Objective To compare cervical cytological profiles between two distinct real-world screening pathways represented by public tertiary and private outpatient services in Romania and to examine age-adjusted associations between screening pathway and prespecified cytological outcomes. Study design This retrospective comparative cohort study included 1,441 consecutive women undergoing routine cervical cancer screening in two Romanian healthcare settings. The public cohort comprised 726 conventional Papanicolaou smears obtained at a tertiary referral hospital, whereas the private cohort included 715 ThinPrep® liquid-based cytology examinations performed within a private outpatient network.Additionally, hrHPV testing was available for a clinically selected subgroup of 68 women from the private outpatient pathway and was performed according to routine clinical indications.Cytological findings were classified according to the 2014 Bethesda System. Between-group differences were evaluated using Pearson’s chi-square test with post-hoc analysis of adjusted standardized residuals.Age-adjusted logistic regression was used to examine associations between screening pathway and prespecified cytological outcomes. Results A total of 1,441 women were included (public, n = 726; private, n = 715). Age distributions were comparable between healthcare settings (39.4 ± 13.4 vs. 38.3 ± 12.9 years; p = 0.120).The overall prevalence of abnormal cytology was comparable between the public and private pathways (7.4 % vs. 9.5 %; age-adjusted OR [aOR] for public vs. private, 0.77; 95 % CI 0.53–1.12; p = 0.168), whereas the distribution of Bethesda diagnostic categories differed significantly (χ2 = 21.70; p < 0.001). LSIL was more frequent in the private outpatient pathway, while ASC-H and the prespecified ASC-H/HSIL/AGC cytological composite were more frequent in the public tertiary pathway in age-adjusted analyses. Estimates for outcomes with small event counts, particularly ASC-H, were imprecise and should be interpreted cautiously.In the clinically selected private subgroup undergoing hrHPV testing, hrHPV positivity was associated with abnormal cytology (OR 6.91, 95 % CI 2.16–22.10; p = 0.001). Conclusions Two distinct real-world cervical screening pathways showed comparable overall rates of abnormal cytology but different distributions of selected Bethesda categories. These differences remained apparent in age-adjusted analyses; however, healthcare setting was structurally aligned with cytological preparation method, and several potentially relevant patient-level determinants were unavailable. The findings should therefore be interpreted as associations between distinct screening pathways rather than as independent or causal effects of public versus private healthcare. The higher frequency of ASC-H in the public tertiary pathway, without a corresponding statistically significant difference in HSIL, should not be interpreted as evidence of a greater burden of confirmed high-grade disease.
Research question What is the prognostic value of first complete IVF cycle outcomes on live birth rates in the second cycle, and does this differ by age group in contemporary IVF practice? Design Retrospective cohort study using Swiss national IVF registry data. Included were 1,860 women who completed two complete consecutive IVF cycles between 2018 and 2023. An historical cohort comprising 2,162 women whose first and second complete IVF cycles were both initiated between 2014 and 2017 was analysed using identical methods to compare the contemporary findings with an earlier treatment period. Outcomes of the first complete cycle (no pregnancy, biochemical pregnancy, clinical miscarriage, live birth) were used to predict live birth in the second complete cycle, analyzed with multivariable logistic regression adjusted for age and ovarian response and grouped by age (<38 vs. ≥ 38 years). Results Second-cycle live birth showed a graded association: 31.8 % (no pregnancy), 36.6 % (biochemical), 43.1 % (miscarriage), 42.7 % (live birth; p < 0.001). Clinical pregnancy/live birth in first cycle increased odds vs. no pregnancy (aOR 1.41, 95 %CI 1.07–1.86, p = 0.010), with a stronger effect in women < 38 years; age was the predominant prognostic factor in those ≥ 38 years. Comparison with the historical 2014–2017 cohort demonstrated stronger prognostic effects. Conclusions First complete IVF cycle outcomes stratify prognosis for subsequent success, particularly in women < 38 years, while age overtakes as predominant predictor in older women. Biochemical pregnancy was not confirmed as an independent predictor in the main multivariable model. These findings support cautious, individualised counselling after the first complete IVF cycle in contemporary practice, while underscoring that prognostic estimates are conditional on completing a second cycle and should be validated in larger, independent cohorts.
Study question What are the diagnostic roles of hysteroscopy and endometrial biopsy in the evaluation of chronic endometritis (CE), and how is CE associated with reproductive outcomes in women undergoing in vitro fertilization (IVF) or embryo transfer? Summary answer Chronic endometritis was associated with lower clinical pregnancy rates and higher miscarriage risk following IVF or embryo transfer, whereas treated/resolved CE was associated with more favorable reproductive outcomes than persistent disease, based predominantly on observational evidence.Hysteroscopy demonstrated variable diagnostic performance and should be considered an adjunct to histopathological assessment rather than a standalone diagnostic test. What is known already Chronic endometritis is increasingly recognized as a potential contributor to infertility, recurrent implantation failure, and recurrent pregnancy loss. Histopathological identification of endometrial stromal plasma cells, typically supported by CD138 immunohistochemistry, represents the principal tissue-based approach to CE diagnosis. Hysteroscopy may identify characteristic endometrial abnormalities, including micropolyps, stromal oedema, and focal hyperaemia, but its diagnostic performance as a standalone test remains uncertain. Interpretation of the available evidence is complicated by substantial heterogeneity in diagnostic criteria, plasma-cell thresholds, patient populations, and assisted reproductive technology protocols. Study design, size, duration This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 Statement and prospectively registered in PROSPERO (CRD420251130136). MEDLINE, Embase, Scopus, Web of Science Core Collection, and CENTRAL were searched from database inception to February 2026. Thirty-nine studies met the predefined eligibility criteria. Participants/materials, setting, methods Eligible studies included infertile women undergoing IVF or embryo transfer in whom CE was evaluated by hysteroscopy with or without endometrial biopsy. Histopathological assessment, with or without CD138 immunohistochemistry according to study-specific protocols, served as the reference standard, where applicable. Primary outcomes included live birth or ongoing pregnancy, clinical pregnancy, and miscarriage, whereas secondary outcomes included implantation rate and the diagnostic performance of hysteroscopy. Random-effects meta-analyses were performed to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Prespecified subgroup analyses evaluated treatment status and inflammatory burden according to CD138 plasma-cell thresholds. The certainty of evidence for all critical reproductive outcomes was assessed using the GRADE approach. Main results and the role of chance Compared with women without CE, live birth or ongoing pregnancy tended to be lower (44.0% vs 50.6%; OR 0.77, 95% CI 0.53–1.11; I2 = 57%), although the pooled estimate did not reach statistical significance. Clinical pregnancy rates were lower (54.3% vs 60.1%; OR 0.55, 95% CI 0.42–0.74; I2 = 77%), whereas miscarriage rates were higher (16.4% vs 11.9%; OR 1.43, 95% CI 1.13–1.82; I2 = 48%). Compared with persistent chronic endometritis, treated or resolved disease was associated with higher live birth or ongoing pregnancy rates (OR 2.72, 95% CI 1.94–3.82; I2 = 62%), higher clinical pregnancy rates (OR 2.45, 95% CI 1.72–3.50; I2 = 75%), and lower miscarriage rates (OR 0.40, 95% CI 0.20–0.81; I2 = 35%). No statistically significant differences were observed according to higher versus lower CD138 plasma-cell thresholds. Across diagnostic studies, hysteroscopic sensitivity ranged from 22% to 86%, whereas specificity was generally moderate to high when compared with histopathological assessment. Limitations, reasons for caution The available evidence was derived predominantly from observational studies and was affected by substantial clinical and methodological heterogeneity, including differences in patient populations, CE definitions, CD138 thresholds, hysteroscopic interpretation, antibiotic regimens, embryo-transfer protocols, and outcome definitions. These limitations preclude causal inference, and the certainty of evidence was low or very low across the principal reproductive outcomes, reflecting the predominantly observational evidence base together with outcome-specific concerns regarding risk of bias, inconsistency, imprecision, and potential small-study effects. Wider implications of the findings Current evidence supports an association between CE and less favorable reproductive outcomes following IVF or embryo transfer but does not establish that treatment itself improves live birth. Hysteroscopy should be considered an adjunctive diagnostic tool interpreted together with histopathological assessment rather than a definitive diagnostic test. Routine CE screening before a first IVF cycle cannot currently be recommended on the basis of the available evidence. Instead, a targeted rather than universal approach to CE evaluation may be considered in selected women, particularly those with recurrent implantation failure, recurrent pregnancy loss, or otherwise unexplained infertility.Future adequately powered prospective studies and randomized controlled trials using standardized diagnostic criteria, uniform CD138-positive plasma-cell thresholds, and live birth as the primary patient-important outcome are required to clarify whether targeted diagnosis and treatment of CE improve reproductive outcomes. Registration number PROSPERO CRD420251130136.
BACKGROUND:Endometriosis is a chronic gynecological disease associated with pelvic pain and dyspareunia that negatively affects sexual function. Physical rehabilitation programs have emerged as a non-pharmacological therapeutic alternative; however, evidence regarding their effectiveness remains limited. OBJECTIVES:To analyze the effectiveness of physical rehabilitation programs on sexual function in women with endometriosis, assessed using the Female Sexual Function Index (FSFI). METHODS:A systematic review with meta-analysis was conducted following PRISMA guidelines. Searches were performed in PubMed, Web of Science, Scopus, and the Cochrane Library, including randomized controlled trials involving women with endometriosis undergoing physical rehabilitation interventions. Methodological quality was assessed using the CASPe checklist and the Jadad Scale. Standardized mean differences (SMD) with 95% confidence intervals (95% CI) were analyzed using a random-effects model. RESULTS:Results showed a trend toward improved sexual function in the intervention group; however, no statistically significant differences were observed (SMD = 0.12; 95% CI: -0.39 to 0.63). Given the small number of studies and clinical variability between interventions, these findings should be interpreted cautiously. CONCLUSIONS:Physical rehabilitation programs may have a potential beneficial effect on sexual function in women with endometriosis; however, the available evidence remains limited and inconclusive, and the pooled estimate should be interpreted as exploratory. Further adequately powered randomized controlled trials with standardized rehabilitation protocols are needed.
OBJECTIVE:Polycystic kidney disease (PKD) is a genetic condition characterized by the growth of multiple renal cysts that affect kidney function. Although the disease is present from conception, individuals with the more common form of the disease, autosomal dominant PKD, often remain asymptomatic until after reproductive age. There is a paucity of large studies on PKD and obstetric outcomes; hence, the purpose of the present study is to evaluate maternal and neonatal/fetal outcomes in patients with PKD. METHODS:A retrospective cohort study was executed using the 2016-2021 Healthcare Cost Utilization Project-National Inpatient Sample, an American database. Among a cohort of pregnant patients, ICD-10 codes Q61.x were used to identify cases of PKD. The adjusted effects of PKD on maternal and neonatal outcomes were evaluated using multivariable logistic regression models, controlling for maternal age. RESULTS:Compared with non-PKD patients, those with PKD were more often Caucasian, obese, and had pre-existing hypertension and chronic kidney disease. PKD patients were more likely to deliver via cesarean section and experience obstetric complications, including preeclampsia, gestational diabetes, anemia, genitourinary tract infections, abruptio placenta, postpartum hemorrhage, sepsis, renal calculi, acute renal failure, and death. Neonates born to PKD patients were at greater risk of preterm birth, intrauterine growth restriction, and congenital anomalies. CONCLUSION:PKD patients and their fetuses are at greater risk for obstetric complications and should be considered high-risk patients. As such, their pregnancies should be followed closely by a multi-disciplinary team of obstetricians, nephrologists, and neonatologists.
Introduction/background Women with pre-existing cardiovascular disease (CVD) face elevated maternal and fetal risks and implementing existing cardio-obstetric guidelines remains challenging. A previous integrated preconception care pathway for this population has been developed. As a next step, the aim of the current work was to develop a practical, expert-based integrated care pathway (ICP) for women with intermediate to high CVD risk during antepartum and postpartum periods. Methods The integrated obstetric cardiology pathway was developed via a review of international cardiac and obstetric guidelines, and was complemented based on clinical experience by an interdisciplinary expert panel, including health care professionals from Antwerp University Hospital and Erasmus MC, incorporating clinical experience and consensus meetings to establish a standardised, evidence-based care model. Results Coordinated care, and inclusive, patient-centred communication are important context factors. Different healthcare provider specialties address preconception assessment separately. Key ICP steps include the first visit, second and early third trimester visits to a specialised clinic, birth planning, and postpartum follow-up. At the first visit, it is important to confirm the pregnancy. Then, patients should see a dedicated cardiologist, undergo medication review with substitution for pregnancy-safe options if needed, and receive psychosocial assessment. The interdisciplinary team should (re)assess risk, plan follow-up, and arrange genetic counselling when indicated. In the second trimester, routine obstetric care should incorporate symptom monitoring and education on warning signs. In the late second to early third trimester, a birth plan should be defined, covering delivery methods, (duration of) haemodynamic monitoring, pain management, and medication or fluid restrictions. Postpartum care includes planning close monitoring for CVD complications, cardiovascular assessment at predefined timepoints, and ongoing (psychosocial) symptom surveillance. Conclusion This expert-developed ICP offers a structured, practical approach to managing intermediate- to high-risk CVD in pregnancy and postpartum, supporting consistent, evidence-based cardio-obstetric care to improve maternal outcomes.
OBJECTIVE:To compare maternal and neonatal outcomes among large-for-gestational-age neonates with and without prenatal ultrasound suspicion of large-for-gestational-age. STUDY DESIGN:We conducted a population-based retrospective cohort study of term large-for-gestational-age births in Ontario, Canada (2012-2021) using linked health administrative data. Outcomes included labour interventions, maternal complications, and neonatal outcomes. Propensity scores with overlap weights were applied in modified Poisson regression models. RESULTS:Among 82,359 large-for-gestational-age births, 3,969 (4.8%) had prenatal ultrasound suspicion of large-for-gestational-age. After adjustment, suspected large-for-gestational-age had higher rates of induction (aIRR [adjusted incidence rate ratio] 1.48, 95% CI 1.44-1.52), planned cesarean (2.76, 2.54-3.00), unplanned cesarean (1.40, 1.33-1.48), postpartum hemorrhage (1.16, 1.06-1.27), shoulder dystocia (1.10, 1.02-1.19), and neonatal intensive care unit admission (1.33, 1.23-1.43). Operative vaginal delivery and obstetric trauma rates were lower among deliveries with suspected large-for-gestational-age (0.69, 0.61-0.79 and 0.83, 0.72-0.96 respectively). In sensitivity analyses 1) removing gestational hypertension variables from the propensity score and 2) including those without a documented complication of suspected-large-for-gestation-age but a late third trimester ultrasound to the exposed group, results were similar to the main analysis. CONCLUSION:Prenatal ultrasound suspicion of large-for-gestational-age is associated with altered management but does not reduce cesarean delivery or shoulder dystocia but is effective in reducing operative vaginal delivery and obstetric trauma in a cohort of confirmed large-for-gestational-age births. Sensitivity analyses accounting for potential mediating factors and misclassification bias further supported the above findings.
STUDY OBJECTIVE:To assess the temporal associations between the implementation of robotic-assisted surgery (RAS) and changes in the hysterectomy surgical approach for benign disease, with a focus on open surgery (OS). METHODS:Multicentre retrospective hospital-level ecological study using data from the French national medico-administrative database Programme de Médicalisation des Systèmes d'Information (PMSI). All patients who underwent hysterectomy for benign gynaecologic indications between January 1, 2012, and December 31, 2023. Fourteen university hospitals within the Assistance Publique-Hôpitaux de Paris (AP-HP) network were divided into two groups: a robotic hospital group which included seven centres where a RAS platform was implanted in 2019, and a non-robotic hospital group which included seven centres where the RAS platform was implemented. Hysterectomy was performed via OS, conventional laparoscopy vaginal, or RAS approaches. RESULTS:A total of 17,170 benign hysterectomies were included (11,668 (68.0%) in the robotic hospital group and 5,502 (32.0%) in the non-robotic hospital group). Between 2012 and 2018, OS rates decreased similarly in both groups (-5.6%/year vs. -5.3%/year; p = 0.97). Between 2019 and 2023, trends diverged significantly (p < 0.01): OS continued to decline in the robotic hospital group (-5.9%/year) but remained stable in the non-robotic hospital group (+0.6%/year). In the robotic hospital group, RAS increased to 32% by 2023, partially substituting conventional laparoscopy. CONCLUSION:In this academic hospital network, RAS implementation was temporally associated with lower OS routes rates for benign hysterectomy, although robotic surgery widely replaced laparoscopy. In centres where robotic surgery was not performed, the laparotomy rate did not decrease.
OBJECTIVES:This study aimed to evaluate the efficacy of integrating Qigong with pelvic floor muscle training (PFMT) for managing mild to moderate stress urinary incontinence (SUI) in postpartum women. The hypothesis was that the combined intervention would lead to better outcomes compared to PFMT alone by addressing both physical and psychological aspects of recovery. METHODS:A 12-week intervention was conducted, where postpartum women with mild to moderate SUI were divided into three groups: standard PFMT (PFMT group), Qigong combined with PFMT (QGPFMT group), or Qigong-only (QG group). The study assessed pelvic floor muscle function, severity of symptoms and psychological well-being using various validated measures, including the Incontinence Impact Questionnaire-7 (IIQ-7), the Urinary Distress Inventory-6, and Perceived Stress Scale (PSS) scores. RESULTS:The QGPFMT group significantly improved pelvic floor muscle activity, urinary incontinence frequency, and the UDI-6 scores. However, the groups had no significant differences regarding psychological well-being measures, such as the IIQ-7 and PSS scores. CONCLUSIONS:The integration of Qigong with PFMT provides a promising holistic approach for managing postpartum SUI. While physical improvements were significant, psychological improvements may require a longer duration or additional psychological interventions to be fully realized. Future studies should consider the combination of psychological therapies to improve the overall efficacy of treatment for postpartum women with SUI.
BACKGROUND:Rectal endometriosis is among the most symptomatic forms of the disease. When hormonal therapy fails, surgery is often required. High-intensity focused ultrasound (HIFU) is widely used in gynecology for the treatment of myomas and adenomyosis. Transrectal robotic HIFU has previously been used for the treatment of rectal endometriosis, and the clinical outcomes of this approach have been published. To our knowledge, this is the first publication of a dedicated video demonstrating this approach and detailing the technology, treatment planning and procedural steps. TECHNIQUE:The HIFU probe is inserted into the rectum under sonographic guidance. The rectal nodule is visualized and delineated by the physician using the imaging transducer. The software then divides the nodule into several slices. For each slice, the physician outlines the area to be treated. Based on the defined surface, the software calculates the number and location of HIFU shots needed to cover the entire lesion. Once all treatment zones are defined, the probe automatically positions itself at the lower edge of the lesion. The therapeutic transducer then delivers the HIFU energy, and the robotic system sequentially treats all predefined slices under real-time monitoring. Average procedure duration is 35 min, with treatment performed as an outpatient procedure. EXPERIENCE:Transrectal HIFU has undergone progressive clinical evaluation through prospective feasibility and multicentre safety studies, followed by comparative evaluation with conventional surgery. Published studies have reported a favorable safety profile, improvement in gynecological and digestive symptoms, and shorter hospitalization compared with surgery. CONCLUSION:Transrectal robotic HIFU for rectal endometriosis appears to be a promising, minimally invasive alternative to surgery, with short treatment duration, low morbidity and significant symptom improvement. TWEETABLE STATEMENT:Robotic transrectal high-intensity focused ultrasound offers a minimally invasive alternative to surgery for rectal endometriosis, with short procedure time, low morbidity and significant symptom improvement.
OBJECTIVE:To compare maternal surgical and postoperative outcomes between resective-reconstructive surgery and cesarean hysterectomy in histopathologically confirmed placenta accreta spectrum, analysing patients by the initially intended surgical strategy. METHODS:We retrospectively reviewed 141 consecutive, histopathologically confirmed placenta accreta spectrum cases managed at a tertiary centre over approximately nine years (January 2017-January 2026). The primary analysis classified patients by the initially planned strategy (planned resective-reconstructive surgery, n = 84; planned hysterectomy, n = 57); six women converted to hysterectomy were analysed within the planned resective-reconstructive surgery group, and an as-treated analysis (resective-reconstructive surgery, n = 78; hysterectomy, n = 63) was pre-specified as secondary. The primary outcome was intraoperative bladder injury; estimates were adjusted for age, gravidity and depth of invasion and verified with Cochran-Mantel-Haenszel stratification. RESULTS:Hysterectomy was associated with more frequent intraoperative bladder injury (24.6% versus 8.3%; adjusted odds ratio 3.16, 95% confidence interval 1.16-8.64) and with greater transfusion requirements, longer operative time and longer postoperative stay (all p < 0.05). The bladder-injury association was consistent across accreta, increta and percreta strata (common odds ratio 3.24, 95% confidence interval 1.20-8.74). The as-treated analysis showed the same associations with larger effect sizes. CONCLUSION:In histopathologically confirmed placenta accreta spectrum, resective-reconstructive surgery was associated with lower measured maternal morbidity than hysterectomy; the association persisted, though attenuated, under the initially intended strategy and across depth-of-invasion strata. Because treatment was not randomized, these associations cannot establish superiority, and management should be individualized through multidisciplinary evaluation at experienced centres.
AIM:Anemia and obstetric hemorrhage remain major causes of maternal morbidity, transfusion exposure, and resource use. Patient Blood Management (PBM) provides a structured, patient-centered framework for optimizing red cell mass, minimizing blood loss, and applying evidence-based transfusion practice in obstetrics and gynecology. METHODS:A structured narrative review was conducted using PubMed/MEDLINE, Cochrane Library, and Scopus for English-language literature published from January 2015 to February 2026, prioritizing randomized trials, systematic reviews, consensus statements, guidelines, implementation studies, and large observational cohorts relevant to PBM in women's health. RESULTS:Current evidence supports antenatal and preoperative identification of iron deficiency, timely oral or intravenous iron therapy, early postpartum hemorrhage recognition, tranexamic acid, targeted cell salvage, viscoelastic hemostatic testing, and restrictive single-unit transfusion strategies. PBM programs have reduced blood product use in major obstetric hemorrhage from 4.18 to 0.67 units per admission and predelivery anemia from 40.3 % to 23.8 %. Population data show that transfused delivering women have high anemia and postpartum hemorrhage prevalence, while severe antenatal anemia markedly increases death or maternal near-miss risk. In gynecologic oncology, structured PBM bundles and education programs substantially reduce perioperative transfusion rates. CONCLUSION:PBM offers a structured, evidence-informed framework for obstetric and gynecologic care. Several individual components are supported by randomized trial data, whereas evidence for comprehensive PBM programs remains predominantly observational. Effective implementation requires multidisciplinary protocols, early anemia treatment, blood-conservation strategies, and disciplined transfusion thresholds, while future work should standardize implementation and measure patient-centered outcomes.
BACKGROUND:Clusterin is a multifunctional glycoprotein involved in lipid transport, complement regulation, and oxidative/inflammatory stress responses, pathways relevant to insulin resistance and metabolic stress in gestational diabetes mellitus (GDM). However, its role in established GDM remains insufficiently defined. This study aimed to compare maternal serum clusterin in established GDM and normoglycemic controls and explore associations with the need for insulin therapy and perinatal outcomes. METHODS:This prospective single-center case-control study included 88 singleton pregnancies at 24-28 weeks' gestation (44 GDM, 44 controls). Fasting serum clusterin was measured by enzyme-linked immunosorbent assay after completion of GDM screening and, in women who subsequently required insulin, before insulin initiation. RESULTS:Clusterin was lower in GDM than in controls (1.46 [0.76-2.81] vs 2.56 [1.31-3.98] ng/mL; p = 0.018). Within GDM, women who subsequently required insulin had lower clusterin than those managed with diet alone (1.14 [0.54-1.63] vs 2.26 [1.32-3.98] ng/mL; p = 0.005). In exploratory Firth penalized regression, higher clusterin remained inversely associated with the need for insulin therapy after adjustment for selected clinical and glycemic covariates (adjusted odds ratio per 1 ng/mL increase, 0.50; 95% CI 0.27-0.91; p = 0.024). Clusterin alone showed modest discrimination for GDM (AUC 0.646, 95% CI 0.537-0.745), whereas its discrimination for insulin therapy was higher but imprecise because of the small subgroup and wide confidence interval (AUC 0.748, 95% CI 0.595-0.867). Clusterin did not significantly discriminate the composite adverse perinatal outcome in either the overall cohort or the GDM subgroup. CONCLUSIONS:Maternal serum clusterin was reduced in established GDM and was associated with the subsequent need for insulin therapy, suggesting a possible link with metabolic severity. These exploratory findings are hypothesis-generating and require validation before use in treatment stratification.
