Recombinant erythropoietin for the treatment of iron deficiency anemia in pregnancy: A systematic review.

BACKGROUND: Treatment options for severe, refractory iron deficiency anemia are limited in pregnancy. OBJECTIVE: To review the available literature on the use of recombinant erythropoietin in the treatment of iron deficiency anemia in pregnancy. SEARCH STRATEGY: An electronic search of seven databases from inception to March 2022 was performed using a combination of keywords. SELECTION CRITERIA: We included all randomized controlled or observational studies of pregnant patients with iron deficiency anemia who received recombinant erythropoietin or control. The primary outcome was a change in hematologic parameters (hemoglobin or hematocrit) after treatment. Studies were appraised using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. DATA COLLECTION AND ANALYSIS: Data were summarized using narrative synthesis and descriptive statistics as appropriate. This study was registered with PROSPERO, CRD42022313328. MAIN RESULTS: Of 234 studies screened, five studies met the inclusion criteria and had sufficient data for analysis (n = 103 recombinant erythropoietin and n = 104 controls). All patients in the intervention group received iron supplementation (intravenous or oral) in addition to recombinant erythropoietin. All patients in the control group received iron supplementation (intravenous or oral) alone. As the result of variance between studies in inclusion criteria, the timing of repeat blood draws, and data reporting, a meta-analysis could not be performed. Three studies found that serial recombinant erythropoietin combined with iron supplementation was more effective at raising hematologic laboratory parameters (hemoglobin or hematocrit) than iron alone. One study reported no difference in hemoglobin or hematocrit levels between groups at day 28. However, patients in this study only received one dose of recombinant erythropoietin, whereas those in the other studies received serial doses. Another study also found no difference in hemoglobin levels by day 28, but patients in the recombinant erythropoietin group had lower hemoglobin levels at baseline and a more rapid rise in hemoglobin than iron alone. This is demonstrated by a more significant rise in hemoglobin at day 11 in the recombinant erythropoietin group than in the control group. CONCLUSIONS: Serial recombinant erythropoietin administration and iron supplementation may be more effective at treating refractory iron deficiency anemia in pregnancy than iron supplementation alone.

Enhancing Laryngoscopy Mastery: The Impact of Autonomous Practice with Feedback-Providing Simulators.

Mastery learning with fixed end points and variable training time leads to more consistent expertise but is difficult to implement. Here we piloted mastery learning of laryngoscopy with independent practice. 35 learners participated in independent mastery learning on a manikin that provides automated performance feedback. A pre- and postpractice assessment of intubation skills was completed. After an average of 21 minutes of open practice, the percentage of subjects that met mastery criteria improved from 24% to 89% (P < .05). Independent intubation practice with manikin feedback facilitated mastery learning, enhanced procedural education, and may impact clinical care.

Stereoselective convergent total synthesis of oxylipins.

We synthesized stereoselectively four stereoisomers of oxylipins (1a-d) by a convergent approach based on chiral catalysis. The synthetic approach involved sequential assembly of two key fragments - ene-diol and allyl alcohol - for an intended convergent cross-metathesis reaction to join these fragments. The key steps include Sharpless kinetic resolution, asymmetric dihydroxylation and Grubbs cross-metathesis. The characterization of the synthesized oxylipins revealed spectroscopic data that were consistent with previously reported values.

A Narrative Review of Ultrasound-Guided and Landmark-based Percutaneous Cryoneurolysis for the Management of Acute and Chronic Pain.

PURPOSE OF REVIEW: Cryoneurolysis refers to the process of reversibly ablating peripheral nerves with extremely cold temperatures to provide analgesia for weeks to months. With ultrasound-guidance or landmark-based techniques, it is an effective modality for managing both acute and chronic pain. In this review, we summarize the reported literature behind its potential applications and efficacy. RECENT FINDINGS: Here, we summarize several studies (from case reports to clinical trials) describing the use of ultrasound-guided and landmark-based cryoneurolysis for acute and chronic pain. Acute pain indications included pain related to knee arthroplasty, limb amputations, mastectomies, shoulder surgery, rib fractures, and burn. Chronic pain indications included chronic knee pain (due to osteoarthritis), shoulder pain, painful neuropathies, postmastectomy pain syndrome, phantom limb pain, facial pain/headaches, foot/ankle pain, inguinal pain, and sacroiliac joint pain. For both acute and chronic pain indications, more high quality randomized controlled clinical trials are needed to definitively assess the efficacy of cryoneurolysis versus other standard therapies for a multitude of pain conditions.

Cord blood troponin I levels: biomarker evidence of fetal cardiac injury in intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy has been linked to sudden stillbirth. The suddenness of the stillbirths in these cases have led clinicians to suspect that the pathogenesis of stillbirth in women with intrahepatic cholestasis of pregnancy is not related to asphyxia but rather to an undefined etiology. One leading hypothesis relates certain bile acid metabolites to myocardial injury. OBJECTIVE: The purpose of this study was to determine whether cord blood troponin I levels are increased in fetuses born to mothers with a diagnosis of intrahepatic cholestasis of pregnancy. STUDY DESIGN: A prospective, case-control study was performed at a single institution between 2017 to 2019 in which 87 pregnant patients with a diagnosis of intrahepatic cholestasis of pregnancy (total bile acids ≥10 µmol/L) were enrolled as cases and 122 randomly selected pregnant patients (asymptomatic with intrapartum total bile acids <10 µmol/L) were enrolled as controls. Cord blood troponin I levels were measured at delivery in both groups using a commercially available chemiluminescent immunoassay. Values ≤0.04 ng/mL were considered negative. Values >0.04 ng/mL were considered positive. The primary outcome was the presence of elevated troponin levels in both cases and controls as a surrogate marker for cardiac status. Our secondary outcomes included neonatal intensive care unit stay, low Apgar scores, neonatal acidosis, and hypoxia indicated by cord blood pH and base excess levels at the time of birth. Chi square and t tests were performed to compare social and obstetrical variables. A P value of <.05 was considered significant. A stratification by total bile acids range of <40 µmol/L, 40 to 100 µmol/L, and >100 µmol/L was performed to assess the relationship between the different severities of intrahepatic cholestasis of pregnancy (by risk of fetal demise with those with total bile acids of >100 µmol/L considered at greatest risk) and the likelihood of a positive troponin I result. Finally, a logistic regression analysis was performed to determine if levels of ≥10 µmol/L were associated with elevated troponin levels. RESULTS: The mean gestational age at delivery was 38.96±1.47 and 37.71±1.59 weeks of gestation in the controls and cases respectively (P<.001). The mean total bile acids values were 5.2±1.28 ng/mL and 43.2±40.62 ng/mL in the controls and cases respectively (P<.001). Cord blood troponin I was positive in 15 of 122 (12.30%) controls and in 20 of 87 (22.99%) cases. (P<.001). When further stratified by total bile acids levels of <40, 40 to 100, and >100 µmol/L, we found a positive correlation between higher total bile acids levels and a positive troponin I test (P=.002). When controlling for gestational age at delivery, maternal age, and body mass index, higher total bile acids levels were associated with a positive troponin I level (adjusted odds ratio, 1.015; 95% confidence interval, 1.004-1.026). CONCLUSION: Elevated troponin I was more likely to be found in patients with intrahepatic cholestasis of pregnancy than in those without intrahepatic cholestasis of pregnancy. When stratified by total bile acids levels, a positive troponin I level was more likely to be found with higher levels of total bile acids. In addition, as total bile acids levels increased, they were more likely to be associated with a positive troponin I level. Although there were no stillbirths in our cohort, our findings suggest a potential relationship between cardiac injury and high levels of total bile acids demonstrated by the presence of elevated troponin I levels in cord blood at the time of birth.

A novel mathematical template for developing fDOM probe fluorescence signal correction models for freshwaters.

The reliable application of field deployable fluorescent dissolved organic matter (fDOM) probes is hindered by several influencing factors which need to be compensated. This manuscript describes the corrections of temperature, pH, turbidity and inner filter effect on fluorescence signal of a commercial fDOM probe (fDOMs). For this, Australian waters with wide ranging qualities were selected, e.g. dissolved organic carbon (DOC) ranging from ∼1 to ∼30 mg/L, specific UV absorbance at 254 nm from ∼1 to ∼6 L/m/mg and turbidity from ∼1 to ∼ 350 FNU. Laboratory-based model calibration experiments (MCEs) were performed. A model template was developed and used for the development of the correction models. For each factor, data generated through MCEs were used to determine model coefficient (α) values by fitting the generated model to the experimental data. Four discrete factor models were generated by determination of a factor-specific α value. The α values derived for each water of the MCEs subset were consistent for each factor model. This indicated generic nature of the four α values across wide-ranging water qualities. High correlation between fDOMs and DOC were achieved after applying the four-factor compensation models to new data (r, 0.96, p < 0.05). Also, average biases (and %) between DOC predicted through fDOMs and actual DOC were decreased by applying the four-factor compensation model (from 3.54 (60.9%) to 1.28 (16.7%) mg/L DOC). These correction models were incorporated into a Microsoft EXCEL-based software termed EXOf-Correct for ready-to-use applications.

A simple and scalable zebrafish model of Sonic hedgehog medulloblastoma.

Medulloblastoma (MB) is the most common malignant brain tumor in children and is stratified into three major subgroups. The Sonic hedgehog (SHH) subgroup represents ∼30% of all MB cases and has significant survival disparity depending upon TP53 status. Here, we describe a zebrafish model of SHH MB using CRISPR to create mutant ptch1, the primary genetic driver of human SHH MB. In these animals, tumors rapidly arise in the cerebellum and resemble human SHH MB by histology and comparative onco-genomics. Similar to human patients, MB tumors with loss of both ptch1 and tp53 have aggressive tumor histology and significantly worse survival outcomes. The simplicity and scalability of the ptch1-crispant MB model makes it highly amenable to CRISPR-based genome-editing screens to identify genes required for SHH MB tumor formation in vivo, and here we identify the gene encoding Grk3 kinase as one such target.

K2S2O8-Mediated or Azobisisobutyronitrile-Catalyzed Regioselective Aerobic Oxidative Cleavage of 1-Arylbutadienes to Cinnamaldehydes.

This work reveals the regioselective oxidative cleavage of 1-arylbutadienes to cinnamaldehydes mediated by K2S2O8 or catalyzed by azobisisobutyronitrile, a very common free radical initiator, in an easy to handle, simple procedure and free of transition metals. This approach demonstrates excellent regioselectivity, mild reaction conditions, and compatibility with a broad range of functional groups (45 examples).

Glucose-6-phosphate dehydrogenase deficiency as a cause for nonimmune hydrops fetalis and severe fetal anemia: A systematic review.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder that predisposes individuals to hemolysis due to an inborn error of metabolism. We performed a systematic literature review to evaluate G6PD deficiency as a possible etiology of nonimmune hydrops fetalis (NIHF) and severe fetal anemia. METHODS: PubMed, OVID Medline, Scopus, and clinicaltrials.gov were queried from inception until 31 April 2023 for all published cases of NIHF and severe fetal anemia caused by G6PD deficiency. Keywords included "fetal edema," "hydrops fetalis," "glucose 6 phosphate dehydrogenase deficiency," and "fetal anemia." Cases with workup presuming G6PD deficiency as an etiology for NIHF and severe fetal anemia were included. PRISMA guidelines were followed. RESULTS: Five cases of G6PD-related NIHF and one case of severe fetal anemia were identified. Four fetuses (4/6, 66.7%) were male and two fetuses (2/6, 33.3%) were female. Mean gestational age at diagnosis of NIHF/anemia and delivery was 32.2 ± 4.9 and 35.7 ± 2.4 weeks, respectively. Four cases (66.7%) required a cordocentesis for fetal transfusion, and two cases (33.3%) received blood transfusions immediately following delivery. Among the four multigravida cases, two (50%) noted previous pregnancies complicated by neonatal anemia. When reported, the maternal cases included two G6PD deficiency carrier patients and two G6PD-deficient patients. Exposures to substances known to cause G6PD deficiency-related hemolysis occurred in 3/6 (50%) cases. CONCLUSION: Six cases of NIHF/severe fetal anemia were associated with G6PD deficiency. While G6PD deficiency is an X-linked recessive condition, female fetuses can be affected. Fetal G6PD deficiency testing can be considered if parental history indicates, particularly if the standard workup for NIHF is negative.

Associations Between Stroke Type, Ischemic Stroke Subtypes, and Post-Stroke Cognitive Trajectories.

Background: It is unclear how post-stroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic, hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, cryptogenic/other determined etiology), and post-stroke cognitive decline. Methods: This pooled cohort analysis from four US cohort studies (1971-2019) identified 1,143 dementia-free individuals with acute stroke during follow-up: 1,061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, 30.8% Black. Median age at stroke was 74.1 (IQR, 68.6, 79.3) years. Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median follow-up for the primary outcome was 6.0 (IQR, 3.2, 9.2) years. Linear mixed-effects models estimated changes in cognition after stroke. Results: On average, the initial post-stroke global cognition score was 50.78 points (95% CI, 49.52, 52.03) in ischemic stroke survivors and did not differ in hemorrhagic stroke survivors (difference, -0.17 points [95% CI, -1.64, 1.30]; P=0.82) after adjusting for demographics and pre-stroke cognition. On average, ischemic stroke survivors showed declines in global cognition, executive function, and memory. Post-stroke declines in global cognition, executive function, and memory did not differ between hemorrhagic and ischemic stroke survivors. 955 ischemic strokes had subtypes: 200 (20.9%) cardioembolic, 77 (8.1%) large artery atherosclerotic, 207 (21.7%) lacunar/small vessel, 471 (49.3%) cryptogenic/other determined etiology. On average, small vessel stroke survivors showed declines in global cognition and memory, but not executive function. Initial post-stroke cognitive scores and cognitive declines did not differ between small vessel survivors and survivors of other ischemic stroke subtypes. Post-stroke vascular risk factor levels did not attenuate associations. Conclusion: Stroke survivors had cognitive decline in multiple domains. Declines did not differ by stroke type or ischemic stroke subtype.

Association of amisulpride and recovery room length of stay among patients with postoperative nausea and vomiting following outpatient surgery.

STUDY OBJECTIVE: Postoperative nausea and vomiting (PONV) is a common sequela of surgery in patients undergoing general anesthesia. Amisulpride has shown promise in its ability to treat PONV. The objective of this study was to determine if amisulpride is associated with significant changes in PACU efficiency within a fast-paced ambulatory surgery center. METHODS: This was a retrospective cohort study of 816 patients at a single ambulatory surgery center who experienced PONV between 2018 and 2023. The two cohorts analyzed were patients who did or did not have amisulpride among their anti-emetic regimens in the PACU during two distinct time periods (before and after amisulpride was introduced). The primary outcome of the study was PACU length of stay. Both unmatched analysis and a linear multivariable mixed-effects model fit by restricted maximum likelihood (random effect being surgical procedure) were used to analyze the association between amisulpride and PACU length of stay. We performed segmented regression to account for cohorts occurring during two time periods. RESULTS: Unmatched univariate analysis revealed no significant difference in PACU length of stay (minutes) between the amisulpride and no amisulpride cohorts (115 min vs 119 min, respectively; P = 0.07). However, when addressing confounders by means of the mixed-effects multivariable segmented regression, the amisulpride cohort was associated with a statistically significant reduction in PACU length of stay by 26.1 min (P < 0.001). CONCLUSIONS: This study demonstrated that amisulpride was associated with a significant decrease in PACU length of stay among patients with PONV in a single outpatient surgery center. The downstream cost-savings and operational efficiency gained from this drug's implementation may serve as a useful lens through which this drug's widespread implementation may further be rationalized.

Optimal Donor Selection Across Multiple Outcomes For Hematopoietic Stem Cell Transplantation By Bayesian Nonparametric Machine Learning.

Allogeneic hematopoietic cell transplantation (HCT) is one of the only curative treatment options for patients suffering from life-threatening hematologic malignancies; yet, the possible adverse complications can be serious even fatal. Matching between donor and recipient for 4 of the HLA genes is widely accepted and supported by the literature. However, among 8/8 allele matched unrelated donors, there is less agreement among centers and transplant physicians about how to prioritize donor characteristics like additional HLA loci (DPB1 and DQB1), donor sex/parity, CMV status, and age to optimize transplant outcomes. This leads to varying donor selection practice from patient to patient or via center protocols. Furthermore, different donor characteristics may impact different post transplant outcomes beyond mortality, including disease relapse, graft failure/rejection, and chronic graft-versus-host disease (components of event-free survival, EFS). We develop a general methodology to identify optimal treatment decisions by considering the trade-offs on multiple outcomes modeled using Bayesian nonparametric machine learning. We apply the proposed approach to the problem of donor selection to optimize overall survival and event-free survival, using a large outcomes registry of HCT recipients and their actual and potential donors from the Center for International Blood and Marrow Transplant Research (CIBMTR). Our approach leads to a donor selection strategy that favors the youngest male donor, except when there is a female donor that is substantially younger.

Asymmetric total syntheses of aspilactonol F and aspiketolactonol and synthetic studies toward diplofuranoxin.

The first asymmetric total synthesis of C9 polyketides, aspilactonol F and aspiketolactonol has been achieved. Ring-closing-metathesis has been employed as the key step in the synthesis. The total synthesis of aspilactonol F and aspiketolactonol was accomplished in 8 and 10 steps, in good overall yields of 28% and 24%, respectively, with only four column purifications for the former. A common strategy for the concise synthesis of the key intermediate of diplofuranoxin is also presented.

Development and validation of the Michigan Chronic Disease Simulation Model (MICROSIM).

Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.

Effect of Population-Level Blood Pressure Treatment Strategies on Cardiovascular and Cognitive Outcomes.

BACKGROUND: The large and increasing number of adults living with dementia is a pressing societal priority, which may be partially mitigated through improved population-level blood pressure (BP) control. We explored how tighter population-level BP control affects the incidence of atherosclerotic cardiovascular disease (ASCVD) events and dementia. METHODS: Using an open-source ASCVD and dementia simulation analysis platform, the Michigan Chronic Disease Simulation Model, we evaluated how optimal implementation of 2 BP treatments based on the Eighth Joint National Committee recommendations and SPRINT (Systolic Blood Pressure Intervention Trial) protocol would influence population-level ASCVD events, global cognitive performance, and all-cause dementia. We simulated 3 populations (usual care, Eighth Joint National Committee based, SPRINT based) using nationally representative data to annually update risk factors and assign ASCVD events, global cognitive performance scores, and dementia, applying different BP treatments in each population. We tabulated total ASCVD events, global cognitive performance, all-cause dementia, optimal brain health, and years lived in each state per population. RESULTS: Optimal implementation of SPRINT-based BP treatment strategy, compared with usual care, reduced ASCVD events in the United States by ≈77 000 per year and produced 0.4 more years of stroke- or myocardial infarction-free survival when averaged across all Americans. Population-level gains in years lived free of ASCVD events were greater for SPRINT-based than Eighth Joint National Committee-based treatment. Survival and years spent with optimal brain health improved with optimal SPRINT-based BP treatment implementation versus usual care: the average patient with hypertension lived 0.19 additional years and 0.3 additional years in optimal brain health. SPRINT-based BP treatment increased the number of years lived without dementia (by an average of 0.13 years/person with hypertension), but increased the total number of individuals with dementia, mainly through more adults surviving to advanced ages. CONCLUSIONS: Tighter BP control likely benefits most individuals but is unlikely to reduce dementia prevalence and might even increase the number of older adults living with dementia.

Cumulative Systolic Blood Pressure and Incident Stroke Type Variation by Race and Ethnicity.

Importance: Stroke risk varies by systolic blood pressure (SBP), race, and ethnicity. The association between cumulative mean SBP and incident stroke type is unclear, and whether this association differs by race and ethnicity remains unknown. Objective: To examine the association between cumulative mean SBP and first incident stroke among 3 major stroke types-ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH)-and explore how these associations vary by race and ethnicity. Design, Setting, and Participants: Individual participant data from 6 US longitudinal cohorts (January 1, 1971, to December 31, 2019) were pooled. The analysis was performed from January 1, 2022, to January 2, 2024. The median follow-up was 21.6 (IQR, 13.6-31.8) years. Exposure: Time-dependent cumulative mean SBP. Main Outcomes and Measures: The primary outcome was time from baseline visit to first incident stroke. Secondary outcomes consisted of time to first incident IS, ICH, and SAH. Results: Among 40 016 participants, 38 167 who were 18 years or older at baseline with no history of stroke and at least 1 SBP measurement before the first incident stroke were included in the analysis. Of these, 54.0% were women; 25.0% were Black, 8.9% were Hispanic of any race, and 66.2% were White. The mean (SD) age at baseline was 53.4 (17.0) years and the mean (SD) SBP at baseline was 136.9 (20.4) mm Hg. A 10-mm Hg higher cumulative mean SBP was associated with a higher risk of overall stroke (hazard ratio [HR], 1.20 [95% CI, 1.18-1.23]), IS (HR, 1.20 [95% CI, 1.17-1.22]), and ICH (HR, 1.31 [95% CI, 1.25-1.38]) but not SAH (HR, 1.13 [95% CI, 0.99-1.29]; P = .06). Compared with White participants, Black participants had a higher risk of IS (HR, 1.20 [95% CI, 1.09-1.33]) and ICH (HR, 1.67 [95% CI, 1.30-2.13]) and Hispanic participants of any race had a higher risk of SAH (HR, 3.81 [95% CI, 1.29-11.22]). There was no consistent evidence that race and ethnicity modified the association of cumulative mean SBP with first incident stroke and stroke type. Conclusions and Relevance: The findings of this cohort study suggest that cumulative mean SBP was associated with incident stroke type, but the associations did not differ by race and ethnicity. Culturally informed stroke prevention programs should address modifiable risk factors such as SBP along with social determinants of health and structural inequities in society.

Constructing synthetic datasets with generative artificial intelligence to train large language models to classify acute renal failure from clinical notes.

OBJECTIVES: To compare performances of a classifier that leverages language models when trained on synthetic versus authentic clinical notes. MATERIALS AND METHODS: A classifier using language models was developed to identify acute renal failure. Four types of training data were compared: (1) notes from MIMIC-III; and (2, 3, and 4) synthetic notes generated by ChatGPT of varied text lengths of 15 (GPT-15 sentences), 30 (GPT-30 sentences), and 45 (GPT-45 sentences) sentences, respectively. The area under the receiver operating characteristics curve (AUC) was calculated from a test set from MIMIC-III. RESULTS: With RoBERTa, the AUCs were 0.84, 0.80, 0.84, and 0.76 for the MIMIC-III, GPT-15, GPT-30- and GPT-45 sentences training sets, respectively. DISCUSSION: Training language models to detect acute renal failure from clinical notes resulted in similar performances when using synthetic versus authentic training data. CONCLUSION: The use of training data derived from protected health information may not be needed.

An Interdisciplinary, Comprehensive Recovery Pathway Improves Microsurgical Breast Reconstruction Delivery.

INTRODUCTION: Free-flap (autologous) breast reconstruction demonstrates superiority over alloplastic approaches but is offered infrequently. Enhanced recovery protocols can address postoperative challenges, but most literature is limited to inpatient interventions and outcomes. This study describes an adoptable, longitudinally comprehensive and multidisciplinary recovery pathway for autologous reconstruction which adds to the current guidelines. The authors aimed to allow perioperative outcomes comparable to alloplastic reconstructions. METHODS: All autologous Comprehensive Recovery Pathway (CRP) subjects from a single surgeon were retrospectively included. A comparator group of equal size was randomly selected from institutional subpectoral and dual-plane tissue expander patients having Enhanced Recovery After Surgery guideline-directed care. All subjects in both cohorts received preoperative paravertebral regional blocks. Operative detail, inpatient recovery, longitudinal morphine equivalents (MEs) required, and complications were compared. RESULTS: Each cohort included 71 cases (99 breasts). Despite longer operations, intraoperative MEs were fewer in autologous cases ( P = 0.02). Morphine equivalents during inpatient stay were similar between cohorts, with both being discharged on median day 2. Multivariate regression demonstrated a 0.8-day increased stay for autologous subjects with additional contribution from bilateral cases, body mass index, and age ( P < 0.05). Autologous subjects were regularly discharged postoperative day 1 (17%) and postoperative day 2 (39%), with trend toward earlier discharge ( P < 0.01). Outpatient MEs were significantly fewer in autologous subjects, corresponding to a 30- to 150-mg oxycodone difference ( P < 0.01). Major complication occurred in 12.7% of autologous and 22.5% of alloplastic subjects ( P = 0.11). Flap loss occurred in 1 autologous subject versus 11 alloplastic failures ( P < 0.01). CONCLUSIONS: This study details partnership between the plastic surgery service, regional and acute pain anesthesia services, and dedicated nursing with longitudinal optimizations allowing perioperative outcomes improved over current literature. Patients in the CRP used fewer opioids from operation through follow-up with comparable length of stay and significantly fewer reconstructive failures than alloplastic subjects. The pathway may be quickly adopted into academic practice patterns and mitigates traditional barriers, allowing extension of autologous reconstruction offerings.

Effects of wind-driven current and thermal dynamics in a temperate monomictic reservoir: Implications for manganese transport and treatment in water supply systems.

Increasing manganese (Mn) concentrations in source water contribute to aesthetic and health-related concerns in drinking water. The challenges with Mn in drinking water primarily arise from elevated Mn concentrations in the water supply reservoir, with the inefficacy of Mn treatment largely attributed to fluctuating Mn levels in the water source. A three-dimensional Mn cycle model in a temperate monomictic reservoir, Tarago Reservoir, and a decision support system reflecting Mn variations in the local water treatment plant have been established in previous research. This study aimed to examine Mn variations from the reservoir to raw water and treated water under the influence of wind conditions during different stages of thermal structure, and discover valuable recommendations for Mn treatment in the local water supply system. We crafted 12 scenarios to scrutinize the impact of varying intensities of offshore and onshore winds on hydrodynamic processes and Mn transport during strong thermal stratification, weak thermal stratification, and turnover. The scenario analysis revealed that, during the gradual weakening of thermal stratification, offshore wind induced a substantial amount of Mn to the upper layers near the water intake point. Conversely, onshore wind hindered the upward transport of Mn. The simulated Mn in the raw water under the 12 scenarios indicated that the timing of turnover in the Tarago Reservoir is the primary concern for Mn treatment in the water treatment plant. Additionally, close attention should be given to the frequency and intensity of offshore winds during the weakening of thermal stratification.

Development of a predictive model for risk stratification of acute kidney injury in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Acute kidney injury (AKI) following hyperthermic intraperitoneal chemotherapy (HIPEC) is common. Identifying patients at risk could have implications for surgical and anesthetic management. We aimed to develop a predictive model that could predict AKI based on patients' preoperative characteristics and intraperitoneal chemotherapy regimen. We retrospectively gathered data of adult patients undergoing HIPEC at our health system between November 2013 and April 2022. Next, we developed a model predicting postoperative AKI using multivariable logistic regression and calculated the performance of the model (area under the receiver operating characteristics curve [AUC]) via tenfold cross-validation. A total of 412 patients were included, of which 36 (8.7%) developed postoperative AKI. Based on our multivariable logistic regression model, multiple preoperative and intraoperative characteristics were associated with AKI. We included the total intraoperative cisplatin dose, body mass index, male sex, and preoperative hemoglobin level in the final model. The mean area under the receiver operating characteristics curve value was 0.82 (95% confidence interval 0.71-0.93). Our risk model predicted AKI with high accuracy in patients undergoing HIPEC in our institution. The external validity of our model should now be tested in independent and prospective patient cohorts.