Search

Pain is a multidimensional construct. The purpose of this cross-sectional, single-centre study was to evaluate the relationship between postpartum pain type with pain intensity and opioid use in people with and without opioid use disorder (OUD).Postpartum pain type was coded from McGill Pain Questionnaire and Patient-Reported Outcome Measurement Information System (PROMIS) inventories in people with or without OUD after childbirth in a 4-month period. The co-primary outcomes were pain intensity (0-10 scale) and total inpatient oxycodone (mg). Multivariable linear mixed-effects models assessed between- and within-person relationships for pain type (primary predictor) and outcomes.There were 44 522 unique pain scores and types from 2610 people. Pain types were associated with pain intensity (P0.001). Between-person comparisons showed affective pain was associated with a small but higher total oxycodone dose (difference 1.04 mg compared with no affective pain, P0.001). Among people with OUD, within-person comparisons showed that the presence of affective pain resulted in pain scores 1 point higher than when affective pain was not present (P=0.002); between-person comparisons showed that people with affective pain had pain scores 6 points higher (P=0.048). Within-person and between-person comparisons among OUD showed that nociceptive/neuropathic pain was associated with a higher total oxycodone dose (1.6 and 11.4 mg, respectively).Postpartum pain type was associated with pain intensity and opioid use. Further research is required to address the multiple dimensions of postpartum pain in people with and without OUD to improve treatment of postpartum pain.

More than twenty years ago, the Accreditation Council for Graduate Medical Education and the American Board of Medical Specialties began the conversion of graduate medical education from a structure- and process-based model to a competency-based framework. The educational outcomes assessment tool, known as the Milestones, was introduced in 2013 for seven specialties and by 2015 for the remaining specialties, including pediatric surgery. Designed to be an iterative process with improvements over time based on feedback and evidence-based literature, the Milestones started the evolution from 1.0 to 2.0 in 2016. The formation of Pediatric Surgery Milestones 2.0 began in 2019 and was finalized in 2021 for implementation in the 2022-2023 academic year. Milestones 2.0 are fewer in number and are stated in more straightforward language. It incorporated the harmonized milestones, subcompetencies for non-patient care and non-medical knowledge that are consistent across all medical and surgical specialties. There is a new Supplemental Guide that lists examples, references and links to other assessment tools and resources for each subcompetency. Milestones 2.0 represents a continuous process of feedback, literature review and revision with goals of improving patient care and maintaining public trust in graduate medical education's ability to self-regulate. LEVEL OF EVIDENCE: V.

Peri-intubation oxygen administration to the pregnant patient during induction of general anaesthesia is critical to avoiding hypoxaemia and harm to the mother and fetus. Recent modelling comparing low-flow with high-flow nasal oxygen in simulated term pregnant women of varying body habitus, taken together with previous work, suggests that face mask preoxygenation with the use of low-flow or high-flow nasal oxygen during the period of apnoea prolongs the safe apnoea period, with the benefit varying by body habitus. Low-flow compared with high-flow nasal oxygen may be easier to combine with face mask preoxygenation and is readily available in all operating theatres, although future improvements in high-flow nasal oxygen delivery systems may improve ease of use for this indication.

Reproductive health is an active area of practice and research for anaesthetists, intensivists, and pain medicine specialists. The purpose of the British Journal of Anaesthesia is to promote the health, welfare, and safety of all persons by disseminating knowledge to further our understanding of anaesthetic principles and improve practice and skills. This includes supporting safe abortion care as an integral part of safe reproductive health.

Purpose:The immunosuppressive tumor microenvironment present in the majority of diffuse glioma limits therapeutic response to immunotherapy. As the determinants of the glioma-associated immune response are relatively poorly understood, the study of glioma with more robust tumor-associated immune responses may be particularly useful to identify novel immunomodulatory factors that can promote T-cell effector function in glioma.Experimental Design:We used multiplex immune-profiling, proteomic profiling, and gene expression analysis to define the tumor-associated immune response in two molecular subtypes of glioma and identify factors that may modulate this response. We then used patient-derived glioma cultures and an immunocompetent murine model for malignant glioma to analyze the ability of tumor-intrinsic factors to promote a CD8+ T-cell response.Results:As compared with isocitrate dehydrogenase (IDH)-mutant astrocytoma, MAPK-activated pleomorphic xanthoastrocytoma (PXA) harbored increased numbers of activated cytotoxic CD8+ T cells and Iba1+ microglia/macrophages, increased MHC class I expression, enrichment of genes associated with antigen presentation and processing, and increased tumor cell secretion of the chemokine CXCL14. CXCL14 promoted activated CD8+ T-cell chemotaxis in vitro, recruited tumor-infiltrating CD8+ T cells in vivo, and prolonged overall survival in a cytotoxic T-cell–dependent manner. The immunomodulatory molecule B7-H3 was also highly expressed in PXA.Conclusions:We identify the MAPK-activated lower grade astrocytoma PXA as having an immune-rich tumor microenvironment and suggest this tumor may be particularly vulnerable to immunotherapeutic modulation. We also identify CXCL14 as an important determinant of the glioma-associated immune microenvironment, sufficient to promote an antitumor CD8+ T-cell response.

Supplementary Figure from CXCL14 Promotes a Robust Brain Tumor-Associated Immune Response in Glioma

Supplementary Data from CXCL14 Promotes a Robust Brain Tumor-Associated Immune Response in Glioma

Purpose: The immunosuppressive tumor microenvironment present in the majority of diffuse glioma limits therapeutic response to immunotherapy. As the determinants of the glioma-associated immune response are relatively poorly understood, the study of glioma with more robust tumor-associated immune responses may be particularly useful to identify novel immunomodulatory factors that can promote T-cell effector function in glioma. Experimental Design: We used multiplex immune-profiling, proteomic profiling, and gene expression analysis to define the tumor-associated immune response in two molecular subtypes of glioma and identify factors that may modulate this response. We then used patient-derived glioma cultures and an immunocompetent murine model for malignant glioma to analyze the ability of tumor-intrinsic factors to promote a CD8+ T-cell response. Results: As compared with isocitrate dehydrogenase (IDH)-mutant astrocytoma, MAPK-activated pleomorphic xanthoastrocytoma (PXA) harbored increased numbers of activated cytotoxic CD8+ T cells and Iba1+ microglia/macrophages, increased MHC class I expression, enrichment of genes associated with antigen presentation and processing, and increased tumor cell secretion of the chemokine CXCL14. CXCL14 promoted activated CD8+ T-cell chemotaxis in vitro, recruited tumor-infiltrating CD8+ T cells in vivo, and prolonged overall survival in a cytotoxic T-cell–dependent manner. The immunomodulatory molecule B7-H3 was also highly expressed in PXA. Conclusions: We identify the MAPK-activated lower grade astrocytoma PXA as having an immune-rich tumor microenvironment and suggest this tumor may be particularly vulnerable to immunotherapeutic modulation. We also identify CXCL14 as an important determinant of the glioma-associated immune microenvironment, sufficient to promote an antitumor CD8+ T-cell response.

The Affordable Care Act has been associated with increased Medicaid coverage for childbirth among low-income US women. We hypothesized that Medicaid expansion was associated with increased use of labor neuraxial analgesia.We performed a cross-sectional analysis of US women with singleton live births who underwent vaginal delivery or intrapartum cesarean delivery between 2009 and 2017. Data were sourced from births in 26 US states that used the 2003 Revised US Birth Certificate. Difference-in-difference linear probability models were used to compare changes in the prevalence of neuraxial labor analgesia in 15 expansion and 11 nonexpansion states before and after Medicaid expansion. Models were adjusted for potential maternal and obstetric confounders with standard errors clustered at the state level.The study sample included 5,703,371 births from 15 expansion states and 5,582,689 births from 11 nonexpansion states. In the preexpansion period, the overall rate of neuraxial analgesia in expansion and nonexpansion states was 73.2% vs 76.3%. Compared with the preexpansion period, the rate of neuraxial analgesia increased in the postexpansion period by 1.7% in expansion states (95% CI, 1.6-1.8) and 0.9% (95% CI, 0.9-1.0) in nonexpansion states. The adjusted difference-in-difference estimate comparing expansion and nonexpansion states was 0.47% points (95% CI, -0.63 to 1.57; P = .39).Medicaid expansion was not associated with an increase in the rate of neuraxial labor analgesia in expansion states compared to the change in nonexpansion states over the same time period. Increasing Medicaid eligibility alone may be insufficient to increase the rate of neuraxial labor analgesia.

Purpose To conduct a systematic review to evaluate the clinical parameters for periodontal diseases in individuals with cleft lip and/or palate (CL/P). Methods The authors searched six indexed databases without language restriction through July 2021. The eligibility criteria were observational studies that compared the periodontal clinical measures of individuals with CL/P to those without CL/P. Meta-analysis was conducted using random-effects models with inverse variance weighting. Results The literature search generated 1277 records, and 40 full-text articles were reviewed. Twenty-three studies comprising 3,235 individuals from 4 continents fulfilled our selection criteria. The meta-analysis revealed significant difference in mean plaque index scores (MD = 0.31, 95%CI = 0.22, 0.41), gingival index scores (MD = 0.50, 95%CI = 0.24, 0.77) and periodontal pocket depth (MD = 0.64, 95%CI = 0.12, 1.16) between individuals with and without CL/P. A slight increase in clinical attachment loss was detected among individuals with CL/P; however, such an increase may have little clinical significance. Conclusions As age is positively related to periodontal disease progression, and individuals with CL/P are more likely to present with more plaque accumulation and gingival inflammation, clinicians should reinforce preventive dental care from an early age.

Tissue engineering involves the seeding of cells into a structural scaffolding to regenerate the architecture of damaged or diseased tissue. To effectively design a scaffold, an understanding of how cells collectively sense and react to the geometry of their local environment is needed. Advances in the development of melt electro-writing have allowed micron and submicron polymeric fibres to be accurately printed into porous, complex and three-dimensional structures. By using melt electrowriting, we created a geometrically relevant in vitro scaffold model to study cellular spatial-temporal kinetics. These scaffolds were paired with custom computer vision algorithms to investigate cell nuclei, cell membrane actin and scaffold fibres over different pore sizes (200–600 µm) and time points (28 days). We find that cells proliferated much faster in the smaller (200 µm) pores which halved the time until confluence versus larger (500 and 600 µm) pores. Our analysis of stained actin fibres revealed that cells were highly aligned to the fibres and the leading edge of the pore filling front, and we found that cells behind the leading edge were not aligned in any particular direction. This study provides a systematic understanding of cellular spatial temporal kinetics within a 3D in vitro model to inform the design of more effective synthetic tissue engineering scaffolds for tissue regeneration. Statement of significance Advances in the development of melt electro-writing have allowed micron and submicron polymeric fibres to be accurately printed into porous, complex and three-dimensional structures. By using melt electrowriting, we created a geometrically relevant in vitro model to study cellular spatial-temporal kinetics to provide a systematic understanding of cellular spatial temporal kinetics within a 3D in vitro model. The insights presented in this work help to inform the design of more effective synthetic tissue engineering scaffolds by reducing cell culture time; which is valuable information for the implant or lab-grown-meat industries.

Managing newborns with kidney failure is a complex undertaking; even under ideal circumstances, dialysis is technically challenging and available therapies are designed for adults. These issues are exacerbated in smaller newborns, and intervention has traditionally not been offered in those below a certain weight threshold. Ethical concerns abound and patients deemed too small for dialysis are typically transitioned to comfort or palliative care. However, many of these neonates are otherwise healthy and would be considered survivable if kidney replacement therapy were available. To challenge the existing paradigm, we present 7 preterm, low birth weight neonates with end-stage kidney disease who were successfully managed using an innovative approach to kidney replacement therapy. These newborns had a median gestational age of 32 weeks (interquartile range [IQR], 32-35) and a median birth weight of 1.58 kg (IQR, 1.41-2.01). Kidney replacement therapy was initiated at a median age of 16 days (IQR, 1.5-40) and a weight of 1.85 kg (IQR, 1.57-2.1). Five of the 7 newborns (71%) survived to hospital discharge. Kidney replacement therapy was provided using 3F and 4F single lumen catheters and a modified ultrafiltration device. Patients experienced excellent metabolic control, and fluid homeostasis was achieved in the first week of life. Furthermore, survivors experienced physiologic weight gain and linear growth throughout their hospitalization. These findings, although preliminary, are encouraging for our smallest patients with kidney failure and suggest that survivability thresholds should be reexamined. At a minimum, neonatologists should be aware that novel approaches exist and may be considered for these challenging patients.

Objective To analyze racial and ethnic disparities in failure to rescue (ie, death) associated with severe maternal morbidity and describe temporal trends. Methods This was a retrospective cohort study using administrative data. Data for delivery hospitalizations with severe maternal morbidity, as defined by the Centers for Disease Control and Prevention, were abstracted from the 1999-2017 National Inpatient Sample. Race and ethnicity were categorized into non-Hispanic White (reference), non-Hispanic Black, Hispanic, other, and missing. The outcome was failure to rescue from severe maternal morbidity. Disparities were assessed using the failure-to-rescue rate ratio (ratio of the failure-to-rescue rate in the racial and minority group to the failure-to-rescue rate in White women), adjusted for patient and hospital characteristics. Temporal trends in severe maternal morbidity and failure to rescue were assessed. Results During the study period, 73,934,559 delivery hospitalizations were identified, including 993,864 with severe maternal morbidity (13.4/1,000; 95% CI 13.3-13.5). Among women with severe maternal morbidity, 4,328 died (4.3/1,000; 95% CI 4.2-4.5). The adjusted failure-to-rescue rate ratio was 1.79 (95% CI 1.77-1.81) for Black women, 1.39 (95% CI 1.37-1.41) for women of other race and ethnicity, 1.43 (95% CI 1.42-1.45) for women with missing race and ethnicity data, and 1.08 (95% CI 1.06-1.09) for Hispanic women. During the study period, the severe maternal morbidity rate increased significantly in each of the five racial and ethnic groups but started declining in 2012. Meanwhile, the failure-to-rescue rate decreased significantly during the entire study period. Conclusion Despite improvement over time, failure to rescue from severe maternal morbidity remains a major contributing factor to excess maternal mortality in racial and ethnic minority women.

Daily evaluations of certified registered nurse anesthetists’ (CRNAs’) work habits by anesthesiologists should be adjusted for rater leniency. The current study tested the hypothesis that there is a pairwise association by rater between leniencies of evaluations of CRNAs’ daily work habits and of didactic lectures. The historical cohorts were anesthesiologists’ evaluations over 53 months of CRNAs’ daily work habits and 65 months of didactic lectures by visiting professors and faculty. The binary endpoints were the Likert scale scores for all 6 and 10 items, respectively, equaling the maximums of 5 for all items, or not. Mixed effects logistic regression estimated the odds of each ratee performing above or below average adjusted for rater leniency. Bivariate errors in variables least squares linear regression estimated the association between the leniency of the anesthesiologists’ evaluations of work habits and didactic lectures. There were 29/107 (27%) raters who were more severe in their evaluations of CRNAs’ work habits than other anesthesiologists (two-sided P

The programmed intermittent epidural bolus technique has shown superiority to continuous epidural infusion techniques, with or without patient-controlled epidural analgesia for pain relief, reduced motor block and patient satisfaction. Many institutions still use patient-controlled epidural analgesia without a background infusion, and a comparative study between programmed intermittent epidural bolus and patient-controlled epidural analgesia without a background infusion has not yet been performed. We performed a randomised, two-centre, double-blind, controlled trial of these two techniques. The primary outcome was the incidence of breakthrough pain requiring a top-up dose by an anaesthetist. Secondary outcomes included: motor block; pain scores; patient satisfaction; local anaesthetic consumption; and obstetric and neonatal outcomes. We recruited 130 nulliparous women who received initial spinal analgesia, and then epidural analgesia was initiated and maintained with either programmed intermittent epidural bolus or patient-controlled epidural analgesia using ropivacaine 0.12% with sufentanil 0.75 µg·ml-1 . The programmed intermittent epidural bolus group had a programmed bolus of 10 ml every hour, with on-demand patient-controlled epidural analgesia boluses of 5 ml with a 20 min lockout, and the patient-controlled epidural analgesia group had a 5 ml bolus with a 12 min lockout interval; the potential maximum volume per hour was the same in both groups. The patients in the programmed intermittent epidural bolus group had less frequent breakthrough pain compared with the patient-controlled epidural analgesia group, 7 (10.9%) vs. 38 (62.3%; p < 0.0001), respectively. There was a significant difference in motor block (modified Bromage score ≤ 4) frequency between groups, programmed intermittent epidural bolus group 1 (1.6%) vs. patient-controlled epidural analgesia group 8 (13.1%); p = 0.015. The programmed intermittent epidural bolus group had greater local anaesthetic consumption with fewer patient-controlled epidural analgesia boluses. Patient satisfaction scores and obstetric or neonatal outcomes were not different between groups. In conclusion, we found that a programmed intermittent epidural bolus technique using 10 ml programmed boluses and 5 ml patient-controlled epidural analgesia boluses was superior to a patient-controlled epidural analgesia technique using 5 ml boluses and no background infusion.

Background Prophylactic epidural morphine administration after unintentional dural puncture with a large-bore needle has been shown to decrease the incidence of post–dural puncture headache. The authors hypothesized that prophylactic administration of intrathecal morphine would decrease the incidence of post–dural puncture headache and/or need for epidural blood patch after unintentional dural puncture. Methods Parturients with an intrathecal catheter in situ after unintentional dural puncture with a 17-g Tuohy needle during intended epidural catheter placement for labor analgesia were enrolled in this randomized, double-blind trial. After delivery, subjects were randomized to receive intrathecal morphine 150 µg or normal saline. The primary outcome was the incidence of post–dural puncture headache. Secondary outcomes included onset, duration, and severity of post–dural puncture headache, the presence of cranial nerve symptoms and the type of treatment the patient received. Results Sixty-one women were included in the study. The incidence of post–dural puncture headache was 21 of 27 (78%) in the intrathecal morphine group and 27 of 34 (79%) in the intrathecal saline group (difference, −1%; 95% CI, −25% to 24%). There were no differences between groups in the onset, duration, or severity of headache, or presence of cranial nerve symptoms. Epidural blood patch was administered to 10 of 27 (37%) of subjects in the intrathecal morphine and 11 of 21 (52%) of the intrathecal saline group (difference 15%; 95% CI, −18% to 48%). Conclusions The present findings suggest that a single prophylactic intrathecal morphine dose of 150 µg administered shortly after delivery does not decrease the incidence or severity of post–dural puncture headache after unintentional dural puncture. This study does not support the clinical usefulness of prophylactic intrathecal morphine after an unintentional dural puncture. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

International Society for Peritoneal Dialysis. Baxter Health Care. Fresenius Medical Care, Germany. Ipsen. Medical Faculty of University of Cologne. Marga and Walter Boll-Foundation. Federal Ministry of Education & Research (BMBF): 01GM1515. European Rare Kidney Disease Reference Network (ERKNet).

BACKGROUND Long-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas. Given the relatively intact immune system of patients with LGGs and the slow tumor growth rate, vaccines are an attractive treatment strategy. METHODS We conducted a pilot study to evaluate the safety and immunological effects of vaccination with GBM6-AD, lysate of an allogeneic glioblastoma stem cell line, with poly-ICLC in patients with LGGs. Patients were randomized to receive the vaccines before surgery (arm 1) or not (arm 2) and all patients received adjuvant vaccines. Coprimary outcomes were to evaluate safety and immune response in the tumor. RESULTS A total of 17 eligible patients were enrolled — 9 in arm 1 and 8 in arm 2. This regimen was well tolerated with no regimen-limiting toxicity. Neoadjuvant vaccination induced upregulation of type-1 cytokines and chemokines and increased activated CD8+ T cells in peripheral blood. Single-cell RNA/T cell receptor sequencing detected CD8+ T cell clones that expanded with effector phenotype and migrated into the tumor microenvironment (TME) in response to neoadjuvant vaccination. Mass cytometric analyses detected increased tissue resident–like CD8+ T cells with effector memory phenotype in the TME after the neoadjuvant vaccination. CONCLUSION The regimen induced effector CD8+ T cell response in peripheral blood and enabled vaccine-reactive CD8+ T cells to migrate into the TME. Further refinements of the regimen may have to be integrated into future strategies. TRIAL REGISTRATION ClinicalTrials.gov NCT02549833. FUNDING NIH (1R35NS105068, 1R21CA233856), Dabbiere Foundation, Parker Institute for Cancer Immunotherapy, and Daiichi Sankyo Foundation of Life Science.

To evaluate whether the administration of prophylactic methylergonovine in addition to oxytocin in patients undergoing intrapartum cesarean birth reduces the need for additional uterotonic agents.This was a single-center, placebo-controlled, randomized trial of patients undergoing intrapartum cesarean birth. Patients were randomly allocated to receive intravenous oxytocin 300 mL/minute plus intramuscular methylergonovine 0.2 mg (1 mL) or intravenous oxytocin 300 mL/minute plus intramuscular normal saline (1 mL). The primary outcome was the receipt of additional uterotonic agents. Secondary outcomes included surgeon assessment of uterine tone, incidence of postpartum hemorrhage, quantitative blood loss, and blood transfusion. To detect a twofold decrease in the need for additional uterotonic agents (assuming a 42% baseline) with a two-sided type 1 error of 5% and power of 80%, a sample size of 76 patients per group was required.From June 2019 through February 2021, 80 patients were randomized to receive methylergonovine plus oxytocin and 80 were randomized to receive to oxytocin alone. Significantly fewer patients who were allocated to the methylergonovine group received additional uterotonic agents (20% vs 55%, relative risk [RR] 0.4, 95% CI 0.2-0.6). Participants receiving methylergonovine were more likely to have satisfactory uterine tone (80% vs 41%, RR 1.9, 95% CI 1.5-2.6), lower incidence of postpartum hemorrhage (35% vs 59%, RR 0.6, 95% CI 0.4-0.9), lower mean quantitative blood loss (967 mL vs 1,315 mL; mean difference 348, 95% CI 124-572), and a lower frequency of blood transfusion (5% vs 23%, RR 0.2, 95% CI 0.1-0.6).The administration of prophylactic methylergonovine in addition to oxytocin in patients undergoing intrapartum cesarean birth reduces the need for additional uterotonic agents.ClinicalTrials.gov, NCT03904446.

A randomized controlled study demonstrated that an optimized intraoperative infection control program targeting basic preventive measures can reduce Staphylococcus aureus transmission and surgical site infections. In this study we address potential limitations of operating room heterogeneity of infections and compliance with behavioral interventions following adoption into clinical practice.A post-implementation prospective case-cohort study.Twenty-three operating rooms at a large teaching hospital.A total of 801 surgical patients [425 (53%) women; 350 (44%) ASA 2, age 54.6 ± 15.9 years] were analyzed for the primary and 804 for the secondary outcomes.A multifaceted, evidence-based intraoperative infection control program involving hand hygiene, vascular care, and environmental cleaning improvements was implemented for 23 operating room environments. Bacterial transmission monitoring was used to provide monthly feedback for intervention optimization.S. aureus transmission (primary) and surgical site infection (secondary).The incidence of S. aureus transmission and surgical site infection before (3.5 months) and after (4.5 months) infection control optimization was assessed. Optimization was defined by a sustained reduction in anesthesia work area bacterial reservoir isolate counts. Poisson regression with robust error variances was used to estimate the incidence risk ratio (IRR) of intraoperative S. aureus transmission and surgical site infection for the independent variable of optimization.Optimization was associated with decreased S. aureus transmission [24% before (85/357) to 9% after (42/444), IRR 0.39, 95% CI 0.28 to 0.56, P .001] and surgical site infections [8% before (29/360) and 3% after (15/444) (IRR 0.42, 95% CI 0.23 to 0.77, P = .005; adjusted for American Society of Anesthesiologists' physical status, aIRR 0.45, 95% CI 0.25 to 0.82, P = .009].An optimized intraoperative infection control program targeting improvements in basic preventive measures is an effective and feasible approach for reducing S. aureus transmission and surgical site infection development.

BACKGROUND: Vegetable or plant-based sources of protein may confer health benefits in children with progressive kidney disease. Our aims were to understand the effect of the proportion of vegetable protein intake on changes in estimated GFR and to understand the effect of the proportion of vegetable protein intake on serum levels of bicarbonate, phosphorus, and potassium. METHODS: Children with baseline eGFR between 30 and 90 mL/min/1.73 m(2) were recruited from 59 centers across North America as part of the chronic kidney disease in children (CKiD) study. The percentage of dietary vegetable protein (VP%) was gathered from annual Food Frequency Questionnaires. We performed longitudinal linear mixed models to determine the effect of VP% on eGFR and longitudinal logistic mixed models to determine the effect of VP% on electrolyte balance (potassium, phosphorus, bicarbonate). RESULTS: Two thousand visits from 631 subjects. Across all dichotomized groups of children (sex, African American race, Hispanic ethnicity, glomerular etiology of CKD, hypertension, anemia, hyperkalemia, hyperphosphatemia, acidosis, BMI < 95th percentile), the median VP% was 32–35%. The longitudinal mixed model analysis did not show any effect of VP% on eGFR electrolyte (bicarbonate, phosphorus, and potassium) abnormalities (p > 0.1). CONCLUSIONS: A diverse cohort of children with CKD has a narrow and homogeneous intake of vegetable protein. Due to the low variability of plant-based protein in the cohort, there were no associations between the percentage of plant protein intake and changes in eGFR nor electrolyte balance.

BACKGROUND: Several randomised controlled trials show that maintenance of labour epidural analgesia with programmed intermittent epidural bolus reduces the maternal motor block compared with maintenance with a continuous infusion. However, these trials were usually restricted to healthy nulliparous parturients. To assess the generalisability of these randomised controlled trials to ‘real-world’ conditions, we compared maternal motor function (modified Bromage score) over time between healthy nulliparous and parous women using routinely collected quality-control data. METHODS: After ethical approval, all parturients receiving programmed intermittent epidural bolus labour analgesia between June 2013 and October 2014 were included in this prospective cohort study. Bupivacaine 0.1% with fentanyl 2 μg ml(−1) was used allowing for patient-controlled bolus every 20 min. The maternal motor function (primary outcome) was regularly assessed from insertion of the epidural catheter until delivery. RESULTS: Of the 839 parturients included, 553 (66%) were nulliparous and 286 (34%) were parous. The parous women had a shorter median duration of epidural analgesia (3 h 59 min vs 5 h 45 min) and a higher incidence of spontaneous delivery (66% vs 37%). The probability of being in a certain Bromage category at birth was similar in nulliparous and parous women in a general additive model adjusting for duration of epidural analgesia, number of rescue top-ups, and number of catheter manipulations (cumulative odds ratio: 1.18; 95% confidence interval: 0.98–1.41). Parous women required a higher time-weighted number and volume of rescue top-ups. CONCLUSIONS: The results of the randomised controlled trials on a reduced motor block with programmed intermittent epidural bolus seem generalisable to parturients typically not included in these trials.

Background and objectivesUse of regional anesthesia can result in faster recovery and better patient satisfaction. Addition of perineural adjuncts to local anesthetics may improve the duration of analgesia, but there is a paucity of data comparing them in a single randomized trial. We compared the effects of three adjuncts clonidine, dexamethasone, and buprenorphine, on the duration of analgesia of interscalene brachial plexus block.Methods160 patients, undergoing elective shoulder surgery, were randomized to four groups to receive an interscalene block with one of the following solutions: ropivacaine alone, ropivacaine with clonidine 75 µg, ropivacaine with dexamethasone 8 mg, or ropivacaine with buprenorphine 300 µg. The primary outcome variable was the duration of analgesia; secondary outcome measures were time to onset of the block, and the duration of sensory and motor blocks.ResultsThere was no statistically significant difference in the total analgesia time among the four groups; p=0.11. The pairwise comparison in analgesic time and 99% CI were: control versus clonidine (−1.94 hours (−7.33 to 3.12)), control versus dexamethasone (−4.16 hours (−9.50 to 0.58)) and control versus buprenorphine (−1.1 hours (−5.34 to 3.23)). There was no differences in block set-up time, or total sensory and motor block duration among the groups.ConclusionThere was no significant improvement in the duration of analgesia with addition of any of the three adjuncts to interscalene blocks. However, there was a larger than expected variability in patient response, hence the study may have been underpowered for the primary outcome.

The fabrication of hydrophilic porous hydrogel, with high mechanical strength and good uptake capacity is desirable for a broad range of applications such as drug delivery and liquid sensors. The usual methods are limited to the production of structures with high density of covalently crosslinked networks that restricts the polymer chain rearrangement, resulting in non-uniformed pore size distribution. Covalent networks also limit the activity of functional groups and influence the uptake properties of the polymer. In this study, we proposed simple cyclic cryogelation for the fabrication of hydrogels with uniform pore sizes via controlling the micellization and crystal formation. The chitosan based hydrogels ionically crosslinked with 8 % (w/v) of tripoli phosphate sodium (TPP) displayed high Young’s modulus (63 MPa) after cyclic freezethawing. The liquid uptake capacity of the samples treated with 8 % (w/v) TPP solution at pH 4 showed a slight decrease of about 29 % in comparison to that of non-cyclic processed samples (36 %).

BACKGROUND Gender inequity is still prevalent in today's medical workforce. Previous studies have investigated the status of women in academic anesthesiology. The objective of this study is to provide a current update on the status of women in academic anesthesiology. We hypothesized that while the number of women in academic anesthesiology has increased in the past 10 years, major gender disparities continue to persist, most notably in leadership roles. METHODS Medical student, resident, and faculty data were obtained from the Association of American Medical Colleges. The number of women in anesthesiology at the resident and faculty level, the distribution of faculty academic rank, and the number of women chairpersons were compared across the period from 2006 to 2016. The gender distribution of major anesthesiology journal editorial boards and data on anesthesiology research grant awards, among other leadership roles, were collected from websites and compared to data from 2005 and 2006. RESULTS The number (%) of women anesthesiology residents/faculty has increased from 1570 (32%)/1783 (29%) in 2006 to 2145 (35%)/2945 (36%) in 2016 (P = .004 and P < .001, respectively). Since 2006, the odds that an anesthesiology faculty member was a woman increased approximately 2% per year, with an estimated odds ratio of 1.02 (95% confidence interval, 1.014-1.025; P < .001). In 2015, the percentage of women anesthesiology full professors (7.4%) was less than men full professors (17.3%) (difference, -9.9%; 95% confidence interval of the difference, -8.5% to -11.3%; P < .001). The percentage of women anesthesiology department chairs remained unchanged from 2006 to 2016 (12.7% vs 14.0%) (P = .75). To date, neither Anesthesia & Analgesia nor Anesthesiology has had a woman Editor-in-Chief. The percentage of major research grant awards to women has increased significantly from 21.1% in 1997-2007 to 31.5% in 2007-2016 (P = .02). CONCLUSIONS Gender disparities continue to exist at the upper levels of leadership in academic anesthesiology, most importantly in the roles of full professor, department chair, and journal editors. However, there are some indications that women may be on the path to leadership parity, most notably, the growth of women in anesthesiology residencies and faculty positions and increases in major research grants awarded to women.

The fabrication of patient-specific scaffolds for bone substitutes is possible through extrusion-based 3D printing of calcium phosphate cements (CPC) which allows the generation of structures with a high degree of customization and interconnected porosity. Given the brittleness of this clinically approved material, the stability of open-porous scaffolds cannot always be secured. Herein, a multi-technological approach allowed the simultaneous combination of CPC printing with melt electrowriting (MEW) of polycaprolactone (PCL) microfibers in an alternating, tunable design in one automated fabrication process. The hybrid CPC+PCL scaffolds with varying CPC strand distance (800–2000 µm) and integrated PCL fibers featured a strong CPC to PCL interface. While no adverse effect on mechanical stiffness was detected by the PCL-supported scaffold design; the microfiber integration led to an improved integrity. The pore distance between CPC strands was gradually increased to identify at which critical CPC porosity the microfibers would have a significant impact on pore bridging behavior and growth of seeded cells. At a CPC strand distance of 1600 µm, after 2 weeks of cultivation, the incorporation of PCL fibers led to pore coverage by a human mesenchymal stem cell line and an elevated proliferation level of murine pre-osteoblasts. The integrated fabrication approach allows versatile design adjustments on different levels.

There are many ways to characterize biomaterials, be it physically, chemically, or biologically. This chapter focuses on the surface and biological characterization of biomaterials. Techniques that are commonly used in these two areas are described and examples provided to demonstrate their relevance to biomaterials research. Microscopy techniques such as scanning and transmission electron microscopy that are widely used to characterize surface properties of biomaterials have been included. The second part of the chapter covers methods such as cell viability and functional assays as quantitative measures along with immunohistochemistry and histology as qualitative techniques to investigate the interaction of cells with biomaterials.

To analyze racial and ethnic disparities in failure to rescue (ie, death) associated with severe maternal morbidity and describe temporal trends.This was a retrospective cohort study using administrative data. Data for delivery hospitalizations with severe maternal morbidity, as defined by the Centers for Disease Control and Prevention, were abstracted from the 1999-2017 National Inpatient Sample. Race and ethnicity were categorized into non-Hispanic White (reference), non-Hispanic Black, Hispanic, other, and missing. The outcome was failure to rescue from severe maternal morbidity. Disparities were assessed using the failure-to-rescue rate ratio (ratio of the failure-to-rescue rate in the racial and minority group to the failure-to-rescue rate in White women), adjusted for patient and hospital characteristics. Temporal trends in severe maternal morbidity and failure to rescue were assessed.During the study period, 73,934,559 delivery hospitalizations were identified, including 993,864 with severe maternal morbidity (13.4/1,000; 95% CI 13.3-13.5). Among women with severe maternal morbidity, 4,328 died (4.3/1,000; 95% CI 4.2-4.5). The adjusted failure-to-rescue rate ratio was 1.79 (95% CI 1.77-1.81) for Black women, 1.39 (95% CI 1.37-1.41) for women of other race and ethnicity, 1.43 (95% CI 1.42-1.45) for women with missing race and ethnicity data, and 1.08 (95% CI 1.06-1.09) for Hispanic women. During the study period, the severe maternal morbidity rate increased significantly in each of the five racial and ethnic groups but started declining in 2012. Meanwhile, the failure-to-rescue rate decreased significantly during the entire study period.Despite improvement over time, failure to rescue from severe maternal morbidity remains a major contributing factor to excess maternal mortality in racial and ethnic minority women.

Background Up to 84% of women who undergo operative vaginal delivery receive neuraxial analgesia. However, little is known about the association between neuraxial analgesia and neonatal morbidity in women who undergo operative vaginal delivery. The authors hypothesized that neuraxial analgesia is associated with a reduced risk of neonatal morbidity among women undergoing operative vaginal delivery. Methods Using United States birth certificate data, the study identified women with singleton pregnancies who underwent operative vaginal (forceps- or vacuum-assisted delivery) in 2017. The authors examined the relationships between neuraxial labor analgesia and neonatal morbidity, the latter defined by any of the following: 5-min Apgar score less than 7, immediate assisted ventilation, assisted ventilation greater than 6 h, neonatal intensive care unit admission, neonatal transfer to a different facility within 24 h of delivery, and neonatal seizure or serious neurologic dysfunction. The authors accounted for sociodemographic and obstetric factors as potential confounders in their analysis. Results The study cohort comprised 106,845 women who underwent operative vaginal delivery, of whom 92,518 (86.6%) received neuraxial analgesia. The proportion of neonates with morbidity was higher in the neuraxial analgesia group than the nonneuraxial group (10,409 of 92,518 [11.3%] vs. 1,271 of 14,327 [8.9%], respectively; P < 0.001). The unadjusted relative risk was 1.27 (95% CI, 1.20 to 1.34; P < 0.001); after accounting for confounders using a multivariable model, the adjusted relative risk was 1.19 (95% CI, 1.12 to 1.26; P < 0.001). In a post hoc analysis, after excluding neonatal intensive care unit admission and neonatal transfer from the composite outcome, the effect of neuraxial analgesia on neonatal morbidity was not statistically significant (adjusted relative risk, 1.07; 95% CI, 1.00 to 1.16; P = 0.054). Conclusions In this population-based cross-sectional study, a neonatal benefit of neuraxial analgesia for operative vaginal delivery was not observed. Confounding by indication may explain the observed association between neuraxial analgesia and neonatal morbidity, however this dataset was not designed to evaluate such considerations. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Objectives: To conduct a systematic review and meta-analysis to assess whether individuals with nonsyndromic orofacial clefts (OCs) display a higher frequency of dental anomalies (DAs) when compared with individuals without OCs. Methods: A literature search of indexed databases (PubMed, Cochrane, Web of Science, Embase, Scopus, and LILACS) was conducted without language restriction up to and including February 1, 2020. Cross-referencing was used to further identify articles. Several cleft teams across the United States and Europe were contacted to obtain unpublished data. The eligibility criteria were observational studies with original data that statistically compared individuals with OC without syndromes and those without OC on any type of DA in primary and/or permanent dentition. Random effects meta-analysis through the Mantel-Haenszel estimator was used to evaluate the association between OC and DA based on odds ratios (ORs) with 95% confidence intervals (CIs). Results: The literature search generated 933 records, and 75 full-text articles were reviewed. Twenty-six studies encompassing 15,213 individuals met the inclusion criteria. The meta-analysis revealed statistically significant associations between OC and agenesis (OR, 14.2; 95% CI, 9.4 to 21.3), supernumerary teeth (OR, 5.7; 95% CI, 3.3 to 9.7), developmental enamel defects (OR, 5.6; 95% CI, 3.5 to 9.0), microdontia (OR, 14.8; 95% CI, 4.0 to 54.6), peg-shaped anterior teeth (OR, 12.2; 95% CI, 3.6 to 41.2), taurodontism (OR, 1.7; 95% CI, 1.0 to 2.7), tooth malposition and/or transposition (OR, 5.6; 95% CI, 2.8 to 11.5), tooth rotation (OR, 3.2; 95% CI, 1.3 to 8.2), and tooth impaction (OR, 3.6; 95% CI, 1.1 to 12.2). The OR estimates of the reviewed studies exhibited significant heterogeneity ( P < 0.0001). No association was observed between OC and fusion and/or gemination. Conclusion: Within the limitations of this study, the available evidence suggests that individuals with OCs are more likely to present with a range of DAs than their unaffected peers. Knowledge Transfer Statement: The findings of the current review suggest that individuals with orofacial clefts (OCs) are more likely to present with a range of dental anomalies than their unaffected peers. Understanding the association between OCs and dental anomalies is essential in guiding clinicians during treatment-planning procedures and is important in raising our awareness of the possible need for future dental treatment for patients with OCs.

Assessing the role of lactogenic hormones in human mammary gland development is limited due to issues accessing tissue samples and so development of a human in vitro three-dimensional mammosphere model with functions similar to secretory alveoli in the mammary gland can aid to overcome this shortfall. In this study, a mammosphere model has been characterised using human mammary epithelial cells grown on either mouse extracellular matrix or agarose and showed insulin is essential for formation of mammospheres. Insulin was shown to up-regulate extracellular matrix genes. Microarray analysis of these mammospheres revealed an up-regulation of differentiation, cell-cell junctions, and cytoskeleton organisation functions, suggesting mammosphere formation may be regulated through ILK signalling. Comparison of insulin and IGF-1 effects on mammosphere signalling showed that although IGF-1 could induce spherical structures, the cells did not polarise correctly as shown by the absence of up-regulation of polarisation genes and did not induce the expression of milk protein genes. This study demonstrated a major role for insulin in mammary acinar development for secretory differentiation and function indicating the potential for reduced lactational efficiency in women with obesity and gestational diabetes.

Tissue growth in bioscaffolds can be influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in a 3D printed scaffold by analysing experiments with a mathematical model. Experimentally, the new tissue infills the pore continually from the pore perimeter under strong curvature control, which leads to rounding off of the initial pore shape. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge the pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction--diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new cellular tissue in the model grows at a rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis therefore suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic cell proliferation and cell diffusion processes. The rates of these processes are unaffected by pore geometry, and can be predicted by simple reaction--diffusion models of cells that have robust, consistent behaviours.

Prophylactic epidural morphine administration after unintentional dural puncture with a large-bore needle has been shown to decrease the incidence of post-dural puncture headache. The authors hypothesized that prophylactic administration of intrathecal morphine would decrease the incidence of post-dural puncture headache and/or need for epidural blood patch after unintentional dural puncture.Parturients with an intrathecal catheter in situ after unintentional dural puncture with a 17-g Tuohy needle during intended epidural catheter placement for labor analgesia were enrolled in this randomized, double-blind trial. After delivery, subjects were randomized to receive intrathecal morphine 150 µg or normal saline. The primary outcome was the incidence of post-dural puncture headache. Secondary outcomes included onset, duration, and severity of post-dural puncture headache, the presence of cranial nerve symptoms and the type of treatment the patient received.Sixty-one women were included in the study. The incidence of post-dural puncture headache was 21 of 27 (78%) in the intrathecal morphine group and 27 of 34 (79%) in the intrathecal saline group (difference, -1%; 95% CI, -25% to 24%). There were no differences between groups in the onset, duration, or severity of headache, or presence of cranial nerve symptoms. Epidural blood patch was administered to 10 of 27 (37%) of subjects in the intrathecal morphine and 11 of 21 (52%) of the intrathecal saline group (difference 15%; 95% CI, -18% to 48%).The present findings suggest that a single prophylactic intrathecal morphine dose of 150 µg administered shortly after delivery does not decrease the incidence or severity of post-dural puncture headache after unintentional dural puncture. This study does not support the clinical usefulness of prophylactic intrathecal morphine after an unintentional dural puncture.

We document an overall trend of reduced risk exposure in the target date fund (TDF) market which explains the better performance of TDFs in the COVID-19 than the 2008 crisis. The overall shift of the glide path towards less equity allocation causes TDFs to achieve significantly less during normal times when the market exhibit positive returns. We find that the shift is driven by the TDF series investing more in equities in the early period, consistent with TDFs catering to the market demand for lower risk exposure post the crisis. In addition, TDF shifters do not exhibit more idiosyncratic risk taking. Neither is aggregate glide path shift informative about subsequent equity market returns.

Bone morphogenetic proteins (BMPs) are osteogenic growth factors frequently incorporated into biomedical devices to encourage the formation and regeneration of bone. They have played an important role in the development of tissue engineering, regenerative medicine, and, more recently, biofabrication strategies for the treatment of bone loss as a result of disease, trauma, or congenital abnormality. Current metallic bone implants provide load-bearing mechanical properties but are not osteoinductive, failing to instigate bone formation and infiltration into the implant for effective regeneration. Following regulatory approval for spinal fusion products in the early 2000s, BMPs peaked in interest over the next decade for the treatment of a range of bone conditions. However, various concerns surrounding on- and off-label BMPs use in the early 2010s demonstrated a lack of translational understanding. We have now reached an era where the future of bone regeneration device development aims to minimize dosages, incorporate advanced controlled-release patterns, or potentially avoid the use of BMPs altogether. These advanced techniques aim to maintain the same, if not improved efficacy of devices without the costs and risks associated with BMP use. This chapter discusses BMPs past and future applications at a turning point in its use for osteoinductivity in biofabrication devices.

To address the increasing demand for safe and effective treatment options for pelvic organ prolapse (POP) due to the worldwide ban of the traditional polypropylene meshes, this study introduced degradable polycaprolactone (PCL)/polyethylene glycol (PEG) composite meshes fabricated with melt-electrowriting (MEW). Two PCL/PEG mesh groups: 90:10 and 75:25 (PCL:PEG, wt%) were fabricated and characterized for their degradation rate and mechanical properties, with PCL meshes used as a control. The PCL/PEG composites showed controllable degradation rates by adjusting the PEG content and produced mechanical properties, such as maximal forces, that were higher than PCL alone. The antibacterial properties of the meshes were elicited by coating them with a commonly used antibiotic: azithromycin. Two dosage levels were used for the coating: 0.5 mg and 1 mg per mesh, and both dosage levels were found to be effective in suppressing the growth of S. aureus bacteria. The biocompatibility of the meshes was assessed using human immortalized adipose derived mesenchymal stem cells (hMSC). In vitro assays were used to assess the cell viability (LIVE/DEAD assay), cell metabolic activity (alamarBlue assay) and cell morphology on the meshes (fluorescent and electron microscopy). The cell attachment was found to decrease with increased PEG content. The freshly drug-coated meshes showed signs of cytotoxicity during the cell study process. However, when pre-released for 14 days in phosphate buffered saline, the initial delay in cell attachment on the drug-coated mesh groups showed full recovery at the 14-day cell culture time point. These results indicated that the PCL/PEG meshes with antibiotics coating will be an effective anti-infectious device when first implanted into the patients, and, after about 2 weeks of drug release, the mesh will be supporting cell attachment and proliferation. These meshes demonstrated a potential effective treatment option for POP that may circumvent the issues related to the traditional polypropylene meshes.