Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current ...lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRIIocy−/−), we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility.
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•TGF-β is an osteocyte-intrinsic regulator of perilacunar/canalicular remodeling (PLR)•Osteocytes actively maintain bone quality through regulated control of PLR•Osteocytic PLR is the cellular mechanism by which TGF-β controls bone quality•Defects in PLR cause severe bone fragility, even when bone mass is normal
Resistance to fracture requires healthy bone mass and quality. However, the cellular mechanisms regulating bone quality are unclear. Dole et al. show that osteocyte-intrinsic TGF-β signaling maintains bone quality through perilacunar/canalicular remodeling. Thus, osteocytes mediate perilacunar/canalicular remodeling and osteoclast-directed remodeling to cooperatively maintain bone quality and mass and prevent fragility.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Since Friedman's seminal publication on laboring women, numerous publications have sought to define normal labor progress. However, there is paucity of data on contemporary labor cervicometry ...incorporating both maternal and neonatal outcomes. The objective of this study is to establish intrapartum prediction models of unfavorable labor outcomes using machine-learning algorithms. Consortium on Safe Labor is a large database consisting of pregnancy and labor characteristics from 12 medical centers in the United States. Outcomes, including maternal and neonatal outcomes, were retrospectively collected. We defined primary outcome as the composite of following unfavorable outcomes: cesarean delivery in active labor, postpartum hemorrhage, intra-amniotic infection, shoulder dystocia, neonatal morbidity, and mortality. Clinical and obstetric parameters at admission and during labor progression were used to build machine-learning risk-prediction models based on the gradient boosting algorithm. Of 228,438 delivery episodes, 66,586 were eligible for this study. Mean maternal age was 26.95 ± 6.48 years, mean parity was 0.92 ± 1.23, and mean gestational age was 39.35 ± 1.13 weeks. Unfavorable labor outcome was reported in 14,439 (21.68%) deliveries. Starting at a cervical dilation of 4 cm, the area under receiver operating characteristics curve (AUC) of prediction models increased from 0.75 (95% confidence interval, 0.75-0.75) to 0.89 (95% confidence interval, 0.89-0.90) at a dilation of 10 cm. Baseline labor risk score was above 35% in patients with unfavorable outcomes compared to women with favorable outcomes, whose score was below 25%. Labor risk score is a machine-learning-based score that provides individualized and dynamic alternatives to conventional labor charts. It predicts composite of adverse birth, maternal, and neonatal outcomes as labor progresses. Therefore, it can be deployed in clinical practice to monitor labor progress in real time and support clinical decisions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
We calculate the financial margins for delivery of routine antenatal care as reimbursed by Medicaid. Prenatal care cost varies with overhead, health care provider type, and number of ...office visits. Antenatal care is only one component of the global maternity bundle, which also includes intrapartum and postpartum care.
Methods
Time for provision of low‐risk antenatal care was determined prospectively from a study of 133 low‐risk pregnant patients. Health care provider time cost was estimated using mean wages for obstetricians and midwives. Margins were estimated by subtracting cost of provider services and overhead for the antenatal component of maternity care from total Medicaid reimbursement for the pregnancy global package (CPT 59400) using 2015 dollars. The maternity bundle elements of routine prenatal laboratory tests, ultrasounds, intrapartum care, and postpartum care were not included in our analysis of cost components.
Results
Patients received an average of 215 minutes of direct provider time per pregnancy. At the 50th percentile for physician payment and assuming overhead is 53.4% of revenue, practice margins varied by state from −$1067 to +$675, with a median of −$357. Median margins for midwifery care were +$15, with a range of −$579 to +$885. Margins were negative if overhead costs exceeded 33% of revenue for physician care and 55% of revenue for midwifery care.
Discussion
In many states, Medicaid reimbursement for the global maternity package is less than the actual cost of antenatal care alone. Improving reimbursement or decreasing costs is necessary to make maternity care more cost‐effective.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Novel electrophilic trisubstituted ethylene monomers, alkyl ring-substituted 2-cyano-3-phenyl-2-propenamides, RC
6
H
4
CH=C(CN)CONH
2
(where R is 2-methyl, 3-methyl, 4-methyl, 4-ethyl, 4-
i
-propyl, ...4-
i
-butyl, and 4-
t
-butyl), were synthesized by potassium hydroxide catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and cyanoacetamide, and characterized by CHN elemental analysis, IR,
1
H- and
13
C-NMR. Novel copolymers of the ethylenes and styrene were prepared at equimolar monomer feed composition by solution copolymerization in the presence of a radical initiator, AIBN at 70 °C. The composition of the copolymers was calculated from nitrogen analysis, and the structures were analyzed by IR,
1
H- and
13
C-NMR, GPC, DSC, and TGA. High
T
g
of the copolymers in comparison with that of polystyrene indicates a substantial decrease in chain mobility of the copolymer due to the high dipolar character of the trisubstituted ethylene monomer unit. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200–500 °C range with residue (5–7 wt%), which then decomposed in the 500–800 °C range.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Funding Acknowledgements
Type of funding sources: None.
Background
Atrial fibrillation (AF) is a known risk factor for cognitive impairment and dementia. Recent data suggests that successful ...restoration of sinus rhythm by catheter ablation improves cognitive outcomes. Purpose: Our aim was to perform a systematic review and meta-analysis of the available data regarding the effectiveness of AF catheter ablation on neurocognitive outcomes. Methods: A comprehensive literature search was performed through December 1, 2020, for all eligible studies comparing neurocognitive outcomes in AF patients with or without AF catheter ablation. Clinical outcomes included rate of dementia, cognitive function by Montreal Cognitive Assessment (MOCA) and Mini-Mental State Examination (MMSE) scores. Additional outcomes included the impact of time in sinus rhythm on neurocognitive outcomes. Results: We identified 11 studies which evaluated the effect of AF catheter ablation on dementia rate, MMSE and MOCA score. Meta-analysis of observational results indicates a decreased risk of dementia (risk ratio 0.51; 95% CI: 0.43 to 0.60; p <0.001) and an improvement in MOCA scores (2.92 points, p < 0.001) but not MMSE scores in patients undergoing AF catheter ablation compared to medical therapy. In addition, the maintenance of sinus rhythm was identified as a significant factor in dementia rate and improvement of MMSE and MOCA scores observed post catheter ablation therapy. Conclusion: AF catheter ablation may reduce the incidence of dementia and improve cognitive function. A large-scale randomized control trial is warranted before recommendations can be made regarding AF ablation and cognitive outcomes. Abstract Figure.
IntroductionSince Friedman's seminal publication on laboring women, numerous publications have sought to define normal labor progress. However, there is paucity of data on contemporary labor ...cervicometry incorporating both maternal and neonatal outcomes. The objective of this study is to establish intrapartum prediction models of unfavorable labor outcomes using machine-learning algorithms.Materials and methodsConsortium on Safe Labor is a large database consisting of pregnancy and labor characteristics from 12 medical centers in the United States. Outcomes, including maternal and neonatal outcomes, were retrospectively collected. We defined primary outcome as the composite of following unfavorable outcomes: cesarean delivery in active labor, postpartum hemorrhage, intra-amniotic infection, shoulder dystocia, neonatal morbidity, and mortality. Clinical and obstetric parameters at admission and during labor progression were used to build machine-learning risk-prediction models based on the gradient boosting algorithm.ResultsOf 228,438 delivery episodes, 66,586 were eligible for this study. Mean maternal age was 26.95 ± 6.48 years, mean parity was 0.92 ± 1.23, and mean gestational age was 39.35 ± 1.13 weeks. Unfavorable labor outcome was reported in 14,439 (21.68%) deliveries. Starting at a cervical dilation of 4 cm, the area under receiver operating characteristics curve (AUC) of prediction models increased from 0.75 (95% confidence interval, 0.75-0.75) to 0.89 (95% confidence interval, 0.89-0.90) at a dilation of 10 cm. Baseline labor risk score was above 35% in patients with unfavorable outcomes compared to women with favorable outcomes, whose score was below 25%.ConclusionLabor risk score is a machine-learning-based score that provides individualized and dynamic alternatives to conventional labor charts. It predicts composite of adverse birth, maternal, and neonatal outcomes as labor progresses. Therefore, it can be deployed in clinical practice to monitor labor progress in real time and support clinical decisions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
8.
Uterine Sarcomas: Then and Now SHAH, Shaan H; JAGANNATHAN, Jyothi P; KRAJEWSKI, Katherine ...
American journal of roentgenology (1976),
07/2012, Volume:
199, Issue:
1
Journal Article
Peer reviewed
The purpose of this article is to provide an updated review of uterine sarcomas. The traditionally described neoplasms are reviewed as well as several recently characterized entities in terms of ...their imaging and clinical aspects. We attempt to provide a longitudinal imaging overview, from initial presentation to follow-up. Imaging features are also described of response to traditional therapeutic agents and newer targeted agents.
A greater understanding of the pathogenesis has improved our ability to image and treat uterine sarcomas, both at initial staging and on follow-up. Targeted therapy is assuming an increasingly important role in the management of these lesions. It is imperative for radiologists to be aware of response characteristics and potential complications of these agents as well as conventional chemotherapeutic agents.
The American Cancer Society anticipates the diagnosis of 80,000 new cases of lymphoma in the US in 2013. Cancer Research UK estimates that more than 80% of Hodgkin Lymphoma (HL) patients and more ...than 60% of Non-Hodgkin Lymphoma (NHL) patients will be alive 5 or more years after diagnosis. As survival rates improve, focus shifts to ensuring quality of life in survivors and decreasing potential toxicity. Radiological procedures play a prominent role in diagnosis, staging and assessment of treatment response. Exposure to ionizing radiation has been linked to an increased risk of malignancy (Pearce et al 2012, Miglioretti et al 2013, Mathews et al 2013). Cumulative exposure in excess of 75mSv has been estimated to increase cancer mortality by 7.3% (Cardis et al 2007). There is a paucity of data in the literature regarding cumulative radiation exposure in patients with lymphoma. In cancer treatment, the aim is individualized management strategies. This should also be the goal for diagnostic procedures (O' Neill et al 2011, Fletcher et al 2012).
A retrospective review of all patients on a prospectively maintained database with biopsy proven HL or NHL between January 2009 and July 2012 was conducted in a University hospital group. The cumulative effective radiation dose (CED) was calculated using standardized procedure-specific radiation dose levels.
Four hundred and eighty six patients were included in the study. Mean (SD) age at diagnosis was 59 (17) years and 15% were aged < 40. Fifty-nine percent were men. Sixteen percent had HL; 84% had NHL. There were a total of 1127 patient-years of follow-up, with 15% having <1 year and 10% having 5 or more years of follow-up.
Ninety-nine per cent of patients had diagnostic imaging. A total of 5748 radiological procedures were performed, equivalent to one procedure every 70 patient days of follow-up.
The median estimated total CED ( IQR) per subject was 69mSv (42-118). Forty- six percent had a total CED >75mSv and 14% had a total CED >150mSv – SeeFigure 1. CT contributed 89% of the radiation dose and PET-CT contributed 8%.
Patients aged <40 had a median CED (IQR) of 89mSv (55-124). Seventy-five per cent of these patients had a potentially curable malignancy (66% had HL; 5% had Diffuse Large B Cell Lymphoma; 4% had Burkitt Lymphoma). Patients who underwent stem cell transplantation had a median CED (IQR) of 162mSv (135-225) with 59% having radiotherapy as part of their management.
Univariate analysis showed that age (p<0.001), duration of lymphoma (p<0.001) and stage (<0.001) were associated with CED.
This study highlights the considerable ionizing radiation exposure from diagnostic imaging in patients with lymphoma. This is especially relevant in young people who would be considered the most radiosensitive and at highest risk for secondary malignancies.
Low grade lymphomas are relapsing and remitting in nature and frequently require re-staging imaging over many years. Longer follow-up will be required here to potentially explain the non-significant trend between histological subtype and different CED.
The American College of Radiology stated in 2013 that when used appropriately, the benefits of ionizing radiation far outweigh the risks. However, to minimize risk, institutions should participate in national dose registries. With the widespread use of Picture Archiving and Communication System (PACS), this will be feasible.
Low dose CT imaging has emerged as a mechanism for minimizing CED. Dose reduction strategies incorporating patient-specific information would optimize imaging while minimizing the harmful effects (Shah et al 2012). Novel CT reconstruction algorithms allow diagnostic quality imaging to be obtained at reduced radiation doses without the prohibitive noise that would otherwise be present (Prakash et al 2010).
Procedures which do not involve ionizing radiation such as MRI and ultrasound are becoming increasingly popular. There is growing interest in PET-MRI for staging of malignancies (Appenzeller 2013) but as yet, PET-CT remains superior.
For patients with potentially curable lymphoma, particularly young patients with higher CED, consideration should be given to these strategies.
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No relevant conflicts of interest to declare.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Uncontrolled proliferation is a hallmark of cancer. In breast cancer, immunohistochemical assessment of the proportion of cells staining for the nuclear antigen Ki67 has become the most widely used ...method for comparing proliferation between tumor samples. Potential uses include prognosis, prediction of relative responsiveness or resistance to chemotherapy or endocrine therapy, estimation of residual risk in patients on standard therapy and as a dynamic biomarker of treatment efficacy in samples taken before, during, and after neoadjuvant therapy, particularly neoadjuvant endocrine therapy. Increasingly, Ki67 is measured in these scenarios for clinical research, including as a primary efficacy endpoint for clinical trials, and sometimes for clinical management. At present, the enormous variation in analytical practice markedly limits the value of Ki67 in each of these contexts. On March 12, 2010, an international panel of investigators with substantial expertise in the assessment of Ki67 and in the development of biomarker guidelines was convened in London by the cochairs of the Breast International Group and North American Breast Cancer Group Biomarker Working Party to consider evidence for potential applications. Comprehensive recommendations on preanalytical and analytical assessment, and interpretation and scoring of Ki67 were formulated based on current evidence. These recommendations are geared toward achieving a harmonized methodology, create greater between-laboratory and between-study comparability, and allow earlier valid applications of this marker in clinical practice.
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