Design of the first fusion experiment to achieve target energy gain G>1.

In this work we present the design of the first controlled fusion laboratory experiment to reach target gain G>1 N221204 (5 December 2022) [Phys. Rev. Lett. 132, 065102 (2024)10.1103/PhysRevLett.132.065102], performed at the National Ignition Facility, where the fusion energy produced (3.15 MJ) exceeded the amount of laser energy required to drive the target (2.05 MJ). Following the demonstration of ignition according to the Lawson criterion N210808, experiments were impacted by nonideal experimental fielding conditions, such as increased (known) target defects that seeded hydrodynamic instabilities or unintentional low-mode asymmetries from nonuniformities in the target or laser delivery, which led to reduced fusion yields less than 1 MJ. This Letter details design changes, including using an extended higher-energy laser pulse to drive a thicker high-density carbon (also known as diamond) capsule, that led to increased fusion energy output compared to N210808 as well as improved robustness for achieving high fusion energies (greater than 1 MJ) in the presence of significant low-mode asymmetries. For this design, the burnup fraction of the deuterium and tritium (DT) fuel was increased (approximately 4% fuel burnup and a target gain of approximately 1.5 compared to approximately 2% fuel burnup and target gain approximately 0.7 for N210808) as a result of increased total (DT plus capsule) areal density at maximum compression compared to N210808. Radiation-hydrodynamic simulations of this design predicted achieving target gain greater than 1 and also the magnitude of increase in fusion energy produced compared to N210808. The plasma conditions and hotspot power balance (fusion power produced vs input power and power losses) using these simulations are presented. Since the drafting of this manuscript, the results of this paper have been replicated and exceeded (N230729) in this design, together with a higher-quality diamond capsule, setting a new record of approximately 3.88MJ of fusion energy and fusion energy target gain of approximately 1.9.

Emission lines due to ionizing radiation from a compact object in the remnant of Supernova 1987A.

The nearby Supernova 1987A was accompanied by a burst of neutrino emission, which indicates that a compact object (a neutron star or black hole) was formed in the explosion. There has been no direct observation of this compact object. In this work, we observe the supernova remnant with JWST spectroscopy, finding narrow infrared emission lines of argon and sulfur. The line emission is spatially unresolved and blueshifted in velocity relative to the supernova rest frame. We interpret the lines as gas illuminated by a source of ionizing photons located close to the center of the expanding ejecta. Photoionization models show that the line ratios are consistent with ionization by a cooling neutron star or a pulsar wind nebula. The velocity shift could be evidence for a neutron star natal kick.

Reduced mixing in inertial confinement fusion with early-time interface acceleration.

In inertial confinement fusion (ICF) implosions, the interface between the cryogenic DT fuel and the ablator is unstable to shock acceleration (the Richtmyer-Meshkov instability, RM) and constant acceleration (Rayleigh-Taylor instability, RT). Instability growth at this interface can reduce the final compression, limiting fusion burnup. If the constant acceleration is in the direction of the lighter material (negative Atwood number), the RT instability produces oscillatory motion that can stabilize against RM growth. Theory and simulations suggest this scenario occurred at early times in some ICF experiments on the National Ignition Facility, possibly explaining their favorable performance compared to one-dimensional simulations. This characteristic is being included in newer, lower adiabat designs, seeking to improve compression while minimizing ablator mixing into the fuel.

Amygdalar activity measured using FDG-PET/CT at head and neck cancer staging independently predicts survival.

IMPORTANCE: The mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood. OBJECTIVE: To test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival. DESIGN: Retrospective cohort study. SETTING: Academic Medical Center (Massachusetts General Hospital, Boston). PARTICIPANTS: 240 patients with head and neck cancer (HNCA) who underwent 18F-FDG-PET/CT imaging as part of initial cancer staging. MEASUREMENTS: 18F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV). RESULTS: Among individuals with HNCA (age 59±13 years; 30% female), 67 died over a median follow-up period of 3 years (IQR: 1.7-5.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P<0.05 each). In adjusted and unadjusted analyses, AmygA associated with subsequent mortality (HR [95% CI]: 1.35, [1.07-1.70], P = 0.009); the association persisted in stratified subset analyses restricted to patients with advanced cancer stage (P<0.001). Individuals within the highest tertile of AmygA experienced a 2-fold higher mortality rate compared to others (P = 0.01). The median progression-free survival was 25 months in patients with higher AmygA (upper tertile) as compared with 36.5 months in other individuals (HR for progression or death [95%CI], 1.83 [1.24-2.68], P = 0.001). CONCLUSIONS AND RELEVANCE: AmygA, quantified on routine 18F-FDG-PET/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival.

Alpha heating of indirect-drive layered implosions on the National Ignition Facility.

In order to understand how close current layered implosions in indirect-drive inertial confinement fusion are to ignition, it is necessary to measure the level of alpha heating present. To this end, pairs of experiments were performed that consisted of a low-yield tritium-hydrogen-deuterium (THD) layered implosion and a high-yield deuterium-tritium (DT) layered implosion to validate experimentally current simulation-based methods of determining yield amplification. The THD capsules were designed to reduce simultaneously DT neutron yield (alpha heating) and maintain hydrodynamic similarity with the higher yield DT capsules. The ratio of the yields measured in these experiments then allowed the alpha heating level of the DT layered implosions to be determined. The level of alpha heating inferred is consistent with fits to simulations expressed in terms of experimentally measurable quantities and enables us to infer the level of alpha heating in recent high-performing implosions.

Can Crude Oil Exploration Influence the Phytochemicals and Bioactivity of Medicinal Plants? A Case of Nigerian Vernonia amygdalina and Ocimum gratissimum.

The Nigerian Niger-Delta crude oil exploration often results in spills that affect indigenous medicinal plant biodiversity, likely changing the phytochemical profile of surviving species, their bioactivity or toxicity. In crude oil-rich Kokori and crude oil-free Abraka, classic examples of indigenous plants occupying the medicine-food interface include Vernonia amygdalina (VAL) and Ocimum gratissimum leaves (OGL). These plants are frequently utilised during pregnancy and in anaemia. To date, no scientific investigation has been reported on the potential changes to the phytochemical or bioactivity of the study plants. To discuss the similarities and dissimilarities in antisickling bioactivity and phytochemicals in VAL and OGL collected from Kokori (VAL-KK and OGL-KK) and Abraka (VAL-AB and OGL-AB), in silico, in vitro and comparative UPLC-QTOF-MS analysis was performed. Nine unique compounds were identified in OGL-KK, which have never been reported in the literature, while differences in antisickling potentials were observed in VAL-KK, OGL-KK and, VAL-AB, OGL-AB. Our findings show that VAL-AB and OGL-AB are richer and more diverse in phytochemicals and displayed a slightly higher antisickling activity than VAL-KK and OGL-KK. Ligand-based pharmacophore modelling was performed to understand the potential compounds better; this study may provide a basis for explaining the effect of crude oil spills on secondary metabolites and a reference for further research.

Pediatric Groin Surgeries: A Comparison of Analgesic Effects of Caudal Block and Inguinal Field Block Using Plain Bupivacaine.

Introduction: There is a paucity of studies in the West African sub-region which have compared both the intraoperative and postoperative analgesic effects of caudal block and inguinal field block using plain bupivacaine in groin surgeries in children. The study aimed to compare the duration of analgesia and complications of caudal block and inguinal field block in pediatric groin surgeries. Patients and Methods: This was a prospective, double-blind randomized study conducted at a tertiary health institution in North Central, Nigeria, over a period of 6 months. A total of 74 children scheduled for day case groin surgeries for inguinal hernia, hydrocoele and palpable undescended testis were recruited into the study. The effectiveness of the analgesic effect was assessed by measuring serum cortisol levels before surgery (i.e. baseline at 8am), 5minutes after caudal block or inguinal field block, and 1-hour after surgery. Post-operative pain was determined using FLACC score (Face, Legs, Activity, Crying and Consolability) every 15 minutes till 6 hours after surgery when the patients were discharged home and the caregivers measured the patients' pain scores using the FLACC score every 1 hour to a maximum duration of 10 hours after surgery. Data obtained from the study was entered into the study proforma and analysed using IBM SPSS version 21.0. The P value was considered statistically significant at <0.05. Results: A total of 74 patients were recruited for this study, with 68 males (91.9%) and 6 females (8.1%). The children's age range was 6 months to 7 years, with a mean age of 3.35 ± 1.90 years. The mean basal serum cortisol levels of the caudal block group and inguinal block group were 11.15 ± 5.38 µg/dL and 10.79 ± 4.92µg/d respectively (p-value = 0.767). Five minutes after caudal block, the mean serum cortisol level was 10.50 ± 5.39µg/dL while inguinal field block was 10.63 ± 4.68µg/dL (p-value = 0.288). The mean serum cortisol level obtained one hour after each procedure was 9.34 ± 4.05 µg/dL for the caudal block group and 10.00 ± 3.56 µg/dL in the inguinal field block group with p-value = 0.275.Using the FLACC score, the mean duration of analgesia in caudal block group was 372.00 ± 71.55 minutes and was inguinal field block group was 387.43 ± 62.65 minutes with a p-value = 0.116. There was no anaesthetic technique related complications that was recorded in both caudal block group and inguinal group during the study period. Conclusion: This study demonstrated that caudal block and inguinal field block using plain bupivacaine provided comparable duration of analgesia in paediatric groin surgeries. Therefore, caudal block or inguinal field block using plain bupivacaine should be recommended for both intraoperative and postoperative analgesia in elective paediatric groin surgeries.

Experimental achievement and signatures of ignition at the National Ignition Facility.

An inertial fusion implosion on the National Ignition Facility, conducted on August 8, 2021 (N210808), recently produced more than a megajoule of fusion yield and passed Lawson's criterion for ignition [Phys. Rev. Lett. 129, 075001 (2022)10.1103/PhysRevLett.129.075001]. We describe the experimental improvements that enabled N210808 and present the first experimental measurements from an igniting plasma in the laboratory. Ignition metrics like the product of hot-spot energy and pressure squared, in the absence of self-heating, increased by ∼35%, leading to record values and an enhancement from previous experiments in the hot-spot energy (∼3×), pressure (∼2×), and mass (∼2×). These results are consistent with self-heating dominating other power balance terms. The burn rate increases by an order of magnitude after peak compression, and the hot-spot conditions show clear evidence for burn propagation into the dense fuel surrounding the hot spot. These novel dynamics and thermodynamic properties have never been observed on prior inertial fusion experiments.

Design of an inertial fusion experiment exceeding the Lawson criterion for ignition.

We present the design of the first igniting fusion plasma in the laboratory by Lawson's criterion that produced 1.37 MJ of fusion energy, Hybrid-E experiment N210808 (August 8, 2021) [Phys. Rev. Lett. 129, 075001 (2022)10.1103/PhysRevLett.129.075001]. This design uses the indirect drive inertial confinement fusion approach to heat and compress a central "hot spot" of deuterium-tritium (DT) fuel using a surrounding dense DT fuel piston. Ignition occurs when the heating from absorption of α particles created in the fusion process overcomes the loss mechanisms in the system for a duration of time. This letter describes key design changes which enabled a ∼3-6× increase in an ignition figure of merit (generalized Lawson criterion) [Phys. Plasmas 28, 022704 (2021)1070-664X10.1063/5.0035583, Phys. Plasmas 25, 122704 (2018)1070-664X10.1063/1.5049595]) and an eightfold increase in fusion energy output compared to predecessor experiments. We present simulations of the hot-spot conditions for experiment N210808 that show fundamentally different behavior compared to predecessor experiments and simulated metrics that are consistent with N210808 reaching for the first time in the laboratory "ignition."

Artificial intelligence and machine learning algorithms for early detection of skin cancer in community and primary care settings: a systematic review.

Skin cancers occur commonly worldwide. The prognosis and disease burden are highly dependent on the cancer type and disease stage at diagnosis. We systematically reviewed studies on artificial intelligence and machine learning (AI/ML) algorithms that aim to facilitate the early diagnosis of skin cancers, focusing on their application in primary and community care settings. We searched MEDLINE, Embase, Scopus, and Web of Science (from Jan 1, 2000, to Aug 9, 2021) for all studies providing evidence on applying AI/ML algorithms to the early diagnosis of skin cancer, including all study designs and languages. The primary outcome was diagnostic accuracy of the algorithms for skin cancers. The secondary outcomes included an overview of AI/ML methods, evaluation approaches, cost-effectiveness, and acceptability to patients and clinicians. We identified 14 224 studies. Only two studies used data from clinical settings with a low prevalence of skin cancers. We reported data from all 272 studies that could be relevant in primary care. The primary outcomes showed reasonable mean diagnostic accuracy for melanoma (89·5% [range 59·7-100%]), squamous cell carcinoma (85·3% [71·0-97·8%]), and basal cell carcinoma (87·6% [70·0-99·7%]). The secondary outcomes showed a heterogeneity of AI/ML methods and study designs, with high amounts of incomplete reporting (eg, patient demographics and methods of data collection). Few studies used data on populations with a low prevalence of skin cancers to train and test their algorithms; therefore, the widespread adoption into community and primary care practice cannot currently be recommended until efficacy in these populations is shown. We did not identify any health economic, patient, or clinician acceptability data for any of the included studies. We propose a methodological checklist for use in the development of new AI/ML algorithms to detect skin cancer, to facilitate their design, evaluation, and implementation.

The efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm.

BACKGROUND: Coronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with calcium channel blockers (CCBs) and long-acting nitrates among patients 5-FU associated coronary vasospasm. METHODS: We conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety. RESULTS: Among 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23-0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34-1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26). CONCLUSION: Re-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy.

Moringa oleifera Seed at the Interface of Food and Medicine: Effect of Extracts on Some Reproductive Parameters, Hepatic and Renal Histology.

The lipid-rich Seed of Moringa oleifera has been promoted as an effective water clarifier. Aside its vital nutritional application as an emerging food additive, the seed has continued to gain a wider acceptance in various global ethnomedicines for managing several communicable and lifestyle diseases, howbeit, its potential toxic effect, particularly on fertility and pregnancy outcomes has remained uninvestigated; the effect of Moringa oleifera seed (MOSE) aqueous-methanol extracts on fertility and pregnancy outcome, was investigated in vivo using female Wistar rats that were divided into 50, 100, 300 and 500 mg per kilogram body weight. Group six was given Moringa oleifera seed treated water ad-libitum (ad-libitum group). Organs harvested for histological assessment included ovary, uterus, liver and kidney. In addition to HPLC fingerprint and a preliminary peptide detection, we determined the physico-chemical characteristics and mineral content of MOSE using standard methods. Data were analyzed with significance at p ≤ 0.05. There was no significant difference in the estrus cycle, mating index, gestation survival index, gestation index, fertility index and sex ratio among all groups. Gestation length was reduced in some groups. While the male pup birth weight was comparable among the different groups, female pups birth weights were significantly reduced in 50 and 100 mg groups. Anogenital distance indices of female pups in ad libitum group were significantly increased. Pathologies were observed in liver and kidneys of dams while kidneys of pups presented a dose dependent reduction in the number of glomeruli. There were no observed pathological changes in the ovary and uterus. This study showed for the first time in rodents, that the lipid-rich MOSE is unsafe to the kidney of rodents while the lipid-free MOSE appears to be safe at doses up to 300 mg/kg body weight. Findings from this study suggested that the female pups were masculinized. In conclusion, the lipid-rich seed extracts of MOSE appear to be unsafe during pregnancy, induce hepatic and renal toxicity while the lipid-free MOSE excludes inherent toxicity as the hydrophobic part has been linked to toxicity as observed in this study due to the developmental programming effect on female offspring in rodents.

Idiopathic Intracranial Hypertension is Associated with a Higher Burden of Visible Cerebral Perivascular Spaces: The Glymphatic Connection.

BACKGROUND AND PURPOSE: Research suggests a connection between idiopathic intracranial hypertension and the cerebral glymphatic system. We hypothesized that visible dilated perivascular spaces, possible glymphatic pathways, would be more prevalent in patients with idiopathic intracranial hypertension. This prevalence could provide a biomarker and add evidence to the glymphatic connection in the pathogenesis of idiopathic intracranial hypertension. MATERIALS AND METHODS: We evaluated 36 adult (older than 21 years of age) patients with idiopathic intracranial hypertension and 19 controls, 21-69 years of age, who underwent a standardized MR imaging protocol that included high-resolution precontrast T2- and T1-weighted images. All patients had complete neuro-ophthalmic examinations for papilledema. The number of visible perivascular spaces was evaluated using a comprehensive 4-point qualitative rating scale, which graded the number of visible perivascular spaces in the centrum semiovale and basal ganglia; a 2-point scale was used for the midbrain. Readers were blinded to patient diagnoses. Continuous variables were compared using a Student t test. RESULTS: The mean number of visible perivascular spaces overall was greater in the idiopathic intracranial hypertension group than in controls (4.5 [SD, 1.9] versus 2.9 [SD, 1.9], respectively; P = .004). This finding was significant for centrum semiovale idiopathic intracranial hypertension (2.3 [SD, 1.4] versus controls, 1.3 [SD, 1.1], P = .003) and basal ganglia idiopathic intracranial hypertension (1.7 [SD, 0.6] versus controls, 1.2 [SD, 0.7], P = .009). There was no significant difference in midbrain idiopathic intracranial hypertension (0.5 [SD, 0.5] versus controls, 0.4 [SD, 0.5], P = .47). CONCLUSIONS: Idiopathic intracranial hypertension is associated with an increased number of visible intracranial perivascular spaces. This finding provides insight into the pathophysiology of idiopathic intracranial hypertension, suggesting a possible relationship between idiopathic intracranial hypertension and glymphatic dysfunction and providing another useful biomarker for the disease.

Outcomes of a smartphone-based application with live health-coaching post-percutaneous coronary intervention.

BACKGROUND: The interval between inpatient hospitalization for symptomatic coronary artery disease (CAD) and post-discharge office consultation is a vulnerable period for adverse events. METHODS: Content was customized on a smartphone app-based platform for hospitalized patients receiving percutaneous coronary intervention (PCI) which included education, tracking, reminders and live health coaches. We conducted a single-arm open-label pilot study of the app at two academic medical centers in a single health system, with subjects enrolled 02/2018-05/2019 and 1:3 propensity-matched historical controls from 01/2015-12/2017. To evaluate feasibility and efficacy, we assessed 30-day hospital readmission (primary), outpatient cardiovascular follow-up, and cardiac rehabilitation (CR) enrollment as recorded in the health system. Outcomes were assessed by Cox Proportional Hazards model. FINDINGS: 118 of 324 eligible (36·4%) 21-85 year-old patients who underwent PCI for symptomatic CAD who owned a smartphone or tablet enrolled. Mean age was 62.5 (9·7) years, 87 (73·7%) were male, 40 of 118 (33·9%) had type 2 diabetes mellitus, 68 (57·6%) enrolled underwent PCI for MI and 59 (50·0%) had previously known CAD; demographics were similar among matched historical controls. No significant difference existed in all-cause readmission within 30 days (8·5% app vs 9·6% control, ARR -1.1% absolute difference, 95% CI -7·1-4·8, p = 0·699) or 90 days (16·1% app vs 19·5% control, p = 0.394). Rates of both 90-day CR enrollment (HR 1·99, 95% CI 1·30-3·06) and 1-month cardiovascular follow up (HR 1·83, 95% CI 1·43-2·34) were greater with the app. Weekly engagement at 30- and 90-days, as measured by percentage of weeks with at least one day of completion of tasks, was mean (SD) 73·5% (33·9%) and 63·5% (40·3%). Spearman correlation analyses indicated similar engagement across age, sex, and cardiovascular risk factors. INTERPRETATIONS: A post-PCI smartphone app with live health coaches yielded similarly high engagement across demographics and safely increased attendance in cardiac rehabilitation. Larger prospective randomized controlled trials are necessary to test whether this app improves cardiovascular outcomes following PCI. FUNDING: National Institutes of Health, Boston Scientific. CLINICAL TRIAL REGISTRATION: NCT03416920 (https://clinicaltrials.gov/ct2/show/NCT03416920).

Community interventions for improving adult mental health: mapping local policy and practice in England.

BACKGROUND: Public mental health (PMH) aims to improve wellbeing and prevent poor mental health at the population level. It is a global challenge and a UK priority area for action. Communities play an important role in the provision of PMH interventions. However, the evidence base concerning community-based PMH interventions is limited, meaning it is challenging to compare service provision to need. Without this, the efficient and equitable provision of services is hindered. Here, we sought to map the current range of community-based interventions for improving mental health and wellbeing currently provided in England to inform priority areas for policy and service intervention. METHOD: We adopted an established mapping exercise methodology, comparing service provision with demographic and deprivation statistics. Five local authority areas of England were selected based on differing demographics, mental health needs and wider challenging circumstances (i.e. high deprivation). Community-based interventions were identified through: 1) desk-based research 2) established professional networks 3) chain-referral sampling of individuals involved in local mental health promotion and prevention and 4) peer researchers' insight. We included all community-based, non-clinical interventions aimed at adult residents operating between July 2019 and May 2020. RESULTS: 407 interventions were identified across the five areas addressing 16 risk/protective factors for PMH. Interventions for social isolation and loneliness were most prevalent, most commonly through social activities and/or befriending services. The most common subpopulations targeted were older adults and people from minority ethnic backgrounds. Interventions focusing on broader structural and environmental determinants were uncommon. There was some evidence of service provision being tailored to local need, though this was inconsistent, meaning some at-risk groups such as men or LGBTQ+ people from minority ethnic backgrounds were missed. Interventions were not consistently evaluated. CONCLUSIONS: There was evidence of partial responsiveness to national and local prioritising. Provision was geared mainly towards addressing social and individual determinants of PMH, suggesting more integration is needed to engage wider service providers and policy-makers in PMH strategy and delivery at the community level. The lack of comprehensive evaluation of services to improve PMH needs to be urgently addressed to determine the extent of their effectiveness in communities they serve.

The Intersection of Type 2 Myocardial Infarction and Heart Failure.

Background Type 2 myocardial infarction (T2MI) is common and associated with high cardiovascular event rates. However, the relationship between T2MI and heart failure (HF) is uncertain. Methods and Results We identified patients with T2MI at a large tertiary hospital between October 2017 and May 2018. Patient characteristics, causes of T2MI, and subsequent HF hospitalizations were determined by physician chart review. We identified 359 patients with T2MI over the study period; 184 patients had a history of HF. Among patients with ejection fraction (EF) assessment (N=180), the majority had preserved EF (N=107; 59.4%), followed by reduced EF (N=54; 30.0%), and mid-range EF (N=19; 10.6%). Acute HF was the most common cause of T2MI (20.9%). Of those whose T2MI was precipitated by HF (N=75), the mean EF was 53.0±16.8% and 16 (21.3%) were de novo diagnoses of HF. Among patients with T2MI who were discharged alive with available follow-up (N=289), 5.5% were hospitalized with acute HF within 30 days, 17.3% within 180 days, and 22.1% within 1 year. In subgroup analyses, among patients with T2MI with prevalent or new HF (N=161), the rate of HF hospitalization at 1 year was 34.2%, considerably higher than those with T2MI and no HF diagnosis at discharge (7.0%; N=9/128). Conclusions Index presentations of HF or worsening chronic HF represent the most common causes of T2MI. ≈1 in 5 patients with T2MI will be readmitted for HF within 1 year of their event. Strategies to prevent HF events after a T2MI are needed.

The Incidence, Risk Factors, and Outcomes With 5-Fluorouracil-Associated Coronary Vasospasm.

BACKGROUND: Coronary vasospasm is a recognized side effect of 5-FU (fluorouracil). There are limited and conflicting data on the incidence, risk factors and prognostic effect of 5-FU associated vasospasm. OBJECTIVES: To assess the incidence, risk factors and prognostic implications of 5-FU coronary vasospasm among patients receiving 5-FU regimens at a single tertiary care center. METHODS: We conducted a retrospective analysis of all patients who received 5-FU at a single academic center from January 2009 to July 2019. Vasospasm was defined as the occurrence of a typical chest pain syndrome in the presence of 5-FU. The presence of associated electrocardiogram (ECG) changes and/or elevated biomarkers was used to further confirm the diagnosis. Patients with vasospasm were compared to patients treated with 5-FU without vasospasm in a 1:2 ratio. Data regarding demographics, medical history, and follow-up were collected by manual chart review. RESULTS: From approximately 4019 individual patients who received 5-FU from 2009 to 2019 at a single center, 87 (2.16%) developed vasospasm. Patients who developed vasospasm were younger (58±13 vs. 64±13 years, P = 0.001), and were less likely to have any cardiovascular risk factors (70.1% vs. 84.5%, P = 0.007). Patients with vasospasm and patients without vasospasm were otherwise similar in terms of types of cancer, stage of cancer, sex, and race. There was no significant difference in progression-free survival, overall mortality or cancer specific mortality between patients who developed vasospasm versus those who did not. CONCLUSION: In a large, single-center report of 5-FU associated vasospasm, patients who developed vasospasm were younger, had lower rates of traditional cardiovascular risk factors and had no significant difference in progression-free or overall survival compared to those who did not develop vasospasm.

Anti-sickling activities of two isolated compounds from the root of Combretum racemosum P. beauv. (Combretaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Evaluation of plants such as Combretum racemosum with claimed traditional use in the management of sickle cell anaemia in Nigeria and other parts of West Africa could serve as a useful research strategy in the search for potential anti-sickling drugs and templates. AIM OF THE STUDY: This study aimed at evaluating the antisickling potential of C. racemosum by activity-guided purification and isolation of its active constituents. MATERIALS AND METHODS: Crude methanol extract of the root of C. racemosum and the fractions obtained by partitioning with chloroform, ethyl acetate, and aqueous were investigated for anti-sickling activity against sodium metabisulphite induced sickling of sickle cell haemoglobin (HbSS). Repeated chromatographic separations were conducted on the most active chloroform fraction to purify and isolate bioactive compounds for further tests for anti-sickling activity. The characterization of the isolated compounds was done by mass spectrometry (FD+MS) and nuclear magnetic resonance (1HNMR) spectroscopy. RESULTS: The chloroform fraction (FA) (% sickled erythrocyte ranged from 3.0 to 34.1) exhibited better anti-sickling activity than aqueous (% sickled erythrocyte ranged from 38.9 to 51.5) as well as the crude methanol (% sickled erythrocyte ranged from 19.1 to 30.4). Hence, the phytochemical investigation was focused on the chloroform fraction, which led to the identification of two ellagic acid derivatives (3,3',4'-tri-O-methyl ellagic acid (A) and 3,3'-di-O- methyl ellagic acid (B). The two isolated compounds possessed good, comparable anti-sickling activities with compound A exhibiting a slightly better in vitro activity. CONCLUSION: This paper reports for the first time anti-sickling principles from C. racemosum and therefore, provided some justification for the ethnomedicinal use of the plant in the management of sickle cell disease.

Electrocardiographic features of immune checkpoint inhibitor associated myocarditis.

BACKGROUND: Myocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis. METHODS: From an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested. RESULTS: Both the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, p<0.001 and p=0.009, respectively). In contrast, the QTc interval at the time of myocarditis (435±39 ms) was not increased compared with pre-myocarditis baseline (422±27 ms, p=0.42). A prolonged QRS duration conferred an increased risk of subsequent MACE (HR 3.28, 95% CI 1.98 to 5.62, p<0.001). After adjustment, each 10 ms increase in the QRS duration conferred a 1.3-fold increase in the odds of MACE (95% CI 1.07 to 1.61, p=0.011). Conversely, there was no association between the QTc interval and MACE among men (HR 1.33, 95% CI 0.70 to 2.53, p=0.38) or women (HR 1.48, 95% CI 0.61 to 3.58, p=0.39). CONCLUSIONS: The QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification.