patients, respectively. Most patients were treated with laparoscopic lesion ablation, while 21.1% were treated with minimally invasive excision. The mean follow-up time was 23.7 months. Long-lasting resolution of the chest, abdominal, and shoulder pain occurred in 50%, 35.7%, and 25% of patients, respectively. Nonetheless, 78.9% of patients reported major improvement in their symptoms postoperatively. Significantly higher rates of postoperative shoulder, abdominal, and chest pain were observed in patients who received postoperative hormonal therapy compared with those who did not. All patients treated expectantly remained stable. Therefore, we recommend treating diaphragmatic endometriosis only in symptomatic patients. The risk of incomplete surgery should be minimized by a multidisciplinary diagnostic and therapeutic approach with a careful assessment of the diaphragm and the thoracic cavity.

Introduction: Women with bladder endometriosis often present with more advanced stages of endometriosis. Robotic surgery has emerged as a promising approach to the management of bladder endometriosis. This systematic review aims to analyze the current literature on robotic surgery for bladder endometriosis and describe our systematic approach to surgical treatment., Methods: This review followed the PRISMA guidelines, which ensured a comprehensive and transparent approach to selecting and evaluating relevant studies. We conducted a thorough literature search to identify studies that investigated the use of robotic surgery for bladder endometriosis. Relevant databases were searched, and inclusion and exclusion criteria were applied to select eligible studies. Data extraction and analysis were performed to assess the outcomes and effectiveness of robotic surgery for the treatment of bladder endometriosis., Results: We did not find any randomized clinical trials with the use of robotics in the treatment of bladder endometriosis. We found only two retrospective studies comparing robotic surgery with laparoscopy, and another retrospective study comparing robotic surgery, laparoscopy, and laparotomy in the treatment of bladder endometriosis. All the other 12 studies were solely case reports. Despite the lack of robust evidence in the literature, the studies demonstrated that robotic surgery is feasible and is associated with reduced postoperative pain, shorter hospital stays, and faster recovery., Conclusions: The utilization of robotic technology is a promising option for the surgical management of bladder endometriosis. We advocate a surgical systematic approach for the robotic treatment of bladder endometriosis. Robotic technology, with its 3D vision, instrumental degrees of freedom, and precision, particularly in suturing, may provide potential benefits over traditional laparoscopy.

The psychological health concerns and risk factors associated with non-communicable disease among adolescents have been prioritized on the agenda of international health institutions globally. The aims of this systematic review are to determine the various types of psycho-educational intervention programmes developed to address the psychological risk factors associated with non-communicable diseases among adolescents, and to assess the effectiveness of the psycho-educational intervention programmes. The systematic review will include case-control and randomized controlled studies. The review will be conducted using the following electronic databases, PubMed, CINAHL, Science Direct, Cochrane Library, SCOPUS, and ERIC, as well as the grey literature for the thesis repository from 2012 to 2022. The key search terms will include intervention programme, adolescents (aged 10-19 years), psychological risk factors and non-communicable diseases. The studies identified by the search strategy will be downloaded into Mendeley and exported to Covidence software for screening, quality assessment and data extraction. The quality assessment tool that will be utilized is the Joanna Briggs Institute critical appraisal checklists to ensure relevance and quality of the articles. This systematic review will use two types of data analysis: narrative synthesis of qualitative studies and meta-analysis of quantitative studies. The findings from this systematic review will provide evidence-based tools for the management of psychological risk factors associated with non-communicable diseases, as well as present key insights for future intervention programmes on the management of psychological risk factors associated with NCDs among adolescents.

Introduction: Pelvic organ prolapse is a common health issue that affects 30.8% of women. Laparoscopic sacrocolpopexy and colpopectopexy are two of the most common procedures to restore the pelvic anatomy. Mesh application on the other hand carries an increased complications risk over the short and long terms. The aim of this study is to provide a basis for meshless sacrocolpopexy and colpopectopexy., Methods: This study is a retrospective cohort pilot study that analyzed the data of patients with a pelvic organ prolapse according to the pelvic organ prolapse quantification system and underwent the modified technique for sacrocolpopexy and colpopectopexy. Descriptive statistics were used to express the different variables., Results: A total of 36 patients met the inclusion criteria and provided consent for the participation in this study. The majority of patients were postmenopausal. 22 out of 36 patients received a previous prolapse surgery. All patients presented with reducible vaginal lump. Dyspareunia and sexual dysfunction were the most commonly reported symptoms. The intraoperative complications rate was 0%. Only one patient had a postoperative persistent urinary retention that was managed medically., Discussion: Sacrocolpopexy and colpopectopexy seems to be a safe alternative to the mesh-based pelvic surgeries with a very low rate of intraoperative complications and favorable follow up outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Devassy, Naem, Krentel and De Wilde.)

Background: Advanced cancer of the cervical stump, occurring years after a laparoscopic supracervical hysterectomy (LASH), is a rare but serious clinical condition. Many patients who undergo a LASH are unaware of this possible complication. Upon diagnosis of advanced cervical stump cancer, a holistic approach including imaging, laparoscopic surgery and multimodal oncological therapy is required., Case Presentation: A 58-year-old patient presented to our department with the suspicion of advanced cervical stump cancer eight years after LASH. She reported pelvic pain, irregular vaginal bleedings and irregular discharge. Gynaecological examination revealed a locally advanced tumor of the uterine cervix with suspicion of infiltration of the left parametria and bladder. After thorough diagnostic imaging and laparoscopic staging, the tumor stage was determined as FIGO IIIB and the patient was treated with combined radiochemotherapy. The patient presented with tumor recurrence 5 months after the completion of therapy and she is currently being treated with multichemotherapy and immunotherapy regimens as palliative treatment., Conclusion: Patients should be made aware about the risk of cervical stump carcinoma after LASH and the necessity for regular screening. Cervical cancer after LASH is often diagnosed at advanced stages and the treatment requires an interdisciplinary approach., (© 2023. The Author(s).)

Contained electromechanical morcellation has emerged as a safety approach for laparoscopic myomatous tissue retrieval. This retrospective single-center analysis evaluated the bag deployment practicability and safety of electromechanical in-bag morcellation when used for big surgical benign specimens. The main age of patients was 39.3 years (range 21 to 71); 804 myomectomies, 242 supracervical hysterectomies, 73 total hysterectomies, and 1 retroperitoneal tumor extirpation were performed. A total of 78.7% of specimens weighed more than 250 g (n = 881) and 9% more than 1000 g. The largest specimens, weighing 2933 g, 3183 g, and 4780 g, required two bags for complete morcellation. Neither difficulties nor complications related to bag manipulation were recorded. Small bag puncture was detected in two cases, but peritoneal washing cytology was free of debris. One retroperitoneal angioleiomyomatosis and three malignancies were detected in histology (leiomyosarcoma = 2; sarcoma = 1); therefore, patients underwent radical surgery. All patients were disease-free at 3 years follow-up, but one patient presented multiple abdominal metastases of the leiomyosarcoma in the third year; she refused subsequent surgery and was lost from follow-up. This large series demonstrates that laparoscopic bag morcellation is a safe and comfortable method to remove large and giant uterine tumors. Bag manipulation takes only a few minutes, and perforations rarely occur and are easy to detect intraoperatively. This technique did not result in the spread of debris during myoma surgery, potentially avoiding the additional risk of parasitic fibroma or peritoneal sarcoma.

Background: Many aspects of care for fetuses and neonates with congenital heart disease (CHD) fall outside standard practice guidelines, leading to the potential for significant variation in clinical care for this vulnerable population., Methods: We conducted a cross-sectional survey of site sponsors of the Children's Hospitals Neonatal Consortium, a multicenter collaborative of 41 Level IV neonatal intensive care units to assess key areas of clinical practice variability for patients with fetal and neonatal CHD., Results: We received responses from 31 centers. Fetal consult services are shared by neonatology and pediatric cardiology at 70% of centers. Three centers (10%) routinely perform fetal magnetic resonance imaging (MRI) for women with pregnancies complicated by fetal CHD. Genetic testing for CHD patients is routine at 76% of centers. Preoperative brain MRI is standard practice at 5 centers (17%), while cerebral NIRS monitoring is regularly used at 14 centers (48%). Use of electroencephalogram (EEG) after major cardiac surgery is routine in 5 centers (17%). Neurodevelopmental follow-up programs are offered at 30 centers (97%)., Conclusions: Many aspects of fetal and neonatal CHD care are highly variable with evolving shared multidisciplinary models., Impact: Many aspects of fetal and neonatal CHD care are highly variable. Genetic testing, placental examination, preoperative neuroimaging, and postoperative EEG monitoring carry a high yield of finding abnormalities in patients with CHD and these tests may contribute to more precise prognostication and improve care. Evidence-based standards for prenatal and postnatal CHD care may decrease inter-center variability., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: Our aim was to examine the frequency and type of placental abnormalities in neonates with LSV., Study Design: We prospectively reviewed cranial ultrasounds (cUS) from neonates born at ≤32 weeks of gestation at Parkland Hospital between 2012 and 2014. Our cohort included neonates with LSV and gestational age and sex matched controls with normal cUS. We retrieved placental pathology reports retrospectively and compared placental abnormalities in both groups., Results: We reviewed 1351 cUS from a total of 407 neonates. Placental pathology evaluations were complete for 64/65 (98%) neonates with LSV and 68/70 (97%) matched controls. There were no significant differences for any type of placental abnormities between LSV and control groups. However, infants with highest stage LSV were more likely to have large for gestational age (LGA) placentas (p = 0.01)., Conclusion: The association between LSV and LGA placenta may indicate a shared vascular response to an adverse prenatal environment., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Study Objective: To test the hypothesis that intraperitoneal instillation of a single bolus dose of l-alanyl-l-glutamine (AG) will reduce the incidence, extent and/or severity of adhesions following myomectomy and establish preliminary safety and tolerability of AG in humans., Design: Phase 1,2 Randomized, double-blind, placebo-controlled study (DBRCT)., Setting: Tertiary care gynecology surgical centre., Patients: Thirty-eight women who underwent myomectomies by laparoscopy (N = 38; AG-19 vs Placebo-19) or laparotomy (N = 10; AG-5 vs Placebo-5) with a scheduled second-look laparoscopy (SLL) 6-8 weeks later. Thirty-two patients in the laparoscopy arm completed SLL., Interventions: Bolus dose of AG or normal saline solution control (0.9% NaCl) administered intraperitoneally immediately prior to suture closure of the laparoscopic ports. The average dose was 170 mL of AG or control based on a dosing scheme of 1 g/kg bodyweight., Measurements: Digital recordings obtained for all procedures. The primary endpoint was reduction in the incidence, severity and extent of post-operative adhesions analyzed by intention-to-treat (ITT) approach. Three independent, blinded reviewers evaluated all operative video recordings to assess presence of adhesions. Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity. Secondary endpoints assessed safety and tolerability of AG., Main Results: Administration of AG reduced the incidence, severity and/or extent of post-operative adhesions (p = 0.046). The presence of adhesions in the AG group was lower than in the Control group (p = 0.041). Adhesion improvement was achieved in 15 of 15 (100%) in the AG group versus 5 of 17 (29.6%) in the placebo group. No serious adverse events were reported. No differences in safety parameters were observed., Conclusions: Intraperitoneal l-alanyl-l-glutamine reduced adhesion formation in all patients following laparoscopic myomectomy. Complete absence of adhesions was achieved at all abdominal sites in 93% of patients. Results confirm AG's known effects on cellular mechanisms of adhesiogenesis and lay the foundation for new adhesion prophylaxis research and treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Surgical experience and hospital procedure volumes have been associated with the risk of severe complications in expert centers for endometriosis in France. However, little is known about other certified units in Central European countries., Material and Methods: This retrospective observational study included 937 women who underwent surgery for colorectal endometriosis between January 2018 and January 2020 in 19 participating expert centers for endometriosis. All women underwent complete excision of colorectal endometriosis by rectal shaving, discoid or segmental resection. Postoperative severe complications were defined as grades III-IV of the Clavien-Dindo classification system including anastomotic leakage, fistula, pelvic abscess and hematoma. Surgical outcomes of centers performing less than 40 (group 1), 40-59 (group 2) and ≥60 procedures (group 3) over a period of 2 years were compared., Results: The overall complication rate of grade III and IV complications was 5.1% (48/937), with rates of anastomotic leakage, fistula formation, abscess and hemorrhage in segmental resection, discoid resection and rectal shaving, respectively, as follows: anastomotic leakage 3.6% (14/387), 1.4% (3/222), 0.6% (2/328); fistula formation 1.6% (6/387), 0.5% (1/222), 0.9%; (3/328); abscess 0.5% (2/387), 0% (0/222) and 0.6% (2/328); hemorrhage 2.1% (8/387), 0.9% (2/222) and 1.5% (5/328). Higher overall complication rates were observed for segmental resection (30/387, 7.8%) than for discoid (6/222, 2.7%, P = 0.015) or shaving procedures (12/328, 3.7%, P = 0.089). No significant correlation was observed between the number of procedures performed and overall complication rates (r Spearman  = -0.115; P = 0.639) with a high variability of complications in low-volume centers (group 1). However, an intergroup comparison revealed a significantly lower overall severe complication rate in group 3 than in group 2 (2.9% vs 6.9%; P = 0.017) without significant differences between other groups., Conclusions: A high variability in complication rates does exist in centers with a low volume of activity. Major complications may decrease with an increase in the volume of activity but this effect cannot be generally applied to all institutions and settings., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Fetuses with congenital heart disease are at increased risk of perinatal morbidity and mortality, which is highly influenced by their prenatal health. Placental function is vital for the health of the fetus, but increased rates of pathologic lesions of the placenta have been observed in pregnancies complicated by fetal congenital heart disease., Objective: This study aimed to determine the prevalence of both gross and histologic placental pathologies in a cohort of pregnancies complicated by fetal congenital heart disease vs healthy controls using the Amsterdam Placental Workshop Group Consensus Statement sampling and definitions of placental lesions., Study Design: This single-center retrospective cohort study included placental examinations from pregnancies diagnosed prenatally with fetal congenital heart disease between 2010 and 2019; moreover, control placentas were collected from pregnancies without maternal or fetal complications. Placentas were sampled and evaluated according to the Amsterdam Placental Workshop Group Consensus Statement and gross and histopathologic diagnoses determined., Results: Approximately 80% of fetuses diagnosed with congenital heart disease (n=305) had a placental examination for comparison with controls (n=40). Of note, 239 placentas (78%) in the group with fetal congenital heart disease had at least 1 gross or histopathologic lesion compared with 11 placentas (28%) in the control group (P<.01). One-third of placentas complicated by fetal congenital heart disease met the criteria for small for gestational age, and 48% of placentas had one or more chronic lesions, including maternal vascular malperfusion (23% vs 0%; P<.01), villitis of unknown etiology (22% vs 0%; P<.01), fetal vascular malperfusion (20% vs 0%; P<.01), and other chronic lesions (16% vs 0%; P<.01). Acute inflammation was equally present in both the group with fetal congenital heart disease and the control group (28% vs 28%; P=1.00). Although gestational age and birthweight z score were similar between the 2 groups, birth head circumference was 1.5 cm less in pregnancies complicated by fetal congenital heart disease with a significantly lower z score compared with the control group (-0.52±1.22 vs 0.06±0.69; P<.01)., Conclusion: Vascular malperfusion lesions and chronic forms of inflammation occur at markedly higher rates in placentas complicated by fetal congenital heart disease, which may contribute to the decreased head circumference at birth. Further work in neuroplacentology is needed to explore connections among cardiac defects, placental vascular malperfusion lesions, and fetal brain development., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To determine the birth prevalence of perinatal stroke in term born infants at our high-volume delivery center and assess the frequency of both gross and histologic placental pathologies associated with perinatal stroke using the Amsterdam Placental Workshop Group Consensus Statement guidelines and definitions., Study Design: A single-center retrospective cohort study spanning 2010-2020., Results: There were 129,759 live births at Parkland Hospital during the study period and a total of 18 term born infants leading to a birth prevalence of 1 in 6,829 infants. Perinatal risk factors were found in all but one patient, and 74% presented with seizures. Pathologic placental examination was available in 56% of the cohort and only one patient had normal placental examination. Acute histologic chorioamnionitis was described in five placentas (50%) and an additional two had isolated umbilical and/or chorionic plate vasculitis with or without funisitis compared to a rate of 28% with acute inflammation in a Control group. Chronic inflammation in the form of villitis of unknown etiology was described in three of the acutely inflamed placentas and was high-grade in each of those while none of the placentas from our Control group showed evidence of any chronic lesion., Conclusion: Both acute and chronic placental inflammation are common in perinatal stroke; placental examination should be considered an essential component to the diagnostic workup., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Leon, Kalvacherla, Andrews, Thomas, Mir and Chalak.)

Objective: The ideal management of early-stage cervical cancer has become the subject of a global controversy following the publication of a prospective study in 2018 that reported a worse oncologic outcome when comparing the minimally invasive approach to the laparotomy approach. The discussion involves both prospective and retrospective data and general and theoretical considerations. We wanted to look at the data available today and review the different opinions, offering an impartial assessment of the ongoing controversy., Methods: The available literature was reviewed, focusing on articles arguing for and against minimally invasive surgery in cervical cancer. We tried to avoid any fundamental bias, as is often evident in the available reviews on the subject. Literature both before and after the 2018 publication was taken into consideration., Results: As is usual in discussions of concepts, the literature that is now available provides arguments for both sides of this challenging issue, depending on one's standpoint. Science-related writing is not immune to trends. There is a curious shift in opinion seen before and after 2018. One must question whether there was a prejudice in favor of minimally invasive surgery prior to the publication of the NEJM articles and a bias against it afterward., Conclusion: Whether further minimally invasive surgery for cervical cancer is invariable is tied to the more pressing question of how this surgery will have to be centralized in the future. Unless these questions are linked, no satisfactory solution can be found.

A technical video was produced to demonstrate in step-by-step fashion a multiple contained myomectomy of a 20 × 30 cm giant myoma and seven additional fibroids found in the same patient, which required two different types of specimen retrieval bags for the electronic power morcellation. This complete surgical procedure included leiomyomata enucleation, contained in-bag electronic power morcellation, uterine reconstruction and the application of an adhesion prophylactic medical product.

Background: The infiltration of CD8 T cells is usually linked to a favorable prognosis and may predict the therapeutic response of breast cancer patients to immunotherapy. The purpose of this research is to investigate the competing endogenous RNA (ceRNA) network correlated with the infiltration of CD8 T cells., Methods: Based on expression profiles, CD8 T cell abundances for each breast cancer (BC) patient were inferred using the bioinformatic method by immune markers and expression profiles. We were able to extract the differentially expressed RNAs (DEmRNAs, DEmiRNAs, and DElncRNAs) between low and high CD8 T-cell samples. The ceRNA network was constructed using Cytoscape. Machine learning models were built by lncRNAs to predict CD8 T-cell abundances. The lncRNAs were used to develop a prognostic model that could predict the survival rates of BC patients. The expression of selected lncRNA (XIST) was validated by quantitative real-time PCR (qRT-PCR)., Results: A total of 1,599 DElncRNAs, 89 DEmiRNAs, and 1,794 DEmRNAs between high and low CD8 T-cell groups were obtained. Two ceRNA networks that have positive or negative correlations with CD8 T cells were built. Among the two ceRNA networks, nine lncRNAs (MIR29B2CHG, NEAT1, MALAT1, LINC00943, LINC01146, AC092718.4, AC005332.4, NORAD, and XIST) were selected for model construction. Among six prevalent machine learning models, artificial neural networks performed best, with an area under the curve (AUC) of 0.855. Patients from the high-risk category with BC had a lower survival rate compared to those from the low-risk group. The qRT-PCR results revealed significantly reduced XIST expression in normal breast samples, which was consistent with our integrated analysis., Conclusion: These results potentially provide insights into the ceRNA networks linked with T-cell infiltration and provide accurate models for T-cell prediction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Feng, Kahlert, Chen, Torres-dela Roche, Soliman, Miao, De Wilde and Shi.)

Objective: In the field of endometriosis, several classification, staging and reporting systems have been developed, but do clinicians routinely use these classification systems, which system do they use and what are the clinicians' motivations?, Data Sources: A cross-sectional study was performed to gather data on the current use of endometriosis classification systems, problems encountered and interest in a new simple surgical descriptive system for endometriosis. Of particular focus were three systems most commonly used: the Revised American Society for Reproductive Medicine (rASRM) classification, the Endometriosis Fertility Index (EFI), and the ENZIAN classification. Data were analysed by SPSS. A survey was designed using the online SurveyMonkey tool consisting of 11 questions concerning three domains-participants background, existing classification systems and intentions with regards to a new classification system for endometriosis. Replies were collected between 15 May and 1 July 2020., Methods of Study Selection: na TABULATION, INTEGRATION AND RESULTS: The final dataset included the replies of 1178 clinicians, including surgeons, gynecologists, reproductive endocrinologists, fertility specialists and sonographers, all managing women with endometriosis in their clinical practice. Overall, 75.5% of the professionals indicate that they currently use a classification system for endometriosis. The rASRM classification system was the best known and used system, the EFI system and ENZIAN system were known by a majority of the professionals but used by only a minority. The lack of clinical relevance was most often selected as a problem with using any system. The findings of the survey suggest that clinicians worldwide are open to using a new classification system for endometriosis that can achieve standardized reporting, and is clinically relevant and simple. The findings therefore support future initiatives for the development of a new descriptive system for endometriosis and provide information on user expectations and conditions for universal uptake of such a system., Conclusion: Even with a high uptake of the existing endometriosis classification systems (rASRM, ENZIAN and EFI), most clinicians managing endometriosis would like a new simple surgical descriptive system for endometriosis., (Copyright © 2022. Published by Elsevier Inc.)

Background: Adenomyosis can cause symptoms like dysmenorrhea, dyspareunia, pelvic pain and bleeding disorders and is related to subfertility and obstetrical complications. The disease is probably underestimated and underdiagnosed because of difficulties in reliable clinical examination and imaging results. The age-related prevalence of adenomyosis still remains unclear. In this retrospective analysis we describe the rate of adenomyosis in two independent cohorts of patients undergoing hysterectomy for benign diseases (2011-2013 and 2015-2018) and its correlation to presurgical symptoms respectively indications for hysterectomy., Materials and Methods: All surgeries have been performed in the same department of minimally invasive gynecological surgery by a total of two experienced surgeons following a surgical internal standard for the indication bleeding disorder, dysmenorrhea. We analyzed the overall rate of patients with adenomyosis in both cohorts and related the histological presence of adenomyosis to presurgical symptoms. We also analyzed a subgroup of postmenopausal patients with uterine prolapse., Results: In 307 patients we detected 42.0% of cases with histologically proven adenomyosis. In the group of patients with bleeding disorders and dysmenorrhea as indication for surgery we found the highest rate of adenomyosis (59.3%, cohort 1). 81,1% patients with adenomyosis (cohort 1) reported symptoms. In the subgroup of 42 postmenopausal patients, we found 23.8% of cases with adenomyosis., Conclusion: Our data shows that a positive anamnesis regarding the symptoms bleeding disorders and dysmenorrhea is suspicious for adenomyosis. In hysterectomy specimen adenomyosis can be found in more than 40%. The role of adenomyosis-related symptoms requires further investigation, especially in adolescent and postmenopausal patients., Competing Interests: The authors have no conflict of interest., (© 2022 The Authors.)

(1) Background: Uterine niche is a frequent condition in patients with a history of cesarean section. Although the relation to uterotomy seems to be clear, the exact pathogenesis is not fully understood. Uterine niche can easily be diagnosed by transvaginal ultrasound. It can be related to symptoms like dysmenorrhea, bleeding disorders, dysuria and dyspareunia. Uterine niche can be the cause of scar pregnancy, a rare form of ectopic pregnancy which can be related to severe complications; (2) Methods: We present a series of nine cases with different uterine niche related findings and discuss the diagnostic and therapeutic options reviewing the current literature and introduce a novel intrauterine ICG use for laparoscopic niche detection in one case; (3) Results: Most of uterine niche related symptoms and complications can be treated by a minimally invasive approach. Laparoscopic fluorescence guided niche detection is feasible; (4) Conclusions: Hysteroscopic and laparoscopic techniques allow the treatment of uterine niche related symptoms and complications. Intrauterine ICG application during fluorescence guided laparoscopy may allow easy niche detection.

Adhesions are a common consequence of abdomino-pelvic surgery. Efficacy of available adhesion prevention agents is discussed controversially. Here, we used the adhesion barrier 4DryField PH: a powder, which is transformed into a barrier gel with saline solution. The study includes 40 consecutive patients with surgeries for adhesiolysis, endometriosis and other gynaecological pathologies and subsequent second look interventions. The intervention group ( n  = 17) received 4DryField PH gel while control patients ( n  = 23) did not receive any adhesion prevention. Severity and extent of adhesion formation were scored during both interventions using an established score. Direct comparison between first and second interventions showed that extent and severity of adhesions could be reduced significantly using 4DryField PH gel. In contrast, in the control group, extent was not reduced and severity was even significantly higher. Direct comparison of second look laparoscopies revealed that adhesion extent and severity were significantly lower in the 4DryField PH than in the control group.Impact Statement What is already known on this subject? Adhesion formation after gynaecologic surgeries is known to be frequent and highly problematic as it directly induces complications and additionally makes subsequent surgeries more difficult. The effectiveness of established adhesion barriers is not sufficient to tackle these problems adequately. What the results of this study add? This is the first controlled study using the relatively new adhesion barrier 4DryField PH. It yields a significant reduction of extent as well as severity of adhesions, while adhesiolysis surgery alone does not solve the problem. What the implications are of these findings for clinical practice and/or further research? Usage of 4DryField PH gel seems to be a good approach to solve the adhesion problem of gynaecologic surgery in general and the reformation problem of adhesiolysis surgery specifically. The results should be confirmed in a larger prospective randomised controlled trial.

Objective: Therapeutic hypothermia (TH) is currently the only effective therapy available to improve outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) and has maximal effect when initiated within 6 hours of birth. Neonates affected by HIE are commonly born outside of cooling centers and transport is a barrier to timely initiation. In this study, we sought to determine if the initiation of servo-controlled TH in transport allowed neonates to reach target temperature earlier, without a significant delay in the transfer process, for both local and long-distance transport., Study Design: In this single-center cohort study of neonates referred to a level IV neonatal intensive care unit for TH, we determined the chronologic age at which target temperature was reached for those cooled in transport. Short-term outcome measures were assessed, including survival, incidence of electrographic seizures, discharge feeding method, and length of hospitalization., Results: In a study population of 85 neonates, those receiving TH during transport ( n  = 23), achieved target temperature (33-34°C) 77 minutes sooner (230 ± 71 vs. 307 ± 79 minutes of life (MOL); p  < 0.001). Locally transported neonates (<15 miles) achieved target temperature 69 minutes earlier (215 ± 48 vs. 284 ± 74 MOL; p  < 0.01). TH during long-distance transports allowed neonates to reach target temperature 81 minutes sooner (213 ± 85 vs. 294 ± 79 MOL; p  < 0.01). Infants who were cooled in transport discharged 4 days earlier (13.7 ± 8 vs. 17.8 ± 13 days; p  = 0.18) and showed a significantly higher rate of oral feeding at discharge (95 vs. 71%; p  = 0.03)., Conclusion: For those starting TH in transport, time to target temperature was decreased. In our cohort, cooling in transport was associated with improved short-term outcomes, although additional studies are needed to correlate these findings with long-term outcomes., Key Points: · Therapeutic hypothermia started during transport allows shorter time to target temperature.. · Transfer was minimally delayed by starting cooling in transport.. · Cooling in transport was associated with increased rate of oral feeding at hospital discharge.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: MicroRNAs (miRNAs) play key roles in a variety of pathological processes by interacting with their specific target mRNAs for translation repression and may function as oncogenes (oncomiRs) or tumor suppressors (TSmiRs). Therefore, a web server that could predict the regulation relations between miRNAs and small molecules is expected to achieve implications for identifying potential therapeutic targets for anti-tumor drug development. Methods: Upon obtaining positive/known small molecule-miRNA regulation pairs from SM2miR, we generated a multitude of high-quality negative/unknown pairs by leveraging similarities between the small molecule structures. Using the pool of the positive and negative pairs, we created the Dataset1 and Dataset2 datasets specific to up-regulation and down-regulation pairs, respectively. Manifold machine learning algorithms were then employed to construct models of predicting up-regulation and down-regulation pairs on the training portion of pairs in Dataset1 and Dataset2, respectively. Prediction abilities of the resulting models were further examined by discovering potential small molecules to regulate oncogenic miRNAs identified from miRNA sequencing data of endometrial carcinoma samples. Results: The random forest algorithm outperformed four machine-learning algorithms by achieving the highest AUC values of 0.911 for the up-regulation model and 0.896 for the down-regulation model on the testing datasets. Moreover, the down-regulation and up-regulation models yielded the accuracy values of 0.91 and 0.90 on independent validation pairs, respectively. In a case study, our model showed highly-reliable results by confirming all top 10 predicted regulation pairs as experimentally validated pairs. Finally, our predicted binding affinities of oncogenic miRNAs and small molecules bore a close resemblance to the lowest binding energy profiles using molecular docking. Predictions of the final model are freely accessible through the PSRR web server at https://rnadrug.shinyapps.io/PSRR/. Conclusion: Our study provides a novel web server that could effectively predict the regulation of miRNAs expression by small molecules., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Li, Sun, Qi, De Wilde, Torres-de la Roche, Li, Ahmad, Shi, Li and Chen.)

Postoperative adhesions represent a frequent complication of abdominal surgery. Adhesions can result from infection, ischemia, and foreign body reaction, but commonly develop after any surgical procedure. The morbidity caused by adhesions affects quality of life and, therefore, it is paramount to continue to raise awareness and scientific recognition of the burden of adhesions in healthcare and clinical research. This 2021 Global Expert Consensus Group worked together to produce consented statements to guide future clinical research trials and advise regulatory authorities. It is critical to harmonize the expectations of research, to both develop and bring to market improved anti-adhesion therapies, with the ultimate, shared goal of improved patient outcomes.

Background: Here, we describe an innovative oncoplastic technique for small to medium volume breasts with a tumor in the lower quadrant and this technique could provide sufficient tissue to avoid visible defects after tumor removal and help reshape the natural shape of the breast., Methods: A detailed procedure for the folding flap technique is described step by step. Then, the results of a retrospective analysis of patients treated using this technique, including complications and disease recurrence rate, between January 2017 and November 2021 are reported. Aesthetic outcomes were evaluated on a 5-point scale proposed by the Paris Breast Center., Results: A total of 52 patients underwent surgery with the folding flap technique, The average operation time was 98.4 min (range, 75-120 min), and the mean bleeding volume was 56.5 mL (range, 20-100 mL). A margin-positive result was confirmed in 1 patient who underwent re-excision. Short-term postoperative complications were observed in 7 patients, including 4 with fat liquefaction, 2 with seroma, and 1 with skin redness and swelling. No flap necrosis was observed. The median follow-up time was 28.6 months (range, 9-58 months), and 2 patients experienced local recurrence. The mean aesthetic score was 4.7 points, with 36 patients scoring 5 points and 26 patients scoring 4 points, respectively., Conclusions: The folding flap technique, as an innovative and favorable oncoplastic technique for treating small- to medium-volume breasts with a tumor in the lower quadrant, could retain sufficient tissue to fill the residual cavity after the operation while improving the aesthetic outcome of the breast., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Wang, Torres-de la Roche, Shi, Gong, Dong, Chen, Zeng, Jiang, Chen, Wu, Zhuo and De Wilde.)

Here, we describe a step-by-step novel level I oncoplastic technique and present the aesthetic results of 58 breast cancer patients who underwent the spoon-shape technique for primary tumor resection. The Paris Breast Center's 5-point scale was used to evaluate the aesthetic outcomes. The median age of the participants was 52 years old. The average size of the resected tumor was 22.1 mm; two intraoperative re-excisions were required due to positive margins. Postoperative localized seroma was observed in four patients, and one patient presented signs of wound infection. Skin flap necrosis and fat liquefaction were not observed. The average aesthetic score was 4.86. None of the patients presented cancer recurrence in the following two years. The spoon-shape technique showed good aesthetic results because it provided the surgeons an adequate amount of surrounding tissue from which to reshape the breast after tumor removal. We encourage surgeons to apply this approach in early-stage breast cancer, regardless of the quadrant where the tumor is located.

Children with congenital heart disease (CHD) are living longer due to effective medical and surgical management. However, the majority have neurodevelopmental delays or disorders. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. In this review, we summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. We review differences in the structure and function of the placenta in pregnancies complicated by fetal CHD and introduce the concept of a placental inefficiency phenotype that occurs in severe forms of fetal CHD, characterized by a myriad of pathologies. We propose that in CHD placental dysfunction contributes to decreased fetal cerebral oxygen delivery resulting in poor brain growth, brain abnormalities, and impaired neurodevelopment. We conclude the review with key areas for future research in neuroplacentology in the fetal CHD population, including (1) differences in structure and function of the CHD placenta, (2) modifiable and nonmodifiable factors that impact the hemodynamic balance between placental and cerebral circulations, (3) interventions to improve placental function and protect brain development in utero, and (4) the role of genetic and epigenetic influences on the placenta-heart-brain connection. IMPACT: Neuroplacentology seeks to understand placental connections to fetal brain development. In fetuses with CHD, brain growth abnormalities begin in utero. Placental microstructure as well as perfusion and function are abnormal in fetal CHD., (© 2021. The Author(s).)

This study was conducted to provide information regarding the chemistry-including structure, synthesis, formulation, and mechanical properties-of two types of chemically modified anti-adhesion gels made of hyaluronic acid. Gel A (Hyalobarrier ® ) and gels B and C (HyaRegen ® and MetaRegen ® ) that are used in postsurgical adhesion prevention. To date, little information is available on their physicochemical attributes. This information is necessary in order to understand the differences in their in vivo behavior., Methods: Comparative analyses were conducted under laboratory-controlled conditions, including measuring the shear viscosity, storage modulus G', peel strength, and extrusion forces., Results: All polymers exhibited viscoelastic behavior. Polymer A showed a shear viscosity approximately three times larger than both polymers B and C (114 Pa.s -1 vs. 36-38 Pa.s -1 ) over the shear-rate range measured, indicating a possible better ability to resist flows and potentially remain in place at the site of application in vivo. The results of storage modulus (G') measurements showed 100 Pa for polymer A and 16 Pa and 20 Pa for polymers B and C, respectively. This translated into a weaker elastic behavior for gels B and C, and a lower ability to resist sudden deformation. The peel test results showed a rupture strength of 72 mN (0.016 lbf) for polymer A, 39.6 mN (0.0089 lbf) for polymer B, and 38.3 mN (0.0086 lbf) for polymers C, indicating possible higher adhesive properties for polymer A. Tests measuring the extrudability of the hyaluronic acid gels in their commercial syringes showed an average extrusion force of 20 N (4.5 lbf) for polymer A, 28 N (6.33 lbf) for polymer B, and 17 N (3.79 lbf) for polymer C., Conclusions: Modified anti-adhesion gels made of hyaluronic acid differed in mechanical properties and concentration. Further clinical studies are needed to confirm whether these differences make one polymer easier to apply during surgery and more likely to stay in place longer after in vivo application, and to determine which is potentially superior in terms of preventing adhesions.

Minimally invasive interventions for myomata treatment have gained acceptance due to the possibility of preserving fertility with reduced trauma induced by laparotomy as way of entrance. There are insufficient data regarding outcomes of high intensity focused ultrasound (HIFU) in non-Asiatic women. Therefore, we revised the available evidence to present an expert opinion that could support physicians, patients and policy-makers for considering this approach in other populations. We revisited systematic reviews, randomized controlled trials and cohort studies from January 2018 to August 2021 using PubMed and Google scholar, regarding short and long term outcomes after ablation with focused ultrasound waves. In total, 33 studies, including 114,810 adult patients showed that outcomes of this approach depend on several parameters directly related with resistance to thermal ablation, especially fibroid size and vascularization. Two studies report satisfactory outcomes in Afro-American women. In accordance to the technique used, fibroid volume reduction showed to be higher in fibroids <300 cm 3 after ultrasound guided HIFU than after MRI guided. Compared to myomectomy and uterine artery embolization, HIFU seems to have shorter hospital stay, higher pregnancy rates and similar adverse events rates, with skin burn being the most reported. Symptoms and quality of life improvement is similar to myomectomy but lower than embolization, however reintervention rate is higher after HIFU. Lacks evidence about long-term sarcoma risk after ablation. Available evidence shows that HIFU can be considered as a uterine sparing treatment for women of different ethnicities suffering of uterine myomatosis, especially for those wishing to preserve their fertility.

Cerebrovascular pressure autoregulation promotes stable cerebral blood flow (CBF) across a range of arterial blood pressures. Cerebral autoregulation (CA) is a developmental process that reaches maturity around term gestation and can be monitored prenatally with both Doppler ultrasound and magnetic resonance imaging (MRI) techniques. Postnatally, there are key advantages and limitations to assessing CA with Doppler ultrasound, MRI, and near-infrared spectroscopy. Here we review these CBF monitoring techniques as well as their application to both fetal and neonatal populations at risk of perturbations in CBF. Specifically, we discuss CBF monitoring in fetuses with intrauterine growth restriction, anemia, congenital heart disease, neonates born preterm and those with hypoxic-ischemic encephalopathy. We conclude the review with insights into the future directions in this field with an emphasis on collaborative science and precision medicine approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Leon, Ortigoza, Ali, Angelis, Wolovits and Chalak.)

Objective: In the field of endometriosis, several classification, staging and reporting systems have been developed. Which endometriosis classification, staging and reporting systems have been published and validated for use in clinical practice?, Data Sources: A systematic PUBMED literature search was performed. Data were extracted and summarized., Methods of Study Selection: na TABULATION, INTEGRATION AND RESULTS: Twenty-two endometriosis classification, staging and reporting systems have been published between 1973 and 2021, each developed for specific, and different, purposes. There still is no international agreement on how to describe the disease. Studies evaluating the different systems are summarized showing a discrepancy between the intended and the evaluated purpose, and a general lack of validation data confirming a correlation with pain symptoms or quality of life for any of the current systems. A few studies confirm the value of the ENZIAN system for surgical description of deep endometriosis. With regards to infertility, the endometriosis fertility index has been confirmed valid for its intended purpose., Conclusion: Of the 22 endometriosis classification, staging and reporting systems identified in this historical overview, only a few have been evaluated for the purpose for which they were developed. The literature search was limited to PUBMED. Unpublished classification, staging or reporting systems, or those published in books were not considered. It can be concluded that there is no international agreement on how to describe endometriosis or how to classify it, and that most classification/staging systems show no or very little correlation with patient outcomes. This overview of existing systems is a first step in working towards a universally accepted endometriosis classification., Competing Interests: Conflict of Interest Dr. Horne reports grant funding from the MRC, NIHR, CSO, Wellbeing of Women, Roche Diagnostics, Astra Zeneca, Ferring, Charles Wolfson Charitable Trust, Standard Life, Consultancy fees from Roche Diagnostics, AbbVie, Nordic Pharma and Ferring, outside the submitted work; In addition, Dr. Horne has a patent Serum biomarker for endometriosis pending. Dr. Johnson reports personal fees from Abbott, Guerbet, Myovant Sciences, Vifor Pharma, Roche Diagnostics, personal fees from Abbott, Guerbet, personal fees from Guerbet, Myovant Sciences, Vifor Pharma, Roche Diagnostics, outside the submitted work; he is also President of the World Endometriosis Society and chair of the trust board. Dr. Missmer reports grants and personal fees from AbbVie, and personal fees from Roche outside the submitted work. Dr. Tomassetti reports grants, non-financial support and other from Merck SA, non-financial support and other from Gedeon Richter, non-financial support from Ferring Pharmaceuticals, outside the submitted work and without private revenue. Dr. Zondervan reports grants from Bayer Healthcare, MDNA Life Sciences, Roche Diagnostics Inc, Volition Rx, outside the submitted work; she is also a Board member (Secretary) of the World Endometriosis Society and World Endometriosis Research Foundation, Research Advisory Board member of Wellbeing of Women, UK (research charity), and Chair, Research Directions Working Group, World Endometriosis Society. The other authors had nothing to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Different classification systems have been developed for endometriosis, using different definitions for the disease, the different subtypes, symptoms and treatments. In addition, an International Glossary on Infertility and Fertility Care has been published in 2017 by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) in collaboration with other organisations. An international working group convened over the development of a classification or descriptive system for endometriosis. As a basis for such system, a terminology for endometriosis was considered a condition sine qua non. The aim of the current study was to develop a set of terms and definitions be prepared on endometriosis that would be the basis for standardization in disease description, classification and research., Data Sources: The working group listed a number of terms relevant to be included in the terminology, documented currently used and published definitions, and discussed and adapted them until consensus was reached within the working group. Following stakeholder review, further terms were added, and definitions further clarified. Although definitions were collected through published literature, the final set of terms and definitions is to be considered consensus-based. After finalization of the first draft, the members of the international societies and other stakeholders were consulted for feedback and comments, which lead to further adaptations., Methods of Study Selection: na TABULATION, INTEGRATION, AND RESULTS: A list of 49 terms and definitions in the field of endometriosis is presented, including a definition for endometriosis and its subtypes, different locations, interventions, symptoms and outcomes. Endometriosis is defined as a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process., Conclusion: The current paper outlines a list of 49 terms and definitions in the field of endometriosis. The application of the defined terms aims to facilitate harmonization in endometriosis research and clinical practice. Future research may require further refinement of the presented definitions., Competing Interests: Conflict of interest A.W.H. reports grant funding from the MRC, NIHR, CSO, Wellbeing of Women, Roche Diagnostics, Astra Zeneca, Ferring, Charles Wolfson Charitable Trust, Standard Life, Consultancy fees from Roche Diagnostics, AbbVie, Nordic Pharma and Ferring, outside the submitted work. In addition, A.W.H. has a patent Serum biomarker for endometriosis pending. N.P.J. reports personal fees from Abbott, Guerbet, Myovant Sciences, Vifor Pharma, Roche Diagnostics outside the submitted work; he is also President of the World Endometriosis Society and chair of the trust board. S.M. reports grants and personal fees from AbbVie, and personal fees from Roche outside the submitted work. C.T. reports grants, nonfinancial support and other from Merck SA, non-financial support and other from Gedeon Richter, non-financial support from Ferring Pharmaceuticals, outside the submitted work and without private revenue. K.T.Z. reports grants from Bayer Healthcare, MDNA Life Sciences, Roche Diagnostics Inc, Volition Rx, outside the submitted work; she is also a Board member (Secretary) of the World Endometriosis Society and World Endometriosis Research Foundation, Research Advisory Board member of Wellbeing of Women, UK (research charity), and Chair, Research Directions Working Group, World Endometriosis Society. J.P reports personal fees from Hologic, Inc., outside the submitted work; he is also a member of the executive boards of ASRM and SRS. The other authors had nothing to disclose., (Copyright © 2021 AAGL. All rights reserved.)

Introduction: The development of peritoneal adhesions and the effects of different antiadhesion agents on such mechanisms are not fully understood. Temporary rises of the C-reactive protein (CRP) level have been reported after antiadhesion agent application. We present the changes of inflammation markers observed after use of a starch-based polysaccharide certified for adhesion prevention and hemostasis 4DF (4DryField ® PH)., Method: Retrospective comparative analysis of inflammation markers in 40 patients undergoing laparoscopic adhesiolysis with or without adhesion prophylaxis was conducted. Statistical comparisons were performed by means of paired or unpaired t tests (for normally distributed continuous data), Wilcoxon matched pairs signed-rank tests or Mann-Whitney tests (for not-normally distributed continuous data), Mantel-Cox tests (for continuous data describing time intervals), and Fisher's exact tests (for discrete data)., Results: The maximum post-operative CRP level was significantly elevated in the 4DF group (87 vs. 29%; p < 0.001), whereas leukocyte concentration and body temperature did not differ between groups. No signs of infection were detected in any of the patients and CRP levels spontaneously dropped to normal values within few days. No side effects or complications were observed in both groups. In second-look surgeries performed for other diagnoses 1-56 weeks after the first interventions, no remnants of 4DF or any peritoneal inflammatory reactions were observed., Conclusion: The starch-based polysaccharide 4DF can be considered safe and does not induce inflammatory reactions of clinical significance. Further studies regarding 4DF degradation are recommended and, apart from macrophage migration, could also examine corresponding markers such as IL-6 and PCT., (© 2021. The Author(s).)

Background: Plasma levels of angiopoietin-2 (ANGPT2) and angiopoietin-like 4 protein (ANGPTL4) reflect different pathophysiological aspects of cardiovascular disease. We evaluated their association with outcome in a hospitalized Norwegian patient cohort (n = 871) with suspected acute coronary syndrome (ACS) and validated our results in a similar Argentinean cohort (n = 982)., Methods: A cox regression model, adjusting for traditional cardiovascular risk factors, was fitted for ANGPT2 and ANGPTL4, respectively, with all-cause mortality and cardiac death within 24 months and all-cause mortality within 60 months as the dependent variables., Results: At 24 months follow-up, 138 (15.8%) of the Norwegian and 119 (12.1%) of the Argentinian cohort had died, of which 86 and 66 deaths, respectively, were classified as cardiac. At 60 months, a total of 259 (29.7%) and 173 (17.6%) patients, respectively, had died. ANGPT2 was independently associated with all-cause mortality in both cohorts at 24 months [hazard ratio (HR) 1.27 (95% confidence interval (CI), 1.08-1.50) for Norway, and HR 1.57 (95% CI, 1.27-1.95) for Argentina], with similar results at 60 months [HR 1.19 (95% CI, 1.05-1.35) (Norway), and HR 1.56 (95% CI, 1.30-1.88) (Argentina)], and was also significantly associated with cardiac death [HR 1.51 (95% CI, 1.14-2.00)], in the Argentinean population. ANGPTL4 was significantly associated with all-cause mortality in the Argentinean cohort at 24 months [HR 1.39 (95% CI, 1.15-1.68)] and at 60 months [HR 1.43 (95% CI, 1.23-1.67)], enforcing trends in the Norwegian population., Conclusions: ANGPT2 and ANGPTL4 were significantly associated with outcome in similar ACS patient cohorts recruited on two continents., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT00521976. ClinicalTrials.gov Identifier: NCT01377402., (© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Immune checkpoint blockade (ICB) has been approved for the treatment of triple-negative breast cancer (TNBC), since it significantly improved the progression-free survival (PFS). However, only about 10% of TNBC patients could achieve the complete response (CR) to ICB because of the low response rate and potential adverse reactions to ICB., Methods: Open datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were downloaded to perform an unsupervised clustering analysis to identify the immune subtype according to the expression profiles. The prognosis, enriched pathways, and the ICB indicators were compared between immune subtypes. Afterward, samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset were used to validate the correlation of immune subtype with prognosis. Data from patients who received ICB were selected to validate the correlation of the immune subtype with ICB response. Machine learning models were used to build a visual web server to predict the immune subtype of TNBC patients requiring ICB., Results: A total of eight open datasets including 931 TNBC samples were used for the unsupervised clustering. Two novel immune subtypes (referred to as S1 and S2) were identified among TNBC patients. Compared with S2, S1 was associated with higher immune scores, higher levels of immune cells, and a better prognosis for immunotherapy. In the validation dataset, subtype 1 samples had a better prognosis than sub type 2 samples, no matter in overall survival (OS) (p = 0.00036) or relapse-free survival (RFS) (p = 0.0022). Bioinformatics analysis identified 11 hub genes (LCK, IL2RG, CD3G, STAT1, CD247, IL2RB, CD3D, IRF1, OAS2, IRF4, and IFNG) related to the immune subtype. A robust machine learning model based on random forest algorithm was established by 11 hub genes, and it performed reasonably well with area Under the Curve of the receiver operating characteristic (AUC) values = 0.76. An open and free web server based on the random forest model, named as triple-negative breast cancer immune subtype (TNBCIS), was developed and is available from https://immunotypes.shinyapps.io/TNBCIS/., Conclusion: TNBC open datasets allowed us to stratify samples into distinct immunotherapy response subgroups according to gene expression profiles. Based on two novel subtypes, candidates for ICB with a higher response rate and better prognosis could be selected by using the free visual online web server that we designed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Wang, De Wilde, Feng, Su, Torres-de la Roche and Shi.)

Background: Vietnam is undergoing a fast-aging process that poses potential critical issues for older people and central among those is demand for healthcare utilization. However, healthcare utilization, here measured as count data, creates challenges for modeling because such data typically has distributions that are skewed with a large mass at zero. This study compares empirical econometric strategies for the modeling of healthcare utilization (measured as the number of outpatient visits in the last 12 months) and identifies the determinants of healthcare utilization among Vietnamese older people based on the best-fitting model identified., Methods: Using the Vietnam Household Living Standard Survey in 2006 (N = 2426), nine econometric regression models for count data were examined to identify the best-fitting one. We used model selection criteria, statistical tests and goodness-of-fit for in-sample model selection. In addition, we conducted 10-fold cross-validation checks to examine reliability of the in-sample model selection. Finally, we utilized marginal effects to identify the factors associated with the number of outpatient visits among Vietnamese older people based on the best-fitting model identified., Results: We found strong evidence in favor of hurdle negative binomial model 2 (HNB2) for both in-sample selection and 10-fold cross-validation checks. The marginal effect results of the HNB2 showed that ethnicity, region, household size, health insurance, smoking status, non-communicable diseases, and disability were significantly associated with the number of outpatient visits. The predicted probabilities for each count event revealed the distinct trends of healthcare utilization among specific groups: at low count events, women and people in the younger age group used more healthcare utilization than did men and their counterparts in older age groups, but a reverse trend was found at higher count events., Conclusions: The high degree of skewness and dispersion that typically characterizes healthcare utilization data affects the appropriateness of the econometric models that should be used in modeling such data. In the case of Vietnamese older people, our study findings suggest that hurdle negative binomial models should be used in the modeling of healthcare utilization given that the data-generating process reflects two different decision-making processes., (© 2021. The Author(s).)