Corrigendum: Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles.

[This corrects the article DOI: 10.3389/fnana.2024.1385932.].

Freeform robotic optical coherence tomography beyond the optical field-of-view limit.

Imaging complex, non-planar anatomies with optical coherence tomography (OCT) is limited by the optical field of view (FOV) in a single volumetric acquisition. Combining linear mechanical translation with OCT extends the FOV but suffers from inflexibility in imaging non-planar anatomies. We report the freeform robotic OCT to fill this gap. To address challenges in volumetric reconstruction associated with the robotic movement accuracy being two orders of magnitudes worse than OCT imaging resolution, we developed a volumetric registration algorithm based on simultaneous localization and mapping (SLAM) to overcome this limitation. We imaged the entire aqueous humor outflow pathway, whose imaging has the potential to customize glaucoma surgeries but is typically constrained by the FOV, circumferentially in mice as a test. We acquired volumetric OCT data at different robotic poses and reconstructed the entire anterior segment of the eye. The reconstructed volumes showed heterogeneous Schlemm's canal (SC) morphology in the reconstructed anterior segment and revealed a segmental nature in the circumferential distribution of collector channels (CC) with spatial features as small as a few micrometers.

On alert for Ebola: public health risk assessment of travellers from Uganda to the USA during the 2022 outbreak.

BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.

Fetal dose assessment in a pregnant patient with brain tumor: A comparative study of proton PBS and 3DCRT/VMAT radiation therapy techniques.

PURPOSE: The treatment of brain tumors in pregnant patients poses challenges, as the out-of-field dose exposure to the fetus can potentially be harmful. A pregnant patient with prior radiation treatment was presented with a brain tumor at our clinic. This work reports on our pre-treatment study that compared fetal dose exposure between intensity-modulated proton therapy (IMPT) using pencil beam scanning (PBS) and conventional photon 3D conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT), and the subsequent pregnant patient's radiation treatment. MATERIALS AND METHODS: Pre-treatment measurements of clinical plans, 3DCRT, VMAT, and IMPT, were conducted on a phantom. Measurements were performed using a device capable of neutron detections, closely following AAPM guidelines, TG158. For photon measurements, fetus shielding was utilized. On patient treatment days, which was determined to be proton treatment, shielding was used only during daily imaging for patient setup. Additionally, an in vivo measurement was conducted on the patient. RESULTS: Measurements showed that IMPT delivered the lowest fetal dose, considering both photon and neutron out-of-field doses to the fetus, even when shielding was implemented for photon measurements. Additionally, the proton plans demonstrated superior treatment for the mother, a reirradiation case. CONCLUSION: The patient was treated with proton therapy, and the baby was subsequently delivered at full term with no complications. This case study supports previous clinical findings and advocates for the expanded use of proton therapy in this patient population.

The impact of the titanium cranial hardware in proton single-field uniform dose plans.

BACKGROUND: Neurosurgical cranial titanium mesh and screws are commonly encountered in postoperative radiation therapy. However, only a limited number of reports are available in the context of proton therapy, resulting in a lack of consensus among the proton centers regarding the protocol for handling the hardware. PURPOSE: This study is to examine the impact of the hardware in proton plans. The results serve as evidence for proton centers to generate standard operating procedures to manage the hardware in proton treatment. METHODS: Plans with different gantry angles and material overrides are generated on the CT images of a phantom made of the hardware. The dose distributions of the plans with and without material override, at different depths are compared. Films and ionization chambers are used to measure the plans and the measurements are compared to the treatment planning system (TPS) calculations by gamma analysis. RESULTS: There are some overdose and underdose regions downstream of the hardware. The overdose and underdose values are within a few percent of the prescribed dose when multiple fields with large hinge angles are used. The gamma analysis results show that the measurements agree with the TPS calculations within limits that are clinically relevant. CONCLUSION: The study has demonstrated the influence of the hardware on proton plans. Based on the result of this study, a standard operating procedure of managing the hardware has been implemented in our clinic.

Photoinduced Group Transposition via Iridium-Nitrenoid Leading to Amidative Inner-Sphere Aryl Migration.

We herein report a fundamental mechanistic investigation into photochemical metal-nitrenoid generation and inner-sphere transposition reactivity using organometallic photoprecursors. By designing Cp*Ir(hydroxamate)(Ar) complexes, we induced photo-initiated ligand activation, allowing us to explore the amidative σ(Ir-aryl) migration reactivity. A combination of experimental mechanistic studies, femtosecond transient absorption spectroscopy, and density functional theory (DFT) calculations revealed that the metal-to-ligand charge transfer enables the σ(N-O) cleavage, followed by Ir-acylnitrenoid generation. The final inner-sphere σ(Ir-aryl) group migration results in a net amidative group transposition.

Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN): a Case-Control Observational Study Protocol.

BACKGROUND: Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed fifirst responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal Refux disease (GERD) and Barrett's Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms. METHODS: Our observational case-cohort study will leverage the longitudinally phenotyped Fire Department of New York (FDNY)-WTC exposed cohort to identify Biomarkers of Airway Disease, Barrett's and Underdiagnosed Refux Noninvasively (BAD-BURN). Our study population consists of n = 4,192 individuals from which we have randomly selected a sub-cohort control group (n = 837). We will then recruit subgroups of i. AHR only ii. GERD only iii. BE iv. GERD/BE and AHR overlap or v. No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life. DISCUSSION: Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of Refux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05216133; January 18, 2022.

Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma.

OBJECTIVE: The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT). METHODS: Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/µL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT. RESULTS: Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/µL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5 k/µL, P=0.01) and larger target tumor volume (median 125 vs. 62 cm3, P=0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death (P=0.04); 1-year OS rates were 63% vs 77% (P=0.03). Receipt of photon versus proton-based RT (OR=3.50, P=0.02), higher mean liver dose (OR=1.19, P<0.01), and longer RT duration (OR=1.49, P=0.02) predicted severe lymphopenia. CONCLUSIONS: HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.

Cost-effectiveness of mask mandates on subways to prevent SARS-CoV-2 transmission in the United States.

BACKGROUND: Community-based mask wearing has been shown to reduce the transmission of SARS-CoV-2. However, few studies have conducted an economic evaluation of mask mandates, specifically in public transportation settings. This study evaluated the cost-effectiveness of implementing mask mandates for subway passengers in the United States by evaluating its potential to reduce COVID-19 transmission during subway travel. MATERIALS AND METHODS: We assessed the health impacts and costs of subway mask mandates compared to mask recommendations based on the number of infections that would occur during subway travel in the U.S. Using a combined box and Wells-Riley infection model, we estimated monthly infections, hospitalizations, and deaths averted under a mask mandate scenario as compared to a mask recommendation scenario. The analysis included costs of implementing mask mandates and COVID-19 treatment from a limited societal perspective. The cost-effectiveness (net cost per averted death) of mandates was estimated for three different periods based on dominant SARS-CoV-2 variants: Alpha, Beta, and Gamma (November 2020 to February 2021); Delta (July to October 2021); and early Omicron (January to March 2022). RESULTS: Compared with mask recommendations only, mask mandates were cost-effective across all periods, with costs per averted death less than a threshold of $11.4 million (ranging from cost-saving to $3 million per averted death). Additionally, mask mandates were more cost-effective during the early Omicron period than the other two periods and were cost saving in January 2022. Our findings showed that mandates remained cost-effective when accounting for uncertainties in input parameters (e.g., even if mandates only resulted in small increases in mask usage by subway ridership). CONCLUSIONS: The findings highlight the economic value of mask mandates on subways, particularly during high virus transmissibility periods, during the COVID-19 pandemic. This study may inform stakeholders on mask mandate decisions during future outbreaks of novel viral respiratory diseases.

How Are We Teaching Advocacy? A National Survey of Internal Medicine Residency Program Directors.

BACKGROUND: Although internal medicine (IM) physicians accept public advocacy as a professional responsibility, there is little evidence that IM training programs teach advocacy skills. The prevalence and characteristics of public advocacy curricula in US IM residency programs are unknown. OBJECTIVES: To describe the prevalence and characteristics of curricula in US IM residencies addressing public advocacy for communities and populations; to describe barriers to the provision of such curricula. DESIGN: Nationally representative, web-based, cross-sectional survey of IM residency program directors with membership in an academic professional association. PARTICIPANTS: A total of 276 IM residency program directors (61%) responded between August and December 2022. MAIN MEASUREMENTS: Percentage of US IM residency programs that teach advocacy curricula; characteristics of advocacy curricula; perceptions of barriers to teaching advocacy. KEY RESULTS: More than half of respondents reported that their programs offer no advocacy curricula (148/276, 53.6%). Ninety-five programs (95/276, 34.4%) reported required advocacy curricula; 33 programs (33/276, 12%) provided curricula as elective only. The content, structure, and teaching methods of advocacy curricula in IM programs were heterogeneous; experiential learning in required curricula was low (23/95, 24.2%) compared to that in elective curricula (51/65, 78.5%). The most highly reported barriers to implementing or improving upon advocacy curricula (multiple responses allowed) were lack of faculty expertise in advocacy (200/276, 72%), inadequate faculty time (190/276, 69%), and limited curricular flexibility (148/276, 54%). CONCLUSION: Over half of US IM residency programs offer no formal training in public advocacy skills and many reported lack of faculty expertise in public advocacy as a barrier. These findings suggest many IM residents are not taught how to advocate for communities and populations. Further, less than one-quarter of required curricula in public advocacy involves experiential learning.

County-level political group density, partisan polarization, and individual-level mortality among adults in the United States: A lagged multilevel study.

Objective: To investigate the associations between county-level political group density, partisan polarization, and individual-level mortality from all causes and from coronary heart disease (CHD) in the United States. Methods: Using data from five survey waves (1998-2006) of the General Social Survey-National Death Index dataset and the County Presidential Election Return 2000 dataset, we fit weighted Cox proportional hazards models to estimate the associations between (1) political group density and (2) partisan polarization measured at the county level in 2000 (n = 313 counties) categorized into quartiles with individual-level mortality (n = 14,983 participants) from all causes and CHD, controlling for individual- and county-level factors. Maximum follow-up was from one year after the survey up until 2014. We conducted these analyses using two separate measures based on county-level vote share differences and party affiliation ideological extremes. Results: In the overall sample, we found no evidence of associations between county-level political group density and individual-level mortality from all causes. There was evidence of a 13% higher risk of dying from heart disease in the highest quartile of county-level polarization (hazards ratio, HR = 1.13; 95% CI = 0.74-1.71). We observed heterogeneity of effects based on individual-level political affiliation. Among those identifying as Democrats, residing in counties with high (vs. low) levels of polarization appeared to be protective against mortality, with an associated 18% lower risk of dying from all causes (HR = 0.82, 95% CI = 0.71-0.94). This association was strongest in areas with the highest concentrations of Democrats. Conclusions: Among all study participants, political group density and polarization at the county level in 2000 were not linked to individual-level mortality. At the same time, we found that Democratic party affiliation may be protective against the adverse effects of high polarization, particularly in counties with high concentrations of Democrats. Future research should further explore these associations to potentially identify new structural interventions to address political determinants of population health.

Assessment of immunosuppression induction with basiliximab compared to antithymocyte-globulin in adult heart transplant patients.

BACKGROUND: Patients undergoing heart transplants are at risk of rejection which can have significant morbidity and mortality. Induction immunosuppression at the time of transplant reduces the early risk and has additional benefits. The induction agent of choice within our program was changed from rabbit antithymocyte-globulin (rATG) to basiliximab, so it was necessary to evaluate whether this had any impact on patient outcomes. OBJECTIVES: Our primary objective was to describe rejection, infection, and other outcomes in adult heart transplant patients at the University of Alberta Hospital in Edmonton, Canada. METHODS: This study was a nonrandomized, retrospective cohort study. RESULTS: Sixty-three patients were included with median ages 50 years versus 54 years. More female patients received rATG (20% vs. 42.4%). The most common indication for transplant in both cohorts was ICM (63.3% vs. 57.6%). Patients who received rATG had significantly higher PRA (0% vs. 43%, p < .001). Acute rejection episodes were similar between basiliximab and rATG at 3 months (16.7% vs. 15.1%; p = 1.0) and 6-months (30.0% vs. 18.1%; p = .376). Infections were not statistically different with basiliximab compared to rATG at 3-months, 43.3% vs. 63.6% and at 6-months 60.0% vs. 66.7%). There were no fatalities in either group. CONCLUSIONS: Our study did not demonstrate differences in rejection with basiliximab compared to rATG. Mortality did not differ, but basiliximab-treated patients had fewer infections and infection-related hospitalizations than those treated with rATG. Larger studies with longer durations are needed to more completely describe the differences in rejection and infectious outcomes.

Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles.

Transmembrane proteins known as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control the movement of Na+ and K+ ions across cellular membranes. HCN channels are known to be involved in crucial physiological functions in regulating neuronal excitability and rhythmicity, and pacemaker activity in the heart. Although HCN channels have been relatively well investigated in the brain, their distribution and function in the retina have received less attention, remaining their physiological roles to be comprehensively understood. Also, because recent studies reported HCN channels have been somewhat linked with the dysfunction of photoreceptors which are affected by retinal diseases, investigating HCN channels in the retina may offer valuable insights into disease mechanisms and potentially contribute to identifying novel therapeutic targets for retinal degenerative disorders. This paper endeavors to summarize the existing literature on the distribution and function of HCN channels reported in the vertebrate retinas of various species and discuss the potential implications for the treatment of retinal diseases. Then, we recapitulate current knowledge regarding the function and regulation of HCN channels, as well as their relevance to various neurological disorders.

Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147).

PURPOSE: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. PATIENTS AND METHODS: We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A). The main outcome was efficacy, defined as histologic regression to CIN1 or less. Secondary outcomes were HPV clearance and tolerability. Exploratory objectives included the comparison of cervical CD4/CD8 T-cell infiltration at baseline, mid-study, and posttreatment by flow cytometry among study arms. RESULTS: Of the 114 evaluable patients 77% and 23% harbored CIN2 and CIN3, respectively. Regression to CIN1 or less was observed in 95% of patients in the imiquimod group (Arm B) compared with 79% in the control/surveillance (Arm A); P = 0.043 and 84% in the imiquimod+9vHPV group (Arm C; P = 0.384 vs. Arm A). Neither of the treatment-arm differences from Arm A reached the prespecified α = 0.025 significance level. No significant differences were noted in the secondary outcome of rate of HPV clearance. The number of tissue-resident memory CD4/CD8 T cells in cytobrush samples demonstrated a >5-fold increase in Arm B/imiquimod when compared with Arm A/surveillance (P < 0.01). In contrast, there was no significant difference in T-cell responses among participants in Arm C when compared with Arm A. Imiquimod treatment was well tolerated. CONCLUSIONS: Although imiquimod induced a higher regression to CIN1 or less and significant increases in CD4/CD8 T cells infiltrating the cervix, it did not meet its prespecified statistical outcome for efficacy. A higher regression rate than expected was observed in the surveillance arm of this prospective trial. Future clinical trials with imiquimod targeting CIN3 patients are warranted.

Propensity weighted analysis of chemical venous thromboembolism prophylaxis agents in isolated severe traumatic brain injury: An EAST sponsored multicenter study.

BACKGROUND: In patients with severe traumatic brain injury (TBI), clinicians must balance preventing venous thromboembolism (VTE) with the risk of intracranial hemorrhagic expansion (ICHE). We hypothesized that low molecular weight heparin (LMWH) would not increase risk of ICHE or VTE as compared to unfractionated heparin (UH) in patients with severe TBI. METHODS: Patients ≥ 18 years of age with isolated severe TBI (AIS ≥ 3), admitted to 24 level I and II trauma centers between January 1, 2014 to December 31, 2020 and who received subcutaneous UH and LMWH injections for chemical venous thromboembolism prophylaxis (VTEP) were included. Primary outcomes were VTE and ICHE after VTEP initiation. Secondary outcomes were mortality and neurosurgical interventions. Entropy balancing (EBAL) weighted competing risk or logistic regression models were estimated for all outcomes with chemical VTEP agent as the predictor of interest. RESULTS: 984 patients received chemical VTEP, 482 UH and 502 LMWH. Patients on LMWH more often had pre-existing conditions such as liver disease (UH vs LMWH 1.7 % vs. 4.4 %, p = 0.01), and coagulopathy (UH vs LMWH 0.4 % vs. 4.2 %, p < 0.001). There were no differences in VTE or ICHE after VTEP initiation. There were no differences in neurosurgical interventions performed. There were a total of 29 VTE events (3 %) in the cohort who received VTEP. A Cox proportional hazards model with a random effect for facility demonstrated no statistically significant differences in time to VTE across the two agents (p = 0.44). The LMWH group had a 43 % lower risk of overall ICHE compared to the UH group (HR = 0.57: 95 % CI = 0.32-1.03, p = 0.062), however was not statistically significant. CONCLUSION: In this multi-center analysis, patients who received LMWH had a decreased risk of ICHE, with no differences in VTE, ICHE after VTEP initiation and neurosurgical interventions compared to those who received UH. There were no safety concerns when using LMWH compared to UH. LEVEL OF EVIDENCE: Level III, Therapeutic Care Management.

Safety and Effectiveness of Track Cauterization for Lung Cryoablation.

PURPOSE: To evaluate the safety and effectiveness of track cauterization for lung cryoablation through comparison of postprocedural adverse event (AE) rates. MATERIALS AND METHODS: Fifty-nine patients who underwent 164 percutaneous lung cryoablation procedures between 2013 and 2018 were included in this retrospective study. The study cohort was subdivided by whether track cauterization was conducted or not at the end of the procedure. The study cohort was also subdivided by the number of probes (1-2 probes vs 3-4 probes). Postablation AE rates were assessed by immediate and delayed (at 1 month or later) AEs, pneumothorax, hemothorax, pleural effusion, and whether intervention was required. Univariate and multivariate logistic regression analyses were used to compare differences in AE rates. RESULTS: Patients who underwent procedures with track cautery were 2.6 times less likely to exhibit pleural effusion (P = .017). Patients who underwent procedures conducted with a higher number of probes were 3.8 times more likely to receive interventions (P < .001), 1.6 times more likely to experience pneumothorax (P = .037), and 2.1 times more likely to experience pleural effusion (P = .003). History of lung surgery, increased number of probes, size of the probe, and absence of track cautery were noted to be significant predictors of AEs and need for interventions (all P < .05). CONCLUSIONS: Track cauterization in lung cryoablation was proven to reduce pleural effusion, but no difference in pneumothorax or delayed AEs was noted. The use of fewer probes was associated with a lower rate of AEs.

Leukotriene B4: A potential mediator and biomarker for cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the leading cause of long-term graft failure and mortality after heart transplantation. Effective preventive and treatment options are not available to date, largely because underlying mechanisms remain poorly understood. We studied the potential role of leukotriene B4 (LTB4), an inflammatory lipid mediator, in the development of CAV. METHODS: We used an established preclinical rat CAV model to study the role of LTB4 in CAV. We performed syngeneic and allogeneic orthotopic aortic transplantation, after which neointimal proliferation was quantified. Animals were then treated with Bestatin, an inhibitor of LTB4 synthesis, or vehicle control for 30 days post-transplant, and evidence of graft CAV was determined by histology. We also measured serial LTB4 levels in a cohort of 28 human heart transplant recipients with CAV, 17 matched transplant controls without CAV, and 20 healthy nontransplant controls. RESULTS: We showed that infiltration of the arterial wall with macrophages leads to neointimal thickening and a rise in serum LTB4 levels in our rat model of CAV. Inhibition of LTB4 production with the drug Bestatin prevents development of neointimal hyperplasia, suggesting that Bestatin may be effective therapy for CAV prevention. In a parallel study of heart transplant recipients, we found nonsignificantly elevated plasma LTB4 levels in patients with CAV, compared to patients without CAV and healthy, nontransplant controls. CONCLUSIONS: This study provides key evidence supporting the role of the inflammatory cytokine LTB4 as an important mediator of CAV development and provides preliminary data suggesting the clinical benefit of Bestatin for CAV prevention.

Reducing inpatient opioid consumption after caesarean delivery: effects of an opioid stewardship programme and racial impact in a community hospital.

Caesarean section is the most common inpatient surgery in the USA, with more than 1.1 million procedures in 2020. Similar to other surgical procedures, healthcare providers rely on opioids for postoperative pain management. However, current evidence shows that postpartum patients usually experience less pain due to pregnancy-related physiological changes. Owing to the current opioid crisis, public health agencies urge providers to provide rational opioid prescriptions. In addition, a personalised postoperative opioid prescription may benefit racial minorities since research shows that this population receives fewer opioids despite greater pain levels. Our project aimed to reduce inpatient opioid consumption after caesarean delivery within 6 months of the implementation of an opioid stewardship programme.A retrospective analysis of inpatient opioid consumption after caesarean delivery was conducted to determine the baseline, design the opioid stewardship programme and set goals. The plan-do-study-act method was used to implement the programme, and the results were analysed using a controlled interrupted time-series method.After implementing the opioid stewardship programme, we observed an average of 80% reduction (ratio of geometric means 0.2; 95% CI 0.2 to 0.3; p<0.001) in inpatient opioid consumption. The institution designated as control did not experience relevant changes in inpatient opioid prescriptions during the study period. In addition, the hospital where the programme was implemented was unable to reduce the difference in inpatient opioid demand between African Americans and Caucasians.Our project showed that an opioid stewardship programme for patients undergoing caesarean delivery can effectively reduce inpatient opioid use. PDSA, as a quality improvement method, is essential to address the problem, measure the results and adjust the programme to achieve goals.