Impact and safety of pregnancy on desmoid fibromatosis management in the era of active surveillance. An international multicenter retrospective observational study.

11513 Background: Desmoid fibromatosis (DF) often occurs during pregnancy/peripartum. Guidance for planning new pregnancies during active surveillance or following DF resection has been limited. Thus, we sought to evaluate outcomes and decision making in the peripartum. Methods: Women of child-bearing age with DF diagnosed between 2000 and 2020 were interviewed about procreation decisions, in a multicenter retrospective observational study (NCT05284305). Pregnancies simultaneous or after diagnosis were analyzed. Primary outcome was DF progression/recurrence within 1 yr postpartum. Secondary outcomes were spontaneous regression, switch to active treatment, and obstetric risks. To estimate probability of progression, a random intercept logistic model was fit to account for correlation of progression in multiple pregnancies in the same patient. Results: Of 483 pts interviewed, 120 (24.8%) postponed, 32 (6.6%) interrupted, and/or 232 (48%) avoided pregnancy (in 93.3%, 50%, and 72.9% of cases because of DF), respectively. 147 pregnancies in 131 pts were concurrent with or after diagnosis: 26 (17.7%, Group A) concurrent with diagnosis, 48 (32.7%, B) after DF resection, and 73 (49.7%, C) with DF on surveillance. Estimated probability of progression was 12.0% (CI 2.0 – 48.4) during pregnancy and 15.8% (5.6 – 37.5) postpartum; for pregnancies after diagnosis (Groups B and C), these rates were 5.1% (0.4 – 40.0) and 9.0% (1.8 – 35.0). On multivariate analysis, age at pregnancy and size of primary DF were significant risk factors for progression (Table). Estimated probability of spontaneous regression was 3.6% (CI 0.2-40.7) during pregnancy and 7.1% (CI 0.3 – 67.2) postpartum. 7/38 (18.4%) spontaneously regressed after pregnancy-related PD, 4/23 (17.4%) in Groups B and C. Treatment for progression was needed in 9/79 (11.4%) postpartum, in 4/63 (6.3%) in Groups B and C. Obstetric complications were comparable to population data in developed countries. Conclusions: After DF diagnosis, pregnancy is safe with a risk of progression of 5% during pregnancy and 9% postpartum. Treatment is needed in only 6%. Spontaneous regression is less common but occurs even after initial progression. Patients decision making about procreation appeared to be influenced by their DF diagnosis. This study supports counseling that fertility options should be fully explored with expert guidance as intervention rates are low. [Table: see text]

10017 Background: Desmoid fibromatosis (DF) may be diagnosed during or after pregnancy (P). However, the risk of progression during P, or in women of child-bearing age with DF prior to P, is unknown. Furthermore, obstetric risks have not been well described. Methods: Institutional databases were reviewed at 3 sarcoma referral centers in Europe and US for women with sporadic DF from 1985 to 2011. Pregnancy and treatment data, outcomes, and obstetric complications were recorded. Results: Overall 75 women were identified. DF was diagnosed during P in 17 women (Group A) or within 6 mo after P in 10 (Group B), was in situ at the time of P in 29 women (Group C), or had been resected prior to P in 19 (Group D). Anatomic site, outcomes, and treatment for each group are in the Table. Among patients operated at diagnosis, 2/11 (18%) recurred (Group A+B). Among the entire cohort, 15 women (20%) recurred after definitive treatment and only 6 (8%) needed multiple treatments after P. Ten spontaneous regressions occurred after P (13%). Twelve women had further P following the DF-related one, and 3 (25%) needed treatment after the subsequent P. At a median follow up of 35 mo from P, 17 women did not receive any treatment (23%), and 39 remain disease-free (52%). Caesarean section was needed in 14 cases (19%), but only in 1 expressly due to DF. DF-related P was associated with abortion in 6 cases (4 spontaneous, 2 voluntary); in no case was it caused by the presence of DF. Conclusions: DF developing prior to or during P may progress during the course of P or thereafter. Spontaneous regression after P was also observed. When resected, P-related DF rarely recurs. Wait & see is an option as well. DF history is not an indication for therapeutic abortion nor a contraindication against subsequent P. [Table: see text]

Pregnancy-associated desmoid fibromatosis: A Dutch multi-centre retrospective study

P-137: Obstetric and perinatal outcomes in age matched cohorts of ovum donor recipients and in vitro fertilization patients

ABSTRACT.The COVID–19 pandemic led to local oxygen shortages worldwide. To gain a better understanding of oxygen consumption with different respiratory supportive therapies, we conducted an international multicenter observational study to determine the precise amount of oxygen consumption with high-flow nasal oxygen (HFNO) and with mechanical ventilation. A retrospective observational study was conducted in three intensive care units (ICUs) in the Netherlands and Spain. Patients were classified as HFNO patients or ventilated patients, according to the mode of oxygen supplementation with which a patient started. The primary endpoint was actual oxygen consumption; secondary endpoints were hourly and total oxygen consumption during the first two full calendar days. Of 275 patients, 147 started with HFNO and 128 with mechanical ventilation. Actual oxygen use was 4.9-fold higher in patients who started with HFNO than in patients who started with ventilation (median 14.2 [8.4–18.4] versus 2.9 [1.8–4.1] L/minute; mean difference = 11.3 [95% CI 11.0–11.6] L/minute; P < 0.01). Hourly and total oxygen consumption were 4.8-fold (P < 0.01) and 4.8-fold (P < 0.01) higher. Actual oxygen consumption, hourly oxygen consumption, and total oxygen consumption are substantially higher in patients that start with HFNO compared with patients that start with mechanical ventilation. This information may help hospitals and ICUs predicting oxygen needs during high-demand periods and could guide decisions regarding the source of distribution of medical oxygen.

Immune (Idiopathic) Thrombocytopenic Purpura (ITP): Treatment Pattern and Splenectomy Rate from a Multinational Prospective Observational Study

Data about the long-term performance of new-generation ultrathin-strut drug-eluting stents (DES) in challenging coronary lesions, such as left main (LM), bifurcation, and chronic total occlusion (CTO) lesions are scant. The international multicenter retrospective observational ULTRA study included consecutive patients treated from September 2016 to August 2021 with ultrathin-strut (<70 µm) DES in challenging de novo lesions. Primary endpoint was target lesion failure (TLF): composite of cardiac death, target-lesion revascularization (TLR), target-vessel myocardial infarction (TVMI), or definite stent thrombosis (ST). Secondary endpoints included all-cause death, acute myocardial infarction (AMI), target vessel revascularization, and TLF components. TLF predictors were assessed with Cox multivariable analysis. Of 1801 patients (age: 66.6 ± 11.2 years; male: 1410 [78.3%]), 170 (9.4%) experienced TLF during follow-up of 3.1 ± 1.4 years. In patients with LM, CTO, and bifurcation lesions, TLF rates were 13.5%, 9.9%, and 8.9%, respectively. Overall, 160 (8.9%) patients died (74 [4.1%]from cardiac causes). AMI and TVMI rates were 6.0% and 3.2%, respectively. ST occurred in 11 (1.1%) patients while 77 (4.3%) underwent TLR. Multivariable analysis identified the following predictors of TLF: age, STEMI with cardiogenic shock, impaired left ventricular ejection fraction, diabetes, and renal dysfunction. Among the procedural variables, total stent length increased TLF risk (HR: 1.01, 95%CI: 1-1.02 per mm increase), while intracoronary imaging reduced the risk substantially (HR: 0.35, 95%CI: 0.12-0.82). Ultrathin-strut DES showed high efficacy and satisfactory safety, even in patients with challenging coronary lesions. Yet, despite using contemporary gold-standard DES, the association persisted between established patient- and procedure-related features of risk and impaired 3-year clinical outcome.

Objectives: The objective of this study is to evaluate obstetric outcomes in women with heart disease and determine whether current multidisciplinary management approaches adversely affect the mother, the neonate, or both. Also to compare the accuracy of several risk scores (RS) including the modified World Health Organization classification (mWHO) and CARPREG to predict obstetric and neonatal complications and to study the addition value of Uteroplacental-Doppler flow (UDF) parameters to predict obstetric complications. Methods: A prospective cohort study examined outcomes in women with heart disease (HD), the majority of whom had corrective surgery and delivered between January 2007 and March 2012. Results: One hundred and seventy-four patients with 179 pregnancies were included in the study. Obstetric complications, including premature labor, arose in 87 patients (48.6%). Neonatal complications were observed in 11 cases (7%). On multivariate analysis, maternal heart disease was predictive of adverse perinatal events (46 cases, 25.7%) and mode of delivery (Thierry’s spatula) of third- or fourth-degree perineal tears (six cases, 3.2%). mWHO classification predicted obstetric complications (p = 0.0001) better than the CARPREG study. Impaired UDF (uterine artery pulsatility index-20 weeks and umbilical artery pulsatility index-32 weeks in HD versus healthy women: 20w 1.12 versus 1.34, p = 0.005; 32w 0.87 versus 1.09, p = 0.008) was associated with adverse obstetric and offspring outcome in the group of HD pregnant women. Conclusions: Nearly 50% of pregnancies were associated with an adverse obstetric outcome, particularly IUGR. mWHO was better at predicting obstetric and neonatal complications that CARPREG in all cathegories. Furthermore, compromised UDF combined with mWHO improved the prediction of obstetric and offspring complications in this population.

1078 Background: The emergence of novel therapeutic agents demonstrating improved progression-free survival (PFS) and overall survival (OS) in breast cancer patients with low HER2 expression underscores the need for accurate and reproducible HER2 status assessment. However, challenges such as subjective interpretation of immunohistochemistry (IHC) staining and variability in assay quality hinder diagnostic consistency. AI-based decision support software could enhance diagnostic accuracy and reproducibility. To date, systematic evaluation of pathologist performance in scoring low HER2 expression, as well as the role of AI assistance, remains limited in real-world, multicenter settings. Methods: Six academic centers from different countries provided digital HER2 IHC-stained breast cancer images (n = 728) generated with five whole-slide scanner models and one microscope camera. In a two-arm observational study, consensus ground truth (GT) scores were established by two expert pathologists per center without AI assistance. Subsequently, two additional pathologists (scorers) evaluated each case both without and with AI support. Scoring followed ASCO/CAP 2023 HER2 interpretation guidelines, with an additional subclassification of IHC 0 cases into "null" (IHC 0 with no staining) and "ultralow" (IHC 0 with membrane staining). Results: For the HER2-low decision range, AI software alone achieved 91.0% accuracy in distinguishing HER2 0 from 1+/2+/3+ scores against GT. Across the four categories, AI achieved 80.3% accuracy compared to 77.6% for scorers alone and 81.4% with AI assistance. AI support improved inter-reader agreement from 73.5% to 86.4%. When the HER2 ultralow category was included, AI assistance increased scorers' average accuracy across all classes from 70.4% to 74.7% and boosted inter-reader agreement from 65.6% to 80.6%. For differentiating HER2 null from HER2 ultralow, AI improved scorers' accuracy from 68.6% to 77.9%, resulting in 40% more cases being classified as HER2 ultralow and 65% reduction in the number of incorrectly scored HER2 null cases. Conclusions: This first international multicenter study on HER2 IHC diagnosis, including HER2 ultralow scoring highlights the challenges faced by pathologists and the significant benefits of AI decision-support systems in real-world settings. AI assistance improved pathologist concordance and accuracy, particularly at the HER2 null vs. ultralow boundary, reducing diagnostic errors. Incorporating AI into routine clinical diagnostics has the potential to optimize treatment selection for breast cancer patients.

PurposeTo analyze the application of a lung ultrasound (LUS)-based diagnostic approach to patients suspected of COVID-19, combining the LUS likelihood of COVID-19 pneumonia with patient’s symptoms and clinical history.MethodsThis is an international multicenter observational study in 20 US and European hospitals. Patients suspected of COVID-19 were tested with reverse transcription-polymerase chain reaction (RT-PCR) swab test and had an LUS examination. We identified three clinical phenotypes based on pre-existing chronic diseases (mixed phenotype), and on the presence (severe phenotype) or absence (mild phenotype) of signs and/or symptoms of respiratory failure at presentation. We defined the LUS likelihood of COVID-19 pneumonia according to four different patterns: high (HighLUS), intermediate (IntLUS), alternative (AltLUS), and low (LowLUS) probability. The combination of patterns and phenotypes with RT-PCR results was described and analyzed.ResultsWe studied 1462 patients, classified in mild (n = 400), severe (n = 727), and mixed (n = 335) phenotypes. HighLUS and IntLUS showed an overall sensitivity of 90.2% (95% CI 88.23–91.97%) in identifying patients with positive RT-PCR, with higher values in the mixed (94.7%) and severe phenotype (97.1%), and even higher in those patients with objective respiratory failure (99.3%). The HighLUS showed a specificity of 88.8% (CI 85.55–91.65%) that was higher in the mild phenotype (94.4%; CI 90.0–97.0%). At multivariate analysis, the HighLUS was a strong independent predictor of RT-PCR positivity (odds ratio 4.2, confidence interval 2.6–6.7, p < 0.0001).ConclusionCombining LUS patterns of probability with clinical phenotypes at presentation can rapidly identify those patients with or without COVID-19 pneumonia at bedside. This approach could support and expedite patients’ management during a pandemic surge.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-021-06373-7.

The Tokyo Guidelines 2007 (TG07) first presented the diagnostic and severity grading criteria for acute cholangitis. Subsequently updated in 2013, the Tokyo Guidelines (TG13) have been widely adopted throughout the world as global standard guidelines. We set out to verify the efficacy of these TG13 criteria in an international multicenter study. We reviewed 6,063 patients who were clinically diagnosed with acute cholangitis in Japan and Taiwan over a 2-year period. The TG13 diagnostic and severity grading criteria were retrospectively applied, and 30-day mortality was investigated. A diagnosis of acute cholangitis was made in 5,454 (90.0%) patients on the basis of the TG13 criteria, and in 4,815 (79.4%) patients on the basis of the TG07 criteria. The 30-day mortality rates of patients with Grade III, Grade II, and Grade I were 5.1%, 2.6%, and 1.2%, respectively, and increased significantly along with disease severity. The mortality rate in the 1,272 Grade II cases where urgent or early biliary drainage was performed was 2.0% (n = 25), which was significantly lower than that of 3.7% (n = 28) in the other 748 cases. By using the TG13 diagnostic and severity grading criteria, more patients with possible acute cholangitis can be diagnosed, and patients whose prognosis can potentially be improved by early biliary drainage can be identified. The TG13 criteria are appropriate and useful for clinical practice.

2022-RA-598-ESGO Prognostic factors for adverse obstetric outcomes in pregnant cancer patients an update on 2174 cases registered in the INCIP registry

The ability to pursue family planning goals is integral to gender equity in any field. Procedural specialties pose occupational risks to pregnancy. As the largest procedural specialty, general surgery provides an opportunity to understand family planning, workplace support for parenthood, obstetric outcomes, and the impact of these factors on workforce well-being, gender equity, and attrition. To examine pregnancy and parenthood experiences, including mistreatment and obstetric outcomes, among a cohort of US general surgical residents. This cohort study involved a cross-sectional national survey of general surgery residents in all programs accredited by the Accreditation Council for Graduate Medical Education after the 2021 American Board of Surgery In-Training Examination. Female respondents who reported a pregnancy and male respondents whose partners were pregnant during clinical training were queried about pregnancy- and parenthood-based mistreatment, obstetric outcomes, and current well-being (burnout, thoughts of attrition, suicidality). Primary outcomes included obstetric complications and postpartum depression compared between female residents and partners of male residents. Secondary outcomes included perceptions about support for family planning, pregnancy, or parenthood; assisted reproductive technology use; pregnancy/parenthood-based mistreatment; neonatal complications; and well-being, compared between female and male residents. A total of 5692 residents from 325 US general surgery programs participated (81.2% response rate). Among them, 957 residents (16.8%) reported a pregnancy during clinical training (692/3097 [22.3%] male vs 265/2595 [10.2%] female; P < .001). Compared with male residents, female residents more frequently delayed having children because of training (1201/2568 [46.8%] females vs 1006/3072 [32.7%] males; P < .001) and experienced pregnancy/parenthood-based mistreatment (132 [58.1%] females vs 179 [30.5%] males; P < .001). Compared with partners of male residents, female residents were more likely to experience obstetric complications (odds ratio [OR], 1.42; 95% CI, 1.04-1.96) and postpartum depression (OR, 1.63; 95% CI, 1.11-2.40). Pregnancy/parenthood-based mistreatment was associated with increased burnout (OR, 2.03; 95% CI, 1.48-2.78) and thoughts of attrition (OR, 2.50; 95% CI, 1.61-3.88). Postpartum depression, whether in female residents or partners of male residents, was associated with resident burnout (OR, 1.93; 95% CI, 1.27-2.92), thoughts of attrition (OR, 2.32; 95% CI, 1.36-3.96), and suicidality (OR, 5.58; 95% CI, 2.59-11.99). This study found that pregnancy/parenthood-based mistreatment, obstetric complications, and postpartum depression were associated with female gender, likely driving gendered attrition. Systematic change is needed to protect maternal-fetal health and advance gender equity in procedural fields.

Background:Classified by the WHO as one of the 19 most dangerous fungal pathogens, Pneumocystis jirovecii has been associated with increasing outbreaks of Pneumocystis pneumonia (PCP) among solid organ transplant (SOT) recipients worldwide. Mycophenolic acid (MPA), an inosine monophosphate dehydrogenase (IMPDH) inhibitor commonly used as an immunosuppressant to prevent organ rejection, is a risk factor for PCP. However, MPA also displays antifungal activity, potentially protecting against PCP, despite not being used to treat it. Therefore the underlying factors driving these outbreaks remain undefined.Methods:In this international multicenter retrospective observational study, P. jirovecii samples were collected from 96 SOT patients (including 94 from nine separate outbreaks and 84 on MPA therapy) and 67 non-transplant controls (none on MPA), between 1986 and 2020 across six countries in Europe, North America and Asia. All samples underwent extensive targeted sequencing of the P. jirovecii inosine monophosphate dehydrogenase (impdh) gene and multiple genetic markers, with selected samples further analyzed for complete mitogenome and restriction fragment length polymorphisms. Computational modeling was employed to predict the effects of IMPDH mutations on protein structure and MPA binding.Results:Six impdh mutations (including one previously reported) were identified, with frequencies of 4–21% each in SOT patients and 0–1% in controls. These mutations were strongly associated with prior MPA exposure and showed marked geographic segregation and temporal shifts. Four mutations were each linked to multiple distinct genotype profiles, representing separate P. jirovecii strains. Structure modeling predicted that these four mutations reduced protein stability and binding affinity to MPA.Conclusions:This study suggests that the widespread use of MPA in SOT recipients has unexpectedly driven the emergence of multiple impdh mutations in P. jirovecii, each presumably arising independently in multiple strains worldwide. These mutations likely confer drug resistance and provide a selective survival advantage to P. jirovecii in SOT recipients exposed to MPA, thereby facilitating transmission and outbreaks. These findings have significant implications for the prevention and clinical management of PCP in SOT recipients, highlighting a rare example of how antimicrobial resistance can emerge through unexpected pathways, transcending conventional antimicrobial use and emphasizing the need for increased vigilance and strategic adaptation in clinical practice.

There is great degree of interobserver variability in the visual angiographic assessment of left main coronary disease (LMCD). Fractional flow reserve and intravascular ultrasound are often used in this setting. The use of instantaneous wave-free ratio (iFR) for evaluation of LMCD has not been well studied. The aim of this study is to evaluate the use of iFR in the assessment of angiographically intermediate LMCD. This is an international multicenter retrospective observational study of patients who underwent both iFR and intravascular ultrasound evaluation for angiographically intermediate LMCD. An independent core laboratory performed blinded off-line analysis of all intravascular ultrasound data. A minimum lumen area of 6 mm2 was used as the cutoff for significant disease. One hundred twenty-five patients (mean age, 68.4±9.5 years, 84.8% male) were included in this analysis. Receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm2 with an area under the curve of 0.77 (77% sensitivity, 66% specificity; P<0.0001). Among the 69 patients without ostial left anterior descending artery or left circumflex artery disease, receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm2 with an area under the curve of 0.84 (70% sensitivity, 84% specificity; P<0.0001). The correlation was not significantly different when the body surface area was considered. In this study, in patients with intermediate LMCD, iFR of ≤0.89 correlates with intravascular ultrasound minimum lumen area <6 mm2 regardless of body surface area. The current study supports the use of iFR for the evaluation of intermediate LMCD.