Comparing prospectively assigned trial and real-world lung cancer patients.

Aim: To evaluate the comparability of a probable clinical trial (CT) cohort derived from electronic medical records (EMR) data with a real-world cohort treated with the same therapy and identified using the same inclusion and exclusion criteria to emulate an external control. Methods: We utilized de-identified patient-level structured data sourced from EMRs. We then compared patterns of overall survival (OS) between probable CT patients with those drawn from non-contemporaneous real-world data (RWD) using a two-sided log-rank test, hazard ratios (HRs) using a Cox proportional-hazards model and Kaplan-Meier (KM) survival curves. Each regression estimate was calculated with a corresponding 95% confidence interval. We additionally conducted multiple matching methods to assess their relative performance. Results: Median (standard deviation) OS was 10.2 (0.7) months for the RWD arm and 11.3 (1.3) for the probable CT arm with a Log rank p-value equal to 0.4771. OS in both cohorts is longer than the reported CT median OS of 9.2 (0.6). The HRs generated under all five assessed matching methods (including without adjustment) were not statistically significant at the 95% confidence level. Conclusion: Our results suggest, with caveats noted, that survival patterns between real-world and CT cohorts in this NSCLC setting are not statistically significantly different.

Nystagmus Characteristics in Albinism: Unveiling the Link to Foveal Hypoplasia and Visual Acuity.

Purpose: The purpose of this study was to describe the association among nystagmus characteristics, foveal hypoplasia, and visual acuity in patients with albinism. Methods: We studied nystagmus recordings of 50 patients with albinism. The nystagmus waveform was decomposed into two types: dominantly pendular and dominantly jerk. We correlated the nystagmus type, amplitude, frequency, and percentage of low velocity (PLOV) to Snellen visual acuity and foveal hypoplasia grades. Results: The grade of foveal hypoplasia and visual acuity showed a strong correlation (r = 0.87, P < 0.0001). Nystagmus type and PLOV had the strongest significant (P < 0.0001) correlation with visual acuity (r = 0.70 and r = -0.56, respectively) and with foveal hypoplasia (r = 0.76 and r = -0.60, respectively). Patients with pendular nystagmus type had the lowest PLOV, and the highest grade of foveal hypoplasia (P < 0.0001). Severe foveal hypoplasia (grade 4), was almost invariably associated with pendular nystagmus (86%). Conclusions: Foveal hypoplasia grade 4 is associated with pendular nystagmus, lower PLOV, and worse visual acuity. Based on these results, nystagmus recordings at a young age may contribute to predicting visual outcomes.

Improving Real-World Mortality Data Quality in Oncology Research: Augmenting Electronic Medical Records With Obituary, Social Security Death Index, and Commercial Claims Data.

PURPOSE: This study evaluated the relative improvements in mortality data capture of adding different external data to enriched electronic medical records (EMRs) for patients with melanoma. METHODS: An enriched EMR database, containing structured and unstructured data, was used to evaluate the incremental mortality data capture of the following external data sources: Social Security Administration (SSA), public obituary, and an administrative open-claims database for the claims data set. Overall survival (OS) was assessed for each data set and the composite data set using the Kaplan-Meier method. RESULTS: A total of 3,882 patients were included in the study. The enriched EMR data set identified 1,085 patients with a death record. The SSA data set identified 213 patients (73 unique when combined with enriched EMR) with a death record, while the obituary data set identified 1,127 patients (241 unique). The administrative claims data set identified 378 patients (73 unique) with a death record; however, all these unique patients were already accounted for in the combined SSA and obituary data set. The composite data set yielded a median OS of 13.39 years, about 4 years shorter than the enriched EMR data set alone (17.63 years). CONCLUSION: When the enriched EMR data set was augmented with one external data set, the obituary data set provided the most additional value, followed by claims, and then SSA. The augmentation of all the data sources had a significant impact on the OS results compared with enriched EMR alone.

Nutritional composition and consumer acceptance of tomato paste fortified with palm weevil larvae (Rhynchophorus phoenicis Fabricius) in the Ashanti region, Ghana.

Edible insects, such as palm weevil larvae, have been promoted as an alternative source of nutrients in developing countries for their nutritional benefits, cost-effective rearing, and yearly availability. Unfortunately, consumer acceptance remains a barrier to their utilization. A supplemental palm weevil larvae and tomato paste were developed as part of efforts to understand whether incorporating edible insects into staple foods could help overcome this barrier. Palm weevil larvae flour and tomato paste were mixed in three formulations that had 8, 15, and 30% of palm weevil larvae flour. Samples were subjected to proximate and mineral content analyses and sensory evaluation. Among the blends, tomato paste containing 30% palm weevil larvae had the highest protein, fat, and total solids content as compared to unfortified tomato paste. Iron and zinc levels also increased with increasing levels of palm weevil larvae flour. Carbohydrate and crude fiber concentrations of the samples, however, decreased with increasing fortification levels. The overall acceptance and willingness to purchase fortified tomato paste as determined by sensory evaluation was high for all samples and increased with increasing knowledge about palm weevil larvae's nutritional benefits. Overall acceptance and willingness to purchase fortified tomato paste were significantly dependent on the samples' color and consumers' overall liking of the products. Tomato paste fortified with palm weevil larvae can provide a complementary source of iron for Ghanaians.

Evidence for a Multimodal Pain Management Regimen in Reduction of Postoperative Opioid Use in Pediatric Patients Receiving Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: This project aims to evaluate the relationship between increased use of intraoperative nonopioid analgesics, muscle relaxers, and anesthetics and postoperative outcomes, including opioid utilization, time until ambulation, and hospital length of stay. SUMMARY OF BACKGROUND DATA: Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine that occurs in otherwise healthy adolescents, occurring with a frequency of 1% to 3%. Up to 60% of patients receiving spinal surgeries, particularly posterior spinal fusion (PSF), experience at least 1 day of moderate-to-severe pain after surgery. PATIENTS AND METHODS: This is a retrospective chart review of pediatric patients aged 10 to 17 having received PSF with >5 levels fused for AIS at a dedicated children's hospital and a regional tertiary referral center with a dedicated pediatric spine program between January 2018 and September 2022. A linear regression model was used to evaluate the influence of baseline characteristics and intraoperative medications on the total amount of postoperative morphine milligram equivalents received. RESULTS: There were no significant differences in the background characteristics of the two patient populations. Patients receiving PSF at the tertiary referral center received equivalent or greater amounts of all nonopioid pain medications and demonstrated decreased time until ambulation (19.3 vs . 22.3 h), postoperative opioid use (56.1 vs . 70.1 MME), and postoperative hospital length of stay (35.9 vs . 58.3 h). Hospital location was not individually associated with a difference in postoperative opioid use. There was not a significant difference in postoperative pain ratings. When accounting for all other variables, liposomal bupivacaine had the greatest contribution to the decrease in postoperative opioid use. CONCLUSION: Patients receiving greater amounts of nonopioid intraoperative medications utilized 20% fewer postoperative morphine milligram equivalents, were discharged 22.3 hours earlier and had earlier recorded evidence of mobility. Postoperatively, nonopioid analgesics were as effective as opioids in the reduction of subjective pain ratings. This study further demonstrates the efficacy of multimodal pain management regimens in pediatric patients receiving PSF for AIS.

Characteristics of substance-addicted mothers that predict graduation from the family treatment court.

INTRODUCTION: In the United States, substance addiction is a major contributing factor to incarceration of mothers and separation of children from their families. Five hundred Family Treatment Courts (FTC) operate across the country to combat the growing problem of women addicted to drugs. The FTC model provides mothers with substance addiction treatment, intensive judicial monitoring, repeated drug testing, counseling, incentives or sanctions, and case management with the goal of reaching long-term sobriety and reunification with their children. DESIGN: This retrospective study examined the relationship between sociodemographic characteristics and substance use characteristics, in predicting participants' graduations from the FTC program. METHODS: Data were gathered from 317 participants from five Family Treatment Courts in the southeastern United States and analyzed using logistic regression. RESULTS: Participants who completed the FTC program were more likely to be older, completed Cognitive Behavioral Training, completed high school, and Caucasian. CONCLUSION: Age and completion of Cognitive Behavioral Therapy were the greatest predictors of graduating from the Family Treatment Court. These results convey the need for development of interventions tailored to each participant's age to maximize the success of the FTC participants. In addition, Cognitive Behavioral Therapy should be integrated into all FTC programs. CLINICAL RELEVANCE: The findings from this study will offer research scholars a foundation for designing future studies, aid researchers in creating interventions to increase success in substance addiction treatment programs, and contribute to the framework for theory development. In addition, understanding characteristics that may influence graduation from the Family Treatment Court will provide valuable information on developing interventions to support participants' success.

Knowledge of immediate newborn care and management of complications among midwives in Ghana.

OBJECTIVE: Midwives are instrumental in improving maternal/newborn health outcomes. Since complications after childbirth are leading causes of maternal deaths, midwives' knowledge of how to manage complications and care for the newborn is important. This study assessed midwives' knowledge of immediate newborn care and management of postpartum complications. DESIGN: A cross-sectional descriptive survey design was used. SETTING: Four hospitals that provide inpatient maternity services in Tamale, Ghana. PARTICIPANTS: 245 midwives who worked in the four hospitals. MEASUREMENTS: Data were collected in December 2018 using an electronic survey questionnaire by the Johns Hopkins Program for International Education in Gynecology and Obstetrics, and analyzed using descriptive, bivariate, and multivariate statistics. FINDINGS: About 98% of midwives were female. The mean age of midwives was 31.87 years. The percentage of midwives who responded correctly to questions on newborn care and management of postpartum complications ranged from 29.80% to 89.39%, and 32.17% to 91.43% respectively. Midwives were most knowledgeable about breastfeeding and immediate hemorrhage intervention, and least knowledgeable about cord care, thermal protection, newborn resuscitation, contraindications for vacuum extraction, treating metritis, and performing a cervical repair. Years of experience and age are predictive factors of midwives' knowledge. CONCLUSION/IMPLICATIONS: There remains the opportunity for continuing education on complication management. Additional training of midwives on newborn resuscitation is recommended.

A Longitudinal Study Identifying the Characteristics and Content Knowledge of Those Seeking Certification to Teach Secondary Biology in the United States.

Teacher content knowledge has been identified as a key prerequisite to effective instruction, and current educational policies require measurement of teacher content knowledge to assess candidacy for licensure. The primary instruments used in the United States are the Praxis Subject Assessment exams, which are designed to measure the subject-specific content knowledge needed to be a teacher. The Praxis Biology Subject Assessment exam, used by 42 U.S. states in the past decade, is the most common national measure used to determine biology content knowledge for teacher certification. Demographic and performance data from examinees (N = 43,798) who took the Praxis Biology Subject Assessment from 2006 to 2015 were compared to present a much-needed picture of who is seeking certification to teach biology, how different groups of aspiring biology teachers have performed, and how demographic makeup of prospective biology teachers compares with reports in previous studies describing the composition of the biology teacher workforce. Results indicate the majority of students self-reported as White (76%), female (66%), having undergraduate grade point averages (GPAs) at or above a 3.0 (76%) and majoring in biology (45%). Additionally, the demographic data were included in a linear regression model to determine the factors that explained the most variance in performance of the examinee. The model revealed substantial differences in average performance and pass rates between examinees of different genders, races, undergraduate majors, undergraduate GPAs, and census regions. This suggests that if the examinee is a White science, technology, engineering, and mathematics major, man with a 3.5 or higher undergraduate GPA, resides in the western United States, or plans to teach in a suburban school, the examinee will on average outperform their counterparts on the exam. From our analyses, we suggest several measures for the improvement of the biology teaching workforce and establish potential issues in the teacher pipeline that may impact the quality and diversity of U.S. biology teachers.

Effects of Individual Amino Acids on PPARα Transactivation, mTORC1 Activation, ApoA-I Transcription and pro-ApoA-I Secretion.

A higher concentration of apolipoprotein A-I (ApoA-I) is associated with increased high density lipoprotein functionality and reverse cholesterol transport (RCT). A promising strategy to prevent cardiovascular diseases is therefore to improve RCT by increasing de novo ApoA-I production. Since experimental animal models have suggested effects of amino acids on hepatic lipoprotein metabolism, we here examined the effects of different amino acids on hepatic ApoA-I production. Human hepatocytes (HepG2) were exposed to six individual amino acids for 48 h. ApoA-I transcription and secreted pro-ApoA-I protein concentrations were analyzed using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assays (ELISA), respectively. Additionally, CPT1 and KEAP1 mRNA expression, peroxisome proliferator-activated receptor alpha (PPARα) transactivation, and mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation were determined. Leucine, glutamic acid, and tryptophan increased ApoA-I and CPT1 mRNA expression. Tryptophan also strongly increased PPARα transactivation. Glutamine, proline, and histidine increased pro-ApoA-I protein concentrations but mTORC1 phosphorylation remained unchanged regardless of the amino acid provided. In conclusion, individual amino acids have different effects on ApoA-I mRNA expression and pro-ApoA-I production which can partially be explained by specific effects on PPARα transactivation, while mTORC1 phosphorylation remained unaffected.

CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials.

PURPOSE: To investigate the natural disease course of retinal dystrophies associated with crumbs cell polarity complex component 1 (CRB1) and identify clinical end points for future clinical trials. DESIGN: Single-center, prospective case series. METHODS: An investigator-initiated nationwide collaborative study that included 22 patients with CRB1-associated retinal dystrophies. Patients underwent ophthalmic assessment at baseline and 2 years after baseline. Clinical examination included best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography, full-field stimulus threshold (FST), fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence imaging. RESULTS: Based on genetic, clinical, and electrophysiological data, patients were diagnosed with retinitis pigmentosa (19 [86%]), cone-rod dystrophy (2 [9%]), or isolated macular dystrophy (1 [5%]). Analysis of the entire cohort at 2 years showed no significant changes in BCVA (P = .069) or V4e isopter seeing retinal areas (P = .616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at the 2-year follow-up (P < .001). FST responses were measurable in patients with nonrecordable electroretinograms. On average, FST responses remained stable during follow-up. CONCLUSION: In CRB1-associated retinal dystrophies, visual acuity and visual field measures remain relatively stable over the course of 2 years. Microperimetry showed a significant decrease in retinal sensitivity during follow-up and may be a more sensitive progression marker. Retinal sensitivity on microperimetry may serve as a functional clinical end point in future human treatment trials for CRB1-associated retinal dystrophies.

Predictors of adverse birth outcomes among pregnant adolescents in Ashanti Region, Ghana.

Adolescent pregnancy is associated with adverse birth outcomes. However, the determinants of these outcomes are understudied. The present study sought to identify the predictors of adverse birth outcomes among pregnant adolescents in Ghana. In this prospective health centre-based study, 416 pregnant adolescents, aged 13-19 years old, were followed, and 270 birth outcomes were evaluated. We collected data on socio-demographic variables, eating behaviour, household hunger scale (HHS), lived poverty index (LPI) and compliance to antenatal interventions. The prevalence of low birth weight (LBW) and preterm births (PTB) were 15⋅2 and 12⋅5 %, respectively. Pregnant adolescents with no formal education (AOR 9⋅0; P = 0⋅004; 95 % CI 2⋅1, 39⋅8), those who experienced illness (AOR 3⋅0; P = 0⋅011; 95 % CI 1⋅3, 7⋅0), those who experienced hunger (OR 2⋅9; P = 0⋅010; 95 % CI 1⋅3, 6⋅5) and those with high LPI (OR 2⋅5; P = 0⋅014; 95 % CI 1⋅2, 5⋅3) presented increased odds of delivering preterm babies compared with those who have had secondary education, did not experience any illness, were not hungry or having low LPI, respectively. Pregnant adolescents who used insecticide-treated net (ITN) (AOR 0⋅4; P = 0⋅013; 95 % CI 0⋅2, 0⋅9) presented reduced odds LBW children; while those who experienced illness (AOR 2⋅7; P = 0⋅020; 95 % CI 1⋅2, 6⋅0), poorer pregnant adolescents (OR 2⋅5; P = 0⋅014; 95 % CI 1⋅1, 4⋅8) and those who experienced hunger (AOR 3⋅0; P = 0⋅028; 95 % CI 1⋅1, 8⋅1) presented increased odds of LBW children compared with those who used ITN, were not ill, were not poor or did not experience hunger. Adverse birth outcomes were associated with ANC compliance and socioeconomic factors of the pregnant adolescents. Hence, strengthening antenatal uptake and compliance by pregnant adolescents, promoting their livelihood and socioeconomic status, and interventions to prevent teenage pregnancies are strongly recommended.

Potential Contribution of Short Chain Fatty Acids to Hepatic Apolipoprotein A-I Production.

Apolipoprotein A-I (ApoA-I) is the major protein of high density lipoprotein (HDL) particles and has a crucial role in reverse cholesterol transport (RCT). It has been postulated that elevating production of de novo ApoA-I might translate into the formation of new functional HDL particles that could lower cardiovascular disease (CVD) risk via RCT. During inflammation, serum ApoA-I concentrations are reduced, which contributes to the development of dysfunctional HDL particles as Serum Amyloid A (SAA) overtakes the position of ApoA-I within the HDL particles. Therefore, instead of elevating serum HDL cholesterol concentrations, rescuing lower serum ApoA-I concentrations could be beneficial in both normal and inflamed conditions. Several nutritional compounds, amongst others short chain fatty acids (SCFAs), have shown their capacity to modulate hepatic lipoprotein metabolism. In this review we provide an overview of HDL and more specific ApoA-I metabolism, SCFAs physiology and the current knowledge regarding the influence of SCFAs on ApoA-I expression and synthesis in human liver cells. We conclude that the current evidence regarding the effect of SCFAs on ApoA-I transcription and secretion is promising, however there is a need to investigate which dietary fibres could lead to increased SCFAs formation and consequent elevated ApoA-I concentrations.

Beyond nephronophthisis: Retinal dystrophy in the absence of kidney dysfunction in childhood expands the clinical spectrum of CEP83 deficiency.

The CEP83 protein is an essential part in the first steps of ciliogenesis, causing a ciliopathy if deficient. As a core component of the distal appendages of the centriole, CEP83 is located in almost all cell types and is involved in the primary cilium assembly. Previously reported CEP83 deficient patients all presented with nephronophthisis and kidney dysfunction. Despite retinal degeneration being a common feature in ciliopathies, only one patient also had retinitis. Here, we present two unrelated patients, who both presented with retinitis pigmentosa, without nephronophthisis or any form of kidney dysfunction. Both patients harbor bi-allelic variants in CEP83. This report expands the current clinical spectrum of CEP83 deficiency. For timely diagnosis of CEP83 deficiency, we advocate that CEP83 should be included in gene panels for inherited retinal diseases.

Factors associated with iron deficiency anaemia among pregnant teenagers in Ashanti Region, Ghana: A hospital-based prospective cohort study.

BACKGROUND: Iron Deficiency Anaemia (IDA) is reportedly high in pregnant adults and the causes well studied. However, among pregnant teenagers, the levels and associated factors of IDA are not fully understood. METHODS: In a prospective cohort study among Ghanaian pregnant teenagers, aged 13-19 years, IDA prevalence and associated factors were investigated. Sociodemographic data, household hunger scale (HHS), lived poverty index (LPI), FAO's women's dietary diversity score (WDDS) and interventions received during antenatal care (ANC) were obtained from 416 pregnant teenagers in Ashanti Region, Ghana. Micronutrient intakes using a repeated 24-hour dietary recall, and mid-upper arm circumference (MUAC) were determined and blood samples analysed for haemoglobin (Hb), serum levels of ferritin, prealbumin, vitamin A, total antioxidant capacity (TAC), C-reactive protein (CRP), and zinc protoporphyrin (ZPP). RESULTS: Anaemia (Hb cutoff <11.0 g/dL) was 57.1%; deficient systemic supply of iron stores (31.4%), depleted body stores of iron (4.4%), inadequate dietary iron intake (94.5%), and inadequate multiple micronutrient intakes (49.5%), were all notable among study participants. Between-subject effects using Generalized Linear Modelling indicated malaria tablet given at ANC (p = 0.035), MUAC (p = 0.043), ZPP (p<0.001), ZPP/Hb ratio (p<0.001) and depleted body iron stores (DBIS) (p<0.001) to significantly affect Hb levels. Pregnant teenagers with a high ZPP/Hb ratio (OR = 9.7, p<0.001, 95%CI = 6.0-15.8) had increased odds of being anaemic compared to those with normal ZPP/Hb ratio. Participants who were wasted (OR = 1.2, p = 0.543, 95%CI = 0.6-2.3), and those with depleted iron stores (OR = 3.0, p = 0.167, 95%CI = 0.6-14.6) had increased odds of being anaemic. Participants who experienced hunger were close to 3 times more likely (OR = 2.9, p = 0.040, 95%CI = 1.1-7.8) for depleted iron stores, compared to those who did not experience hunger. Also, participants with inadequate multiple micronutrients intakes (OR = 2.6, p = 0.102, 95%CI = 0.8-8.4), and those with low serum levels of ferritin (OR = 3.3, p = 0.291, 95%CI = 0.4-29.2) had increased odds of depleted body iron stores. CONCLUSIONS: IDA is common among pregnant teenagers and the related factors include malaria tablets given at ANC, maternal hunger, maternal MUAC, a deficient systemic supply of iron, depleted body iron stores, ZPP, and ZPP/Hb ratio. Appropriate interventions are urgently needed to address the causes of IDA among pregnant teenagers.

Characterizing managing physicians by claims sequences in episodes of care.

Value-based healthcare in the US is a payment structure that ties reimbursement to quality rather than volume alone. One model of value-based care is the Tennessee Division of TennCare's Episodes of Care program, which groups common health conditions into episodes using specified time windows, medical code sets and quality metrics as defined in each episode's Detailed Business Requirements [1,2]. Tennessee's program assigns responsibility for an episode to a managing physician, presenting a unique opportunity to study physician variability in cost and quality within these structured episodes. This paper proposes a pipeline for analysis demonstrated using a cohort of 599 Outpatient and Non-Acute Inpatient Cholecystectomy episodes managed by BlueCross BlueShield of Tennessee in 2016. We sorted episode claims by date of service, then calculated the pairwise Levenshtein distance between all episodes. Next, we adjusted the resulting matrix by cost dissimilarity and performed agglomerative clustering. We then examined the lowest and highest average episode cost clusters for patterns in cost and quality. Our results indicate that the facility type where the surgery takes place is important: outpatient ambulatory care center for the lowest cost cluster, and hospital operating room for the highest cost cluster. Average patient risk scores were higher in the highest cost cluster than the lowest cost cluster. Readmission rate (a quality metric tied to managing physician performance) was low for the whole cohort. Lastly, we explain how our analytical pipeline can be generalized and extended to domains beyond Episodes of Care.

Defining inclusion criteria and endpoints for clinical trials: a prospective cross-sectional study in CRB1-associated retinal dystrophies.

PURPOSE: To investigate the retinal structure and function in patients with CRB1-associated retinal dystrophies (RD) and to explore potential clinical endpoints. METHODS: In this prospective cross-sectional study, 22 patients with genetically confirmed CRB1-RD (aged 6-74 years), and who had a decimal best-corrected visual acuity (BCVA) ≥ 0.05 at the last visit, were studied clinically with ETDRS BCVA, corneal topography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, Goldmann visual field (VF), microperimetry, full-field electroretinography (ERG) and full-field stimulus testing (FST). Ten patients were from a genetic isolate (GI). RESULTS: Patients had retinitis pigmentosa (n = 19; GI and non-GI), cone-rod dystrophy (n = 2; GI) or macular dystrophy (n = 1; non-GI). Median age at first symptom onset was 3 years (range 0.8-49). Median decimal BCVA in the better and worse-seeing eye was 0.18 (range 0.05-0.83) and 0.08 (range light perception-0.72), respectively. Spectral-domain optical coherence tomography (SD-OCT) showed cystoid maculopathy in 8 subjects; inner retinal thickening (n = 20), a well-preserved (para)foveal outer retina (n = 7) or severe (para)foveal outer retinal atrophy (n = 14). All retinal layers were discernible in 13/21 patients (62%), with mild to moderate laminar disorganization in the others. Nanophthalmos was observed in 8 patients (36%). Full-field stimulus testing (FST) provided a subjective outcome measure for retinal sensitivity in eyes with (nearly) extinguished ERG amplitudes. CONCLUSIONS: Despite the generally severe course of CRB1-RDs, symptom onset and central visual function are variable, even at advanced ages. Phenotypes may vary within the same family. Imaging and functional studies in a prospective longitudinal setting should clarify which endpoints may be most appropriate in a clinical trial.

Butyric Acid Added Apically to Intestinal Caco-2 Cells Elevates Hepatic ApoA-I Transcription and Rescues Lower ApoA-I Expression in Inflamed HepG2 Cells Co-Cultured in the Basolateral Compartment.

Apolipoprotein A-I (ApoA-I) concentrations are decreased during inflammation, which may reduce high-density lipoprotein (HDL) functionality. Thus, rescuing ApoA-I concentrations during inflammation might help to prevent atherosclerosis. Recent studies have shown that butyric acid (C4) has anti-inflammatory effects and rescues ApoA-I production. However, whether intestinal short chain fatty acids (SCFAs) are able to influence hepatic processes is unknown. Therefore, we investigated C4 anti-inflammatory effects on ApoA-I transcription in the intestine-liver co-culture model. C4 dose-response experiments in the presence or absence of cytokines were performed in a co-culture system including Caco-2 cells, HepG2 cells, or both. Changes in ApoA-I transcription in Caco-2 cells and HepG2 cells were analyzed using qPCR. C4 increased ApoA-I expression in HepG2 cells that cultured alone. When both cells were cultured together, C4 decreased ApoA-I expression in Caco-2 cells and increased ApoA-I expression in HepG2 cells. However, adding C4 to apical Caco-2 cells resulted in a smaller effect in HepG2 cells compared with adding C4 directly to the hepatocytes. Moreover, C4 rescued ApoA-I expression in inflamed HepG2 cells. These findings suggests that intestinal SCFAs can affect hepatic processes. However, the smaller effect in the co-culture experiment indicates cross-talk between intestine and liver.

Vasopressors and Inotropes as Predictors of Mortality in Acute Severe Cardiogenic Shock Treated With the Impella Device.

BACKGROUND: Vasopressors and inotropes are the primary pharmacologic agents in the management of cardiogenic shock. Increased use of these agents in the setting of cardiogenic shock treated with the Impella is associated with increased mortality. This study evaluates the use of vasopressors and inotropes as predictors of mortality in patients treated with the Impella for acute cardiogenic shock. METHODS: This retrospective study included 276 patients treated with the Impella 2.5, Impella CP, or Impella 5.0 from March 2011 to January 2020 at a single, tertiary referral center for acute cardiogenic shock. RESULTS: All-cause in-hospital mortality was 44.6%. Mortality significantly increased with escalating use of vasopressors and inotropes, with the most significant increase in mortality from use of 2 agents to the use of 3 agents (8.1% vs 39.7%, p < 0.001). There was no difference in mortality whether dobutamine or milrinone was used (44.4% vs 35.7%, p = 0.41); there was increased mortality with use of multiple inotropes. Patients treated with only vasopressors had increased mortality compared to those treated with a combination of agents that included 1 inotrope. CONCLUSIONS: The escalating need for vasopressors and inotropes and particular combinations of these agents are significant predictors of mortality that may help determine whether the Impella or higher level of support is more appropriate to treat acute cardiogenic shock.