The largest single center report on intravenous leiomyomatosis and development of a classification to guide surgical management.

BACKGROUND: Intravenous leiomyomatosis (IVL) is a rare neoplasm, the accumulated knowledge about the characteristics and prognosis of this tumor has been derived mainly from isolated case reports with no comprehensive research. In this study, we reviewed our institution's experience with IVL over a 20-year period and developed a classification system that can be used to guide surgical management. MATERIALS AND METHODS: The study had a retrospective cohort design and included patients who underwent resection of IVL at our institution between January 2002 and December 2022. Perioperative parameters were then collected among 4 stages of our proposed classification. The long-term outcomes, oncologic prognosis, and factors associated with recurrence were analyzed. RESULTS: A total of 216 patients were included (stage 1, n=92; stage 2, n=39; stage 3, n=76; stage 4, n=9). The mean follow-up duration was 26.34 months, during which 18 patients (9.7%) in the complete resection group had recurrence, and 12 (39.0%) in the incomplete resection group showed disease progression. Recurrence or progression of residual disease was associated with adjuvant aromatase inhibitor therapy and maximum tumor thrombus diameter but not with total hysterectomy and bilateral salpingo-oophorectomy, age, or postoperative treatment with a gonadotropin-releasing hormone agonist therapy. CONCLUSIONS: This is the largest single-center report on IVL published to date and provides valuable information on its clinical features and long-term outcomes as well as surgical technique. Our classification system can be used to evaluate the extent of lesion involvement and guide surgical management.

Risk of postpartum hemorrhage with increasing first stage labor duration.

With increasing rates of postpartum hemorrhage (PPH) in high-income countries, an important clinical concern is the impact of labor duration on the risk of PPH. This study examined the relationship between increasing active first stage labor duration and PPH and explored the role of second stage labor duration and cesarean delivery (CD) in this association. Including 77,690 nulliparous women with spontaneous labor onset, first stage labor duration was defined as the time from 5 cm to 10 cm, second stage duration from 10 cm dilation to birth and PPH as estimated blood loss > 1000 ml. Using modified Poisson regression for risk ratios (RR) and confidence intervals (CI), we found a 1.5-fold (RR, 1.53; 95% CI, 1.41‒1.66) increased PPH risk when first stage of labor exceeded 12.1 h compared to the reference (< 7.7 h). Mediation analysis showed that 18.5% (95% CI, 9.7‒29.6) of the increased PPH risk with a prolonged first stage (≥ 7.7 h) was due to a prolonged second stage (> 3 h) or CD. These results suggest that including first stage duration in intrapartum assessments could improve PPH risk identification in first-time mothers with a singleton fetus in vertex presentation at full term with spontaneous labor onset.

Differential effects of inosine monophosphate dehydrogenase (IMPDH/GuaB) inhibition in Acinetobacter baumannii and Escherichia coli.

Inosine 5'-monophosphate dehydrogenase (IMPDH), known as GuaB in bacteria, catalyzes the rate-limiting step in de novo guanine biosynthesis and is conserved from humans to bacteria. We developed a series of potent inhibitors that selectively target GuaB over its human homolog. Here, we show that these GuaB inhibitors are bactericidal, generate phenotypic signatures that are distinct from other antibiotics, and elicit different time-kill kinetics and regulatory responses in two important Gram-negative pathogens: Acinetobacter baumannii and Escherichia coli. Specifically, the GuaB inhibitor G6 rapidly kills A. baumannii but only kills E. coli after 24 h. After exposure to G6, the expression of genes involved in purine biosynthesis and stress responses change in opposite directions while siderophore biosynthesis is downregulated in both species. Our results suggest that different species respond to GuaB inhibition using distinct regulatory programs and possibly explain the different bactericidal kinetics upon GuaB inhibition. The comparison highlights opportunities for developing GuaB inhibitors as novel antibiotics.IMPORTANCEA. baumannii is a priority bacterial pathogen for which development of new antibiotics is urgently needed due to the emergence of multidrug resistance. We recently developed a series of specific inhibitors against GuaB, a bacterial inosine 5'-monophosphate dehydrogenase, and achieved sub-micromolar minimum inhibitory concentrations against A. baumannii. GuaB catalyzes the rate-limiting step of de novo guanine biosynthesis and is highly conserved across bacterial pathogens. This study shows that inhibition of GuaB induced a bacterial morphological profile distinct from that of other classes of antibiotics, highlighting a novel mechanism of action. Moreover, our transcriptomic analysis showed that regulation of de novo purine biosynthesis and stress responses of A. baumannii upon GuaB inhibition differed significantly from that of E. coli.

Discovery of GuaB inhibitors with efficacy against Acinetobacter baumannii infection.

Guanine nucleotides are required for growth and viability of cells due to their structural role in DNA and RNA, and their regulatory roles in translation, signal transduction, and cell division. The natural antibiotic mycophenolic acid (MPA) targets the rate-limiting step in de novo guanine nucleotide biosynthesis executed by inosine-5´-monophosphate dehydrogenase (IMPDH). MPA is used clinically as an immunosuppressant, but whether in vivo inhibition of bacterial IMPDH (GuaB) is a valid antibacterial strategy is controversial. Here, we describe the discovery of extremely potent small molecule GuaB inhibitors (GuaBi) specific to pathogenic bacteria with a low frequency of on-target spontaneous resistance and bactericidal efficacy in vivo against Acinetobacter baumannii mouse models of infection. The spectrum of GuaBi activity includes multidrug-resistant pathogens that are a critical priority of new antibiotic development. Co-crystal structures of A. baumannii, Staphylococcus aureus, and Escherichia coli GuaB proteins bound to inhibitors show comparable binding modes of GuaBi across species and identifies key binding site residues that are predictive of whole-cell activity across both Gram-positive and Gram-negative clades of Bacteria. The clear in vivo efficacy of these small molecule GuaB inhibitors in a model of A. baumannii infection validates GuaB as an essential antibiotic target. IMPORTANCE: The emergence of multidrug-resistant bacteria worldwide has renewed interest in discovering antibiotics with novel mechanism of action. For the first time ever, we demonstrate that pharmacological inhibition of de novo guanine biosynthesis is bactericidal in a mouse model of Acinetobacter baumannii infection. Structural analyses of novel inhibitors explain differences in biochemical and whole-cell activity across bacterial clades and underscore why this discovery may have broad translational impact on treatment of the most recalcitrant bacterial infections.

A population-based study on trajectories of HER2 status during neoadjuvant chemotherapy for early breast cancer and metastatic progression.

BACKGROUND: This study aimed to investigate the distribution and changes of HER2 status in untreated tumours, in residual disease and in metastasis, and their long-term prognostic implications. METHODS: This is a population-based cohort study of patients treated with neoadjuvant chemotherapy for breast cancer during 2007-2020 in the Stockholm-Gotland region which comprises 25% of the entire Swedish population. Information was extracted from the National Breast Cancer Registry and electronic patient charts to minimize data missingness and misclassification. RESULTS: In total, 2494 patients received neoadjuvant chemotherapy, of which 2309 had available pretreatment HER2 status. Discordance rates were 29.9% between primary and residual disease (kappa = 0.534), 31.2% between primary tumour and metastasis (kappa = 0.512) and 33.3% between residual disease to metastasis (kappa = 0.483). Adjusted survival curves differed between primary HER2 0 and HER2-low disease (p < 0.001), with the former exhibiting an early peak in risk for death which eventually declined below the risk of HER2-low. Across all disease settings, increasing the number of biopsies increased the likelihood of detecting HER2-low status. CONCLUSION: HER2 status changes during neoadjuvant chemotherapy and metastatic progression, and the long-term behaviours of HER2 0 and HER2-low disease differ, underscoring the need for obtaining tissue biopsies and for extended follow-up in breast cancer studies.

Midwifery continuity of care, breastfeeding and neonatal hyperbilirubinemia: A retrospective cohort study.

AIM: To examine the association between Midwifery Continuity of Care (MCoC) and exclusive breastfeeding at hospital discharge and neonatal hyperbilirubinemia. METHODS: A matched cohort design was employed using data from the Swedish Pregnancy Register. The study included 12,096 women who gave birth at a university hospital in Stockholm, Sweden from January 2019 to August 2021. Women and newborns cared for in a MCoC model were compared with a propensity-score matched set receiving standard care. Risk ratios (RR) were determined with 95 % confidence intervals (CI) based on the matched cohort through modified Poisson regressions with robust standard error. A mediation analysis assessed the direct and indirect effects of MCoC on exclusive breastfeeding at hospital discharge and neonatal hyperbilirubinemia and to what extent the association was mediated by preterm birth. FINDING: Findings showed that MCoC was associated with a higher chance of exclusive breastfeeding rate (RR: 1.06, 95 % CI: 1.01-1.12) and lower risk of neonatal hyperbilirubinemia (RR: 0.51, 95 % CI: 0.32-0.82) compared with standard care. Mediation analysis demonstrated that lower preterm birth accounted for approximately 28 % of total effect on the reduced risk of neonatal hyperbilirubinemia. DISCUSSION/CONCLUSION: This matched cohort study provided preliminary evidence that MCoC models could be an intervention for improving exclusive breastfeeding rates at hospital discharge and reducing the risk of neonatal hyperbilirubinemia.

Mapping the awareness and knowledge about patient and public versions of guidelines among stakeholders in China: a cross-sectional survey.

OBJECTIVES: Patient and public versions of guidelines (PVGs) have gradually gained wide recognition and attention from the public and the society due to their scientific, professional, and authoritative characteristics. This study aims to survey the awareness and knowledge of PVGs among stakeholders in China. STUDY DESIGN AND SETTING: This was a cross-sectional survey among stakeholders (guideline developers, clinicians, journal editors, patients, and the public) in China. We self-designed the questionnaire and distributed it through the Questionnaire Star platform. The primary outcomes were awareness of PVGs and opinions about the development methodology, writing, dissemination, and implementation of PVGs. The Kruskal-Wallis H test and post hoc multiple comparison tests were used to compare the levels of awareness of PVGs between different subgroups of respondents. RESULTS: A total of 1319 valid questionnaires were collected: 722 from guideline developers, 136 from clinicians, 83 from journal editors, 284 from patients, and 94 from members of the public. Of all respondents, 253 (19.2%) had not heard of PVGs, 349 (26.5%) had heard of PVGs but had no further knowledge, 475 (36.0%) had some knowledge of PVGs, and 242 (18.3%) were familiar with or had participated in the development of PVGs. Guideline developers, clinicians, and journal editors had higher awareness than patients and the public. Higher education and older age also correlated with higher awareness of PVGs. More than half (52.9%) of guideline developers considered that both rewriting of the source guidelines and direct development as independent documents were appropriate methods for developing PVGs. The survey respondents agreed that clinicians (97.3%), guideline methodologists (76.6%), representatives of patients and the public (74.5%), and medical editors or writers (63.4%) should participate in the development of PVGs. More than 80% of the respondents agreed that the quality of evidence and strength of recommendations should be presented; however, there was no consensus in the form of presentation. CONCLUSIONS: The level of awareness of PVGs among stakeholders in China is relatively low and differs between different stakeholder groups, but the majority of key stakeholders have a positive attitude toward PVGs. The collection of the perspectives and opinions on the development methods, writing, dissemination, and implementation provides a key reference and basis for the future optimization and improvement of PVGs development.

Longitudinal molecular profiling elucidates immunometabolism dynamics in breast cancer.

Although metabolic reprogramming within tumor cells and tumor microenvironment (TME) is well described in breast cancer, little is known about how the interplay of immune state and cancer metabolism evolves during treatment. Here, we characterize the immunometabolic profiles of tumor tissue samples longitudinally collected from individuals with breast cancer before, during and after neoadjuvant chemotherapy (NAC) using proteomics, genomics and histopathology. We show that the pre-, on-treatment and dynamic changes of the immune state, tumor metabolic proteins and tumor cell gene expression profiling-based metabolic phenotype are associated with treatment response. Single-cell/nucleus RNA sequencing revealed distinct tumor and immune cell states in metabolism between cold and hot tumors. Potential drivers of NAC based on above analyses were validated in vitro. In summary, the study shows that the interaction of tumor-intrinsic metabolic states and TME is associated with treatment outcome, supporting the concept of targeting tumor metabolism for immunoregulation.

Comprehensive evaluation of the water-fertilizer coupling effects on pumpkin under different irrigation volumes.

Compared to conventional irrigation and fertilization, the Water-fertilizer coupling can significantly enhance the efficiency of water and fertilizer utilization, thereby promoting crop growth and increasing yield. Targeting the challenges of poor crop growth, low yield, and inefficient water and fertilizer utilization in the arid region of northwest China under conventional irrigation and fertilization practices. Therefore, a two-year on-farm experiment in 2022 and 2023 was conducted to study the effects of water-fertilizer coupling regulation on pumpkin growth, yield, water consumption (ET), and water and fertilizer use efficiency. Simultaneously the comprehensive evaluation of multiple objectives was carried out using principal component analysis (PCA) methods, so as to propose an suitable water-fertilizer coupling regulation scheme for the region. The experiment was set up as a two-factor trial using water-fertilizer integration technology under three irrigation volume (W1 = 37.5 mm, W2 = 45.5 mm, W3 = 52.5mm) and three organic fertilizer application amounts (F1 = 3900-300 kg ha-1, F2 = 4800-450 kg·ha-1, F3 = 5700-600 kg·ha-1), with the traditional irrigation and fertilization scheme from local farmers as control treatments (CK). The results indicated that irrigation volume and organic fertilizer application significantly affected pumpkin growth, yield, and water and fertilizer use efficiency (P<0.05). Pumpkin yield increased with increasing irrigation volume. Increasing organic fertilizer levels within a certain range benefited pumpkin plant growth, dry matter accumulation, and yield, however, excessive application beyond a certain level had inhibited effects on those. The increased fertilizer application under the same irrigation volume enhanced the efficiency of water and fertilizer utilization. However excessive irrigation only resulted in inefficient water consumption, reducing the water and fertilizer use efficiency. The Comprehensive evaluation by PCA revealed that the F2W3 treatment outperformed all the others, effectively addressing the triple objectives of increasing production, improving efficiency, and promoting green production. Therefore, F2W3 (Irrigation volume: 52.5 mm; Fertilizer application amounts: 4800-450 kg/ha-1) as a water and fertilizer management scheme for efficient pumpkin production in the arid region of northwest China.

Human Leukocyte Antigen Signatures as Pathophysiological Discriminants of Microscopic Colitis Subtypes.

BACKGROUND AND AIMS: Microscopic colitis [MC] is currently regarded as an inflammatory bowel disease that manifests as two subtypes: collagenous colitis [CC] and lymphocytic colitis [LC]. Whether these represent a clinical continuum or distinct entities is, however, an open question. Genetic investigations may contribute important insight into their respective pathophysiologies. METHODS: We conducted a genome-wide association study [GWAS] meta-analysis in 1498 CC, 373 LC patients, and 13 487 controls from Europe and the USA, combined with publicly available MC GWAS data from UK Biobank and FinnGen [2599 MC cases and 552 343 controls in total]. Human leukocyte antigen [HLA] alleles and polymorphic residues were imputed and tested for association, including conditional analyses for the identification of key causative variants and residues. Genetic correlations with other traits and diagnoses were also studied. RESULTS: We detected strong HLA association with CC, and conditional analyses highlighted the DRB1*03:01 allele and its residues Y26, N77, and R74 as key to this association (best p = 1.4 × 10-23, odds ratio [OR] = 1.96). Nominally significant genetic correlations were detected between CC and pneumonia [rg = 0.77; p = 0.048] and oesophageal diseases [rg = 0.45, p = 0.023]. An additional locus was identified in MC GWAS analyses near the CLEC16A and RMI2 genes on chromosome 16 [rs35099084, p = 2.0 × 10-8, OR = 1.31]. No significant association was detected for LC. CONCLUSION: Our results suggest CC and LC have distinct pathophysiological underpinnings, characterised by an HLA predisposing role only in CC. This challenges existing classifications, eventually calling for a re-evaluation of the utility of MC umbrella definitions.

Duration of the active first stage of labour and severe perineal lacerations and maternal postpartum complications: a population-based cohort study.

OBJECTIVE: The impact of first stage labour duration on maternal outcomes is sparsely investigated. We aimed to study the association between a longer active first stage and maternal complications in the early postpartum period. DESIGN: A population-based cohort study. SETTING: Regions of Stockholm and Gotland, Sweden, 2008-2020. POPULATION: A cohort of 159 459 term, singleton, vertex pregnancies, stratified by parity groups. METHODS: The exposure was active first stage duration, categorised in percentiles. Poisson regression analysis was performed to estimate the adjusted relative risk (aRR) and the 95% confidence interval (95% CI). To investigate the effect of second stage duration on the outcome, mediation analysis was performed. MAIN OUTCOME MEASURES: Severe perineal lacerations (third or fourth degree), postpartum infection, urinary retention and haematoma in the birth canal or ruptured sutures. RESULTS: The risks of severe perineal laceration, postpartum infection and urinary retention increased with a longer active first stage, both overall and stratified by parity group. The aRR increased with a longer active first stage, using duration of <50th percentile as the reference. In the ≥90th percentile category, the aRR for postpartum infection was 1.64 (95% CI 1.46-1.84) in primiparous women, 2.43 (95% CI 1.98-2.98) in parous women with no previous caesarean delivery (CD) and 2.33 (95% CI 1.65-3.28) in parous women with a previous CD. The proportion mediated by second stage duration was 33.4% to 36.9% for the different outcomes in primiparous women. The risk of haematoma or ruptured sutures did not increased with a longer active first stage. CONCLUSIONS: Increasing active first stage duration is associated with maternal complications in the early postpartum period.

Co-Occurrence of Sensorineural Hearing Loss and Congenital Heart Disease: Etiologies and Management.

OBJECTIVES/HYPOTHESIS: The co-occurrence of sensorineural hearing loss (SNHL) and congenital heart disease (CHD) is a rare condition with complex etiologies. The purpose of this study is to assess the etiologies, clinical features, and outcomes of cochlear implant (CI) in this patient population. STUDY DESIGN: Case series and literature review. METHODS: Clinical data of children who were diagnosed with SNHL and CHD and received CIs at a tertiary hospital from 2016 to 2021 were retrospectively analyzed. A literature review was performed to identify patients with SNHL and CHD. FINDINGS: Of the 382 children who underwent cochlear implantation at our center, eight (2.1%) were diagnosed with SNHL and CHD. A literature review identified 1525 patients from 254 studies; the database therefore consisted of 1533 patients. The most common genetic etiologies of co-occurring SNHL and CHD were CHARGE syndrome (36.3%), Turner syndrome (8.4%), 22q11.2 deletion (3.0%), Noonan syndrome (2.9%), and Down syndrome (2.5%), whereas the most common non-genetic etiologies were congenital rubella syndrome (22.9%) and SNHL after early cardiac surgery (5.5%). Most of the patients presented with congenital, bilateral, severe-profound SNHL requiring early rehabilitation. Of the 126 children who received CIs at a median age of 2.5 years, half showed delayed speech development at last follow-up. CONCLUSIONS: Co-occurring SNHL and CHD is a rare condition with complex etiologies. Timely hearing intervention with long-term follow-up and proper timing of heart surgery is essential for these children. LEVEL OF EVIDENCE: 4, case series Laryngoscope, 134:400-409, 2024.

Heavy metal contamination impacts the structure and co-occurrence patterns of bacterial communities in agricultural soils.

Heavy metal (HM) contamination caused by mining and smelting activities can be harmful to soil microbiota, which are highly sensitive to HM stress. Here, we explore the effects of HM contamination on the taxonomic composition, predicted function, and co-occurrence patterns of soil bacterial communities in two agricultural fields with contrasting levels of soil HMs (i.e., contaminated and uncontaminated natural areas). Our results indicate that HM contamination does not significantly influence soil bacterial α diversity but changes the bacterial community composition by enriching the phyla Gemmatimonadetes, Planctomycetes, and Parcubacteria and reducing the relative abundance of Actinobacteria. Our results further demonstrate that HM contamination can strengthen the complexity and modularity of the bacterial co-occurrence network but weaken positive interactions between keystone taxa, leading to the gradual disappearance of some taxa that originally played an important role in healthy soil, thereby possibly reducing the resistance of bacterial communities to HM toxicity. The predicted functions of bacterial communities are related to membrane transport, amino acid metabolism, energy metabolism, and carbohydrate metabolism. Among these, functions related to HM detoxification and antioxidation are enriched in uncontaminated soils, while HM contamination enriches functions related to metal resistance. This study demonstrated that microorganisms adapt to the stress of HM pollution by adjusting their composition and enhancing their network complexity and potential ecological functions.

Fermentation, functional analysis, and biological activities of turmeric kombucha.

BACKGROUND: Kombucha is a popular fermented drink with therapeutic benefits. The present study aimed to examine the fermentation of turmeric-infused kombucha and evaluate its biological activities and functional properties. RESULTS: The study of pH dynamics during fermentation found that turmeric kombucha has a lower pH decrease than standard kombucha, with the lowest pH of 3.1 being observed in 0.1% turmeric kombucha and the maximum pH of 3.8 found in 1% turmeric kombucha. The research shows that the symbiotic consortia of bacteria and yeast alters during the fermentation process with turmeric. Gas chromatogrphy-mass spectrometry analysis revealed that turmeric kombucha is abundant in terpenes, ketones, alcohols, aldehydes, phenols and fatty acids, with higher levels of active ingredients than regular kombucha. The kombucha with 0.6% turmeric had the highest overall acceptance score (9.0) in sensory evaluation. The total phenolic content after fermentation was in the range 0.2-0.8 mg gallic acid equivalents mL-1 . Increasing turmeric concentrations increased the antioxidant, cytotoxic and antibacterial activity of kombucha analogs, with the highest antioxidant activity (89%) observed at 0.8% turmeric, and the maximum cytotoxicity (74%) and antibacterial activity (zones of inhibition of 17.7 and 15.9 mm against Staphylococcus aureus and Escherichia coli, respectively) observed at 1% turmeric. CONCLUSION: The fermentation of kombucha infused with turmeric enhanced its biological activities, making it a healthier alternative to traditional kombucha and presenting new opportunities in the field of functional foods. Further investigations into the mechanisms underlying these effects and in vivo studies are warranted to fully comprehend the impact of turmeric kombucha consumption on human health. © 2023 Society of Chemical Industry.

Effects of long-term metal exposure on the structure and co-occurrence patterns of the oral microbiota of residents around a mining area.

Objectives: The aim of our study was to investigate the impact of long-term exposure to heavy metals on the microbiome of the buccal mucosa, to unveil the link between environmental contamination and the oral microbial ecosystem, and to comprehend its potential health implications. Methods: Subjects were divided into two groups: the exposure group and the control group. We collected samples of buccal mucosa, soil, and blood, and conducted microbial diversity analysis on both groups of oral samples using 16S rRNA gene sequencing. The concentrations of heavy metals in blood and soil samples were also determined. Additionally, microbial networks were constructed for the purpose of topological analysis. Results: Due to long-term exposure to heavy metals, the relative abundance of Rhodococcus, Delftia, Fusobacterium, and Peptostreptococcus increased, while the abundance of Streptococcus, Gemella, Prevotella, Granulicatella, and Porphyromonas decreased. The concentrations of heavy metals in the blood (Pb, Cd, Hg, and Mo) were associated with the growth of Rhodococcus, Delftia, Porphyromonas, and Gemella. In addition, the relative abundances of some pathogenic bacteria, such as Streptococcus anginosus, S. gordonii, and S. mutans, were found to be enriched in the exposure group. Compared to the exposure group network, the control group network had a greater number of nodes, modules, interactive species, and keystone taxa. Module hubs and connectors in the control group converted into peripherals in the exposure group, indicating that keystone taxa changed. Metals in the blood (Pb, Cd, Hg, and Mo) were drivers of the microbial network of the buccal mucosa, which can have adverse effects on the network, thus providing conditions for the occurrence of certain diseases. Conclusion: Long-term exposure to multiple metals perturbs normal bacterial communities in the buccal mucosa of residents in contaminated areas. This exposure reduces the complexity and stability of the microbial network and increases the risk of developing various diseases.

Diagnosis, Genetics, and Management of 24 Patients With Cardiac Paragangliomas: Experience From a Single Center.

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.

First stage of labour duration and associated risk of adverse neonatal outcomes.

Prior evidence evaluating the benefits and harms of expectant labour duration during active first stage is inconclusive regarding potential consequences for the neonate. Population-based cohort study in Stockholm-Gotland region, Sweden, including 46,040 women (Robson 1), between October 1st, 2008 and June 15th, 2020. Modified Poisson regression was used for the association between active first stage of labour duration and adverse neonatal outcomes. 94.2% experienced a delivery with normal neonatal outcomes. Absolute risk for severe outcomes increased from 1.9 to 3.0%, moderate outcomes increased from 2.8 to 6.2% (> 10.1 h). Compared to the reference, (< 5.1 h; median), the adjusted relative risk (aRR) of severe neonatal outcome significantly increased beyond 10.1 h (> 90th percentile) (aRR 1.53, 95% CI 1.26, 1.87), for moderate neonatal outcome the aRR began to slowly increase beyond 5.1 h (≥ 50 percentile; aRR 1.40, 95% CI 1.24, 1.58). Mediation analysis indicate that most of the association was due to a longer active first stage of labour, 13% (severe neonatal outcomes) and 20% (moderate neonatal outcomes) of the risk was mediated (indirect effect) by longer second stage of labour duration. We report an association between increasing active first stage duration and increased risk of adverse neonatal outcomes. We did not observe a clear labour duration risk threshold.

Latent phase duration and associated outcomes: a contemporary, population-based observational study.

BACKGROUND: Little is known about the latent phase of labor, including whether its duration influences subsequent labor processes or birth outcomes. OBJECTIVE: This study aimed to describe the duration of the latent phase of labor from self-report of the onset of painful contractions to a cervical dilation of 5 cm in a large, Swedish population and evaluate the association between the duration of the latent phase of labor and perinatal processes and outcomes that occurred during the active phase of labor, second stage of labor, birth and immediately after delivery, stratified by parity. STUDY DESIGN: This was a population-based cohort study of 67,267 pregnancies with deliveries between 2008 and 2020 in the Stockholm-Gotland Regions, Sweden. Nulliparous and parous women without a history of cesarean delivery in spontaneous labor with a term (≥37 weeks of gestation), singleton, live, and vertex fetus without major malformations were included. Imputation was used if the notation of the end of the latent phase of labor (ie, cervical dilation of 5 cm) was missing in the partograph. Multivariable logistic regression was used to estimate the association with adjusted odds ratios and 95% confidence intervals, controlling for potential covariates. RESULTS: Including the time from painful contraction onset to a cervical dilation of 5 cm, the median durations of the latent phase of labor were 16.0 (interquartile range, 10.0-26.6) hours for nulliparous women and 9.4 (interquartile range, 5.9-15.3) hours for multiparous women. The durations of the latent phase of labor beyond the median were associated with increased odds of labor dystocia diagnosis during the first stage active phase or second stage of labor and interventions commonly associated with dystocia (amniotomy, oxytocin augmentation, epidural, and cesarean delivery). The duration of the latent phase of labor of ≥90th percentile vs less than the median in nulliparous women demonstrated an increased risk of adverse neonatal outcomes (Apgar score of <7 at 5 minutes and neonatal intensive care unit admission), chorioamnionitis, and fetal occiput posterior. In multiparous women, longer duration of the latent phase of labor was associated with an increased risk of neonatal intensive care unit admission and chorioamnionitis but was not associated with an Apgar score of <7 at 5 minutes. The duration of the latent phase of labor was not associated with additional markers of maternal risk. CONCLUSION: The duration of the latent phase of labor in nulliparous women was longer than that of multiparous women at each point of distribution. A longer duration of the latent phase of labor was associated with more frequent dystocia diagnoses and related interventions during the first stage active phase or second stage of labor, including cesarean delivery, nulliparous fetal occiput posterior position, chorioamnionitis, and markers of neonatal morbidity. More research is needed to identify potential mediating paths between the duration of the latent phase of labor and neonatal morbidity.

How about the evidence assessment tools used in education and management systematic reviews?

Objectives: To systematically analyze the use of evidence assessment tools in systematic reviews of management and education. Study design and setting: We systematically searched selected literature databases and websites to identify systematic reviews on management and education. We extracted general information of the included studies and information about the evidence assessment tool they applied, including whether it was used for methodological quality assessment, reporting quality assessment or evidence grading, as well as the name, reference, publication year, version and original intended use of the tool, the role of the tool in the systematic review, and whether the quality determination criteria were given. Results: A total of 299 systematic reviews were included, of which only 34.8% used evidence assessment tools. A total of 66 different evidence assessment tools were used, of which Risk of Bias (ROB) and its updated version (n = 16, 15.4%) were the most frequent. The specific roles of the evidence assessment tools were reported clearly in 57 reviews, and 27 reviews used two tools. Conclusion: Evidence assessment tools were seldom used in systematic reviews in social sciences. The understanding and reporting of evidence assessment tools among the researchers and users still needs improvement.

Surgery for angiosarcoma and other cardiac sarcomas: A single-institution experience.

Background: Cardiac sarcomas are rare malignancies with a poor prognosis. Although angiosarcoma is the most common histological subtype, its features are poorly characterized. This study aimed to compare the clinical characteristics of the various cardiac sarcomas and the surgical techniques used and to identify factors influencing the prognosis. Methods: Forty patients who underwent surgery for cardiac sarcomas were included; 60% of them had angiosarcoma. Clinical characteristics, tumor location, surgical techniques used, and the prognosis were compared between patients with angiosarcoma and patients with other subtypes. Kaplan-Meier curves and multivariable Cox regression were used to identify predictors of postoperative survival. Results: Angiosarcomas were more likely than the other subtypes to present as pericardial effusion (85% vs 50%, P = .014). Early surgery was performed (median 24.0 days) regardless of histological subtype. The surgical technique varied according to histological subtype. Mean postoperative survival was 10 months. A positive margin (P = .13), high Ki-67 index (P = .19), younger age (P = .86), and angiosarcoma (P = .87) were identified to be potentially poor prognostic factors in univariate analyses. Cox regression identified R0 resection to be the only significant independent predictor of the prognosis after surgery (hazard ratio, 0.423, P = .039). Conclusions: Angiosarcoma differs from other subtypes of cardiac sarcoma in terms of clinical symptoms, tumor location, surgical techniques used, and prognosis. Early surgery is needed regardless of subtype. R0 resection is the only independent predictor of postoperative survival, and complete resection is usually achievable. The prognosis may be poorer in patients with a positive margin, high Ki-67 index, younger age, and angiosarcoma.