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Calcium ions are essential to signal transduction in virtually all cells, where they coordinate processes ranging from embryogenesis to neural function. Although optical probes for intracellular calcium imaging have been available for decades, the development of probes for noninvasive detection of intracellular calcium signaling in deep tissue and intact organisms remains a challenge. To address this problem, we synthesized a manganese-based paramagnetic contrast agent, ManICS1-AM, designed to permeate cells, undergo esterase cleavage, and allow intracellular calcium levels to be monitored by magnetic resonance imaging (MRI). Cells loaded with ManICS1-AM show changes in MRI contrast when stimulated with pharmacological agents or optogenetic tools; responses directly parallel the signals obtained using fluorescent calcium indicators. Introduction of ManICS1-AM into rodent brains furthermore permits MRI-based measurement of neural activation in optically inaccessible brain regions. These results thus validate ManICS1-AM as a calcium sensor compatible with the extensive penetration depth and field of view afforded by MRI. There are only few MRI-compatible calcium reporters and they are limited to measuring extracellular calcium levels. Here the authors develop and validate a cell-permeable, manganese-based paramagnetic MRI contrast agent that enables monitoring intracellular calcium signals in vivo in the rat brain.

BackgroundWith a large body of literature demonstrating positive volume-outcome relationships for most major operations, minimum volume requirements have been suggested for concentration of cases to high-volume centers (HVCs). However, data are limited regarding disparities in access to these hospitals for pancreatectomy patients.MethodsThe 2005–2018 National Inpatient Sample (NIS) was queried for all elective adult hospitalizations for pancreatectomy. Hospitals performing more than 20 annual cases were classified as HVCs. Mixed-multivariable regression models were developed to characterize the impact of demographic factors and case volume on outcomes of interest.ResultsOf an estimated 127,527 hospitalizations, 79.8% occurred at HVCs. Patients at these centers were more frequently white (79.0 vs 70.8%; p < 0.001), privately insured (39.4 vs 34.2%; p < 0.001), and within the highest income quartile (30.5 vs 25.0%; p < 0.001). Adjusted analysis showed that operations performed at HVCs were associated with reduced odds of in-hospital mortality (adjusted odds ratio [AOR], 0.43; 95% confidence interval [CI], 0.34–0.55), increased odds of discharge to home (AOR, 1.17; 95% CI, 1.04–1.30), shorter hospital stay (β, −0.81 days; 95% CI, −1.2 to −0.40 days), but similar costs. Patients who were female (AOR, 0.88; 95% CI, 0.79–0.98), non-white (black: AOR, 0.66; 95% CI, 0.59–0.75; Hispanic: AOR, 0.56; 95% CI, 0.47–0.66; reference, white), insured by Medicaid (AOR, 0.63; 95% CI, 0.56–0.72; reference, private), and within the lowest income quartile (AOR, 0.73; 95% CI, 0.59–0.90; reference, highest) had decreased odds of treatment at an HVC.ConclusionsFor those undergoing pancreatectomies, HVCs realize superior clinical outcomes but treat lower proportions of female, non-white, and Medicaid populations. These findings may have implications for improving access to high-quality centers.

A body of literature has previously highlighted the impact of health insurance on observed disparities in congenital cardiac operations. With aims of improving access to healthcare for all patients, the Affordable Care Act (ACA) expanded Medicaid coverage to nearly all eligible children in 2010. Therefore, the present population-based study aimed to examine the association of Medicaid coverage with clinical and financial outcomes in the era the ACA. Records for pediatric patients (≤ 18 years) who underwent congenital cardiac operations were abstracted from the 2010–2018 Nationwide Readmissions Database. Operations were stratified using the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Category. Multivariable regression models were developed to evaluate the association of insurance status on index mortality, 30-day readmissions, care fragmentation, and cumulative costs. Of an estimated 132,745 hospitalizations for congenital cardiac surgery from 2010 to 2018, 74,925 (56.4%) were insured by Medicaid. The proportion of Medicaid patients increased from 57.6 to 60.8% during the study period. On adjusted analysis, patients with Medicaid insurance were at an increased odds of mortality (1.35, 95%CI: 1.13–1.60) and 30-day unplanned readmission (1.12, 95%CI: 1.01–1.25), experienced longer lengths of stay (+ 6.5 days, 95%CI 3.7–9.3), and exhibited higher cumulative hospitalization costs (+ $21,600, 95%CI: $11,500–31,700). The total hospitalization cost-burden for patients with Medicaid and private insurance were $12.6 billion and $8.06 billion, respectively. Medicaid patients exhibited increased mortality, readmissions, care fragmentation, and costs compared to those with private insurance. Our results of outcome variation by insurance status indicate the necessity of policy changes to attempt to approach equality in surgical out comes for this high-risk cohort. Graphical Abstract Baseline characteristics, trends, and outcomes by insurance status over the ACA rollout period 2010–2018

[...]some causes of preterm birth have implications for women’s lifelong health; gestational conditions that lead to preterm birth are independent risk factors for maternal illness such as diabetes, cardiovascular conditions, and premature mortality [11]. Future developments to better understand preterm birth include enhanced research into underlying genetic risks and pathological mechanisms, identification of at-risk populations, investigating the impact of adverse societal and economic influences including climate change and structural racism, and evaluation of targeted interventions. Implementing interventions late in pregnancy, such as progesterone and cerclage, may only make a very small reduction to the preterm birth rate at a population level, whereas earlier interventions, such as improving family planning, preconception health, and HPV vaccination to avoid CIN treatment, may have more widespread impact. Without an attempt to classify preterm births at a more granular level, we risk obstructing the identification of interventions, research studies, and policies that have the potential to improve outcomes for women and babies.

Background Nausea and vomiting of pregnancy (NVP) affects up to 90% of pregnant women but many struggle to access guideline-recommended care. Following a King’s Policy Institute policy laboratory, arranged to explore barriers to care, it was recommended that a scoping review of current national practice was carried out. This study aims to describe NVP services in England, Scotland and Wales and compare management to national guidance. Methods An online survey was distributed to all 139 maternity units in England, Scotland and Wales using freedom of information services. Data were downloaded onto an Excel spreadsheet and statistical analysis performed using GraphPad Prism 10. Results Responses were received from 129/139 hospitals giving a response rate of 92.8%. Routine screening for NVP/HG at a woman’s booking visit is offered in 37/129 (28.7%) of the hospitals. Treatment in the community was offered in 19/129 (14.8%) and ambulatory management available in 108/129 (83.7%) of hospitals that responded. As per RCOG guidance only 60/129 (47%) of hospitals correctly prescribe a combination of recommended first, second and third-line antiemetics and whether the maternity unit is secondary or tertiary, or whether patients are primarily managed in an obstetric or gynaecology setting, does not influence provision of guideline-recommended care, (secondary 39/85 (45.8%) vs. tertiary 21/44 (47.7%) p  = 0.84 and obstetric 12/34 (35.3%) vs. gynaecology setting 48/95 (50.5%) p  = 0.13, respectively). A proton pump inhibitor was prescribed in 64/129 (49.6%) of units and thiamine for patients with persistent vomiting in 90/129 (69.8%). Guideline-recommend intravenous fluid management (0.9% normal saline) is used in 93/129 (72.1%) of units. In those where it is not, 5/36 (13.9%) use dextrose solution (recognised to precipitate Wernicke’s encephalopathy). Routine mental health screening occurs in 54/129 (41.9%) of units. Pre-pregnancy counselling is offered to women with a history of severe NVP/HG planning a future pregnancy in 22/129 (17.1%) of units. Conclusions Significant variation in HG care exists across England, Scotland and Wales. Despite guidance published by the RCOG the treatment women currently receive is not routinely evidence-based and in some cases has potential to cause harm.

This study used a national cohort to characterize the impact of inter-hospital transfer status on outcomes following nonelective cholecystectomy for cholecystitis. Nonelective cholecystectomies were identified using the 2016–2019 National Inpatient Sample. Multivariable models adjusting for patient and hospital characteristics were utilized to assess outcomes of interest. Of an estimated 530,696 patients, 5.3% were transferred. Transferred patients were older, more often male, and more likely to report income in the 0th-25th percentile, compared to others. After adjustment, transfer was associated with increased odds of infectious complications (AOR 1.31, 95%CI 1.06–1.60) and non-home discharge (AOR 1.59, 95%CI 1.45–1.74), but not mortality. Transfer was linked to a $600 cost decrement at the operating hospital (95%CI -$880-330). Transfer status is associated with greater postoperative infection, but not mortality. Given that disparities may play a role in transfer decisions, more work must be done to identify transfer drivers and improve patient outcomes. •Transfer is associated with greater odds of postoperative infectious complications.•Transfer is not associated with differences in in-hospital mortality.•Lower income and greater comorbidity burden are linked with higher odds of transfer.•Medicare coverage is associated with greater transfer odds, relative to private pay.•Further studies can identify other transfer drivers to optimize patient outcomes.

ObjectiveTo assess the impact of congenital heart disease (CHD) on resource utilisation and clinical outcomes in patients undergoing major elective non-cardiac operations.BackgroundDue to advances in congenital cardiac management in recent years, more patients with CHD are living into adulthood and are requiring non-cardiac operations.MethodsThe 2010–2018 Nationwide Readmissions Database was used to identify all adults undergoing major elective operations (pneumonectomy, hepatectomy, hip replacement, pancreatectomy, abdominal aortic aneurysm repair, colectomy, gastrectomy and oesophagectomy). Multivariable regression models were used to categorise key clinical outcomes.ResultsOf an estimated 4 941 203 adults meeting inclusion criteria, 5234 (0.11%) had a previous diagnosis of CHD. Over the study period, the incidence of CHD increased from 0.06% to 0.17%, p<0.001. CHD patients were on average younger (63.3±14.8 vs 64.4±12.5 years, p=0.004), had a higher Elixhauser Comorbidity Index (3.3±2.2 vs 2.3±1.8, p<0.001) and received operations at high volume centres more frequently (66.6% vs 62.0%, p=0.003). Following risk adjustment, these patients had increased risk of in-hospital mortality (adjusted risk ratio (ARR): 1.76, 95% CI 1.25 to 2.47), experienced longer hospitalisation durations (+1.6 days, 95% CI 1.3 to 2.0) and cost more (+$8370, 95% CI $6686 to $10 055). Furthermore, they were more at risk for in-hospital complications (ARR: 1.24 95% CI 1.17 to 1.31) and endured higher adjusted risk of readmission at 30 days (ARR: 1.32 95% CI 1.13 to 1.54).ConclusionsAdults with CHD are more frequently comprising the major elective operative cohort for non-cardiac cases. Due to the inferior clinical and financial outcomes suffered by this population, perioperative risk stratification may benefit from the inclusion of CHD as a factor that portends unfavourable outcomes.

Necrotizing enterocolitis (NEC) is a devastating illness with mortality rates approaching 26 ​%, with 4 ​% of patients with congenital heart disease (CHD) receiving this diagnosis. In this retrospective cohort study, the Pediatric Health Information System database was used to compare outcomes among patients with NEC diagnoses between 2019 and 2021 by CHD. The association of clinical factors with the outcomes of interest were compared using multivariable logistic regression. Of 2415 pediatric patients diagnosed with NEC, 955 (39.5 ​%) had a diagnosis of CHD. Those with CHD were more frequently White and born at a later gestational age. Antibiotic courses were similar; however, CHD patients had lower rates of post-antibiotic operations (18.0 ​% vs 32.1 ​%, p ​< ​0.001) and in-hospital mortality (11.1 ​% vs 15.5 ​%, p ​= ​0.001). On adjusted analysis, patients without CHD were twice as likely to undergo an abdominal operation. Compared with patients without CHD, those with CHD had decreased rates of antibiotic failure for NEC diagnosis despite similar treatment courses. Distinct outcomes of bowel ischemia among infants with CHD warrant further study of treatment strategies that may differ from those of classical NEC. Retrospective Cohort Study. III. •Necrotizing enterocolitis (NEC) is a devastating illness with mortality rates approaching 26 ​%, yet 4 ​% of patients with congenital heart disease (CHD) receive a diagnosis of NEC.•In this retrospective cohort study, we found that those with CHD had decreased rates of antibiotic failure for NEC diagnosis despite similar treatment courses.•Distinct outcomes of bowel ischemia among infants with CHD warrant study of treatment strategies that may differ from those of classical NEC.

Background Retained surgical foreign bodies (RFB) are associated with inferior clinical and financial outcomes. The present work examined a nationally representative sample of all major operations to identify factors associated with RFB. Study Design The 2005-2017 National Inpatient Sample was used to identify adults undergoing cardiac, neurosurgical, orthopedic, genitourinary, gastrointestinal, vascular, and thoracic operations. International Classifications of Diseases 9th-10th Revisions diagnosis codes were used to identify instances of RFB. Results Of an estimated 71,445,042 hospitalizations, .02% had a diagnosis of RFB, with decreasing incidence from .03 to .02% over the study period (NPtrend < .001). Relative to vascular operations, gastrointestinal (adjusted odds ratio [AOR] 2.12), thoracic (AOR 1.80), and multi-cavity (AOR 2.17) were associated with greater odds of RFB. Laparoscopic approach (AOR .33) and trauma-associated admission (AOR .52, all P < .001) were associated with reduced odds of RFB. Despite similar mortality, RFB was associated with increased odds of pulmonary infection (AOR 1.62), sepsis (AOR 1.26), and wound infection (AOR 5.15), as well as a 2.3-day increment in length of stay and $7700 in hospitalization costs (all P < .001). Conclusion The development of novel mitigation strategies may reduce the incidence of RFB in high-risk populations, such as those undergoing gastrointestinal, thoracic, and multi-cavity operations.

Racial disparities in extracorporeal membrane oxygenation (ECMO) outcomes in patients with a broad set of indications are not well documented. Adults requiring ECMO were identified in the 2016–2019 National Inpatient Sample. Patient and hospital characteristics, including mortality, clinical outcomes, and resource utilization were analyzed using multivariable regressions. Of 43,190 adult ECMO patients, 67.8% were classified as White, 18.1% Black, and 10.4% Hispanic. Although mortality for Whites declined from 47.5 to 41.0% (P = 0.002), it remained steady for others. Compared to White, Asian/Pacific Islander (PI) race was linked to increased odds of mortalty (AOR = 1.4, 95% CI = 1.1–2.0). Black race was associated with increased odds of acute kidney injury (AOR = 1.4, 95%-CI: 1.2–1.7), while Hispanic race was linked to neurologic complications (AOR 21.6; 95% CI 1.2–2.3). Black and Hispanic race were also associated with increased incremental costs. Race-based disparities in ECMO outcomes persist in the United States. Further work should aim to understand and mitigate the underlying reasons for such findings. •Characteristics differed by race among patients treated with extracorporeal support.•Mortality for White patients decreased significantly.•Mortality for Black and Asian patients remained stable.•Non-White race was linked to increased complications and resource utilization.•Rates of non-home discharge were comparable across race.