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Australia is developing a national performance framework aimed at measuring health outcomes across the health system. Clinical registries provide a clinically credible means of monitoring health care processes and outcomes, yet only five Australian registries currently have national coverage. At a national level, clinical registry development should be prioritised to target conditions or procedures that are suspected of being associated with large variations in processes or outcomes of care and that impact significantly on health care costs and patient morbidity. Registries should also aim to capture information across care interfaces and to monitor the medium and long-term safety and effectiveness of specific devices, procedures and drugs. [ABSTRACT FROM AUTHOR]

Background: Quantitative myocardial PET perfusion imaging requires partial volume corrections.Methods: Patients underwent ECG-gated, rest-dipyridamole, myocardial perfusion PET using Rb-82 decay corrected in Bq/cc for diastolic, systolic, and combined whole cycle ungated images. Diastolic partial volume correction relative to systole was determined from the systolic/diastolic activity ratio, systolic partial volume correction from phantom dimensions comparable to systolic LV wall thicknesses and whole heart cycle partial volume correction for ungated images from fractional systolic-diastolic duration for systolic and diastolic partial volume corrections.Results: For 264 PET perfusion images from 159 patients (105 rest-stress image pairs, 54 individual rest or stress images), average resting diastolic partial volume correction relative to systole was 1.14 ± 0.04, independent of heart rate and within ±1.8% of stress images (1.16 ± 0.04). Diastolic partial volume corrections combined with those for phantom dimensions comparable to systolic LV wall thickness gave an average whole heart cycle partial volume correction for ungated images of 1.23 for Rb-82 compared to 1.14 if positron range were negligible as for F-18.Conclusion: Quantitative myocardial PET perfusion imaging requires partial volume correction, herein demonstrated clinically from systolic/diastolic absolute activity ratios combined with phantom data accounting for Rb-82 positron range. [ABSTRACT FROM AUTHOR]

This study was designed to assess the effect of cancer treatments on the natural and assisted reproductive potential of men. A cohort of men with cancer, in whom radiotherapy and/or chemotherapy was planned, were invited to participate. Twenty-two pre- and post-treatment semen samples were analysed. The reproductive potential of participants was assessed with respect to the current range of fertility treatment options available. Abnormal sperm concentrations were found in 27% of patients pre-treatment compared to 68% post-treatment following a mean latency of 20 months from treatment. Fifty-nine percent of patients experienced a clinically significant decrease in sperm, concentration following radiotherapy and/or chemotherapy; 23% developed azoospermia following treatment. Eighty-two percent of patients with testicular malignancy had oligo- or azoospermia post-treatment. Only one patient had a clinically significant reduction in the percentage of motile spermatozoa post-treatment. Cryopreservation of semen prior to treatment improved the fertility prospects of 55% of patients. Intracytoplasmic sperm injection (ICSI) enhanced the fertility prospects of a further 14%. In the absence of, or after depletion of, cryopreserved semen, ICSI could enhance the fertility prospects of 45% of patients. Fertilization has been achieved by ICSI using spermatozoa retrieved by testicular biopsy from an azoospermic testicular cancer survivor 8 years after chemotherapy. It was concluded that chemotherapy and/or radiotherapy may depress semen concentration to the extent of rendering a man infertile. The severity of the reduction in sperm concentration following treatment is unpredictable but likely to be most severe in those with testicular malignancy and those treated with radiotherapy or alkylating chemotherapy agents. Not all men are keen to undergo an appraisal of their post-treatment fertility potential, for reasons which are unclear. Improving awareness and education of patients concerning the effects of both cancer and cancer treatments on reproductive potential is essential. With the advent of ICSI, it is possible to offer a very reasonable chance of conception in all men with cancer who present for cryopreservation of semen prior to treatment in whom spermatozoa (even in very low concentrations) are present in the ejaculate. [ABSTRACT FROM AUTHOR]

Background: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes., Methods: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI., Results: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61-0.69]; P <0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79-0.84]; P <0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50-0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00-2.97])., Conclusions: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789317., Competing Interests: Dr Collet reports receiving research grants from Biosensors, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; consultancy fees from HeartFlow, OpSens Medical, Abbott Vascular, and Philips Volcano; and has patents pending on diagnostic methods for coronary artery disease. Dr Munhoz reports a research grant provided by the CardioPath PhD programme and speaker fees from Abbott Vascular. Dr Mizukami reports receiving research grants from Boston Scientific and speaker fees from Abbott Vascular, CathWorks, and Boston Scientific. Dr Matsuo has received consulting fees from Kaneka and Zeon and speaker’s fees from Abbott Medical Japan, Boston Scientific, Philips, and Amgen. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Biscaglia received research grants provided by Sahajanand Medical Technologies, Medis Medical Imaging, Eukon Srl, Siemens Healthineers, General Electric Healthcare, and Insight Lifetech. Dr Engstrøm reports speaker and advisory board fees from Abbott, Boston Scientific, and Novo Nordisk. Dr Leone reports receiving consultancy fees from Abbott and honoraria for sponsored symposia from Abbott, Medtronic, and Abiomed. Dr Fearon receives institutional research support from Abbott, Boston Scientific, and Medtronic and has consulting relationships with CathWorks and Siemens and stock options from HeartFlow. Dr Christiansen has received consulting fees from Abbott Medical Denmark A/S. Dr Yong has received minor honoraria from Abbott Vascular and research grants from Abbott Vascular and Philips. Dr Escaned is supported by the Intensification of Research Activity project INT22/00088 from the Spanish Instituto de Salud Carlos III and received speaker and advisory board member fees from Abbott and Philips. Dr Storozhenko reports a grant provided by the EAPCI Fellowship Programme. Dr West is an employee of Abbott Vascular. Dr De Potter is a paid consultant for Biosense Webster and receives grant support (institutional) and consultancy fees (institutional) from Abbott. Dr Berry receives research funding from the British Heart Foundation (grants RE/18/6134217, BHF/FS/17/26/32744, and PG/19/28/34310) and is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Coroventis Research, GlaxoSmithKline, HeartFlow, Menarini, Novartis, Servier, Siemens Healthcare, and Valo Health. Dr Collison has received consulting fees from Abbott. Dr Johnson has received consultancy or speaker fees from Abbott Vascular, Boston Scientific, Medtronic, Shockwave, and Terumo, and research grants from Abbott Vascular. Dr Amano reports receiving lecture fees from Astellas Pharma, Astra Zeneca, Bayer, Daiichi Sankyo, and Bristol Myers Squibb. Dr Perera has received research grant support from Abbott Vascular, HeartFlow, and Philips. Dr Jeremias has received consulting fees from Canon Medical, Artrya Medical, and Boston Scientific. Dr Ali reports institutional grant support from Abbott, Abiomed, Acist, Amgen, Boston Scientific, CathWorks, Canon Medical, Conavi, HeartFlow, Inari, Medtronic, the US National Institutes of Health, Nipro, OpSens Medical, Medis, Philips, Shockwave, Siemens, SpectraWAVE, and Teleflex; consulting fees from Abiomed, Astra Zeneca, Boston Scientific, CathWorks, OpSens Medical, Philips, and Shockwave; and equity in Elucid, Lifelink, SpectraWAVE, Shockwave, and VitalConnect. Dr Pijls has received research grants from Abbott and Hexacath; consultancy fees from Abbott, GE, Philips, and HeartFlow; and has equity in General Electric, Philips, and HeartFlow. Dr De Bruyne reports receiving consultancy fees from Boston Scientific and Abbott and research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular. Dr Johnson received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; has received significant institutional research support from St Jude Medical (CONTRAST [Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02184117]) and Philips Volcano (DEFINE-FLOW [Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02328820]) for other studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm (now commercialized under 510[k] K191008); and has patents pending on diagnostic methods for quantifying aortic stenosis and TAVI physiology and on methods to correct pressure tracings from fluid-filled catheters.

Background: Data on cardiac positron emission tomography (PET) in liver transplantation (LT) candidates are limited with no prior study accounting for poorly metabolized caffeine reducing stress perfusion., Method: Consecutive LT candidates (n = 114) undergoing cardiac rest/stress PET were instructed to abstain from caffeine for 2 days extended to 5 and 7 days. Due to persistently high prevalence of measurable blood caffeine after 5-day caffeine abstinence, dipyridamole (n = 41) initially used was changed to dobutamine (n = 73). Associations of absolute flow, coronary flow reserve (CFR), detectable blood caffeine, and Modified End-Stage Liver Disease (MELD) score for liver failure severity were evaluated. Coronary flow data of LT candidates were compared to non-LT control group (n = 102 for dipyridamole, n = 29 for dobutamine)., Results: Prevalence of patients with detectable blood caffeine was 63.3%, 36.7% and 33.3% after 2-, 5- and 7-day of caffeine abstinence, respectively. MELD score was associated with detectable caffeine (odd ratio 1.18,P < 0.001). CFR was higher during dipyridamole stress without-caffeine versus with-caffeine (2.22 ± 0.80 vs 1.55 ± 0.37,P = 0.048) but lower than dobutamine stress (2.22 ± 0.80 vs 2.82 ± 1.02,P = 0.026). Mediation analysis suggested that the dominant association between CFR and MELD score in dipyridamole group derived from caffeine-impaired CFR and liver failure/caffeine interaction. CFR in LT candidates was lower than non-LT control population in both dipyridamole and dobutamine group., Conclusion: We demonstrate exceptionally high prevalence of detectable blood caffeine in LT candidates undergoing stress PET myocardial perfusion imaging resulting in reduced CFR with dipyridamole compared to dobutamine. The delayed caffeine clearance in LT candidates makes dobutamine a preferred stress agent in this population., (Copyright © 2024 University of Texas Health Science Center at Houston. Published by Elsevier Inc. All rights reserved.)

Objective: To examine factors associated with fertility following hysterosalpingography (HSG) using an oil-soluble contrast medium (OSCM)., Design: In a prospective cohort study on 196 women undergoing OSCM HSG, we showed that iodine excess was almost universal (98%) and mild subclinical hypothyroidism was frequent (38%). Here, we report the analyses of secondary outcomes examining factors associated with the likelihood of pregnancy following the HSG., Setting: Auckland, New Zealand (2019-2021)., Sample: 196 women with primary or secondary infertility who underwent OSCM HSG., Methods: Baseline and serial urine iodine concentrations (UIC) and thyroid function tests were measured over six months following the HSG. Pregnancy and treatment with levothyroxine during the study period were documented., Results: Following OSCM HSG, pregnancy rates were 49% in women aged <40 years (77/158) but considerably lower (16%) among those ≥40 years (6/38). Similarly, live birth rates were markedly lower in women ≥40 years (17%; 1/6) versus <40 years (73%; 56/77). 29% of participants were iodine deficient at baseline despite advice recommending iodine fortification. Following HSG, the likelihood of pregnancy in women with moderate iodine deficiency was 64% higher than in women with normal iodine levels (p=0.048). Among women aged <40 years who had subclinical hypothyroidism (n=75), levothyroxine treatment was associated with higher pregnancy rates compared to untreated women [63% (26/48) vs 37% (10/27), respectively; p=0.047]., Conclusion: OSCM HSG was associated with higher pregnancy rates in women ≤40 than in those aged >40 years. Iodine deficiency was relatively common in this cohort, and increased iodine levels from OSCM exposure may contribute to the improved fertility observed with this procedure., Trial Registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12620000738921) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000738921., Competing Interests: NJ is involved in research with the University of Auckland and the University of Adelaide, which are funded by Guerbet. NJ has undertaken paid consultancies for Guerbet. DM and PH are involved with a University of Auckland study on Lipiodol safety through an unrestricted independent grant to the Liggins institute from Guerbet. PH has received fees for speaking in two webinars sponsored by Guerbet. RS and JP have been paid for presenting and being an advisory board member by Guerbet. RS, JP, and NJ undertake Lipiodol HSGs as a part of their profession. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The funder Guerbet had no role in the study design, conduction of the study, data analyses or interpretation, manuscript preparation, decision to publish it, or dissemination of study findings., (Copyright © 2024 Mathews, Peart, Sim, Johnson, O’Sullivan, Derraik and Hofman.)

Study Question: What is the efficacy and safety of long-term treatment (up to 2 years) with relugolix combination therapy (CT) in women with moderate to severe endometriosis-associated pain?, Summary Answer: For up to 2 years, treatment with relugolix CT improved menstrual and non-menstrual pain, dyspareunia, and function in women with endometriosis; after an initial decline of <1%, the mean bone mineral density (BMD) remained stable with continued treatment., What Is Known Already: Endometriosis is a chronic condition characterized by symptoms of dysmenorrhea, non-menstrual pelvic pain (NMPP), and dyspareunia, which have a substantial impact on the lives of affected women, their partners, and families. SPIRIT 1 and 2 were phase 3, randomized, double-blind, placebo-controlled studies of once-daily relugolix CT (relugolix 40 mg, oestradiol 1 mg, norethisterone acetate 0.5 mg) in premenopausal women (age 18-50 years) with endometriosis and moderate-to-severe dysmenorrhea and NMPP. These trials demonstrated a significant improvement of dysmenorrhea, NMPP, and dyspareunia in women treated with relugolix CT, with minimal decline (<1%) in BMD versus placebo at 24 weeks., Study Design, Size, Duration: Patients participating in this open-label, single-arm, long-term extension (LTE) study of the 24-week SPIRIT pivotal studies (SPIRIT 1 and 2) received up to an additional 80 weeks of once-daily oral relugolix CT treatment between May 2018 and January 2023., Participants/materials, Setting, Methods: Premenopausal women with confirmed endometriosis and moderate to severe dysmenorrhea and NMPP who completed the 24-week pivotal studies (SPIRIT 1 and 2 trials; Giudice et al., 2022) and who met all entry criteria were eligible to enrol. Two-year results were analysed by treatment group based on original randomization in pivotal studies: relugolix CT, delayed relugolix CT (relugolix 40 mg monotherapy for 12 weeks, followed by relugolix CT), or placebo→relugolix CT (placebo for 24 weeks followed by relugolix CT). The primary endpoints of the LTE study were the proportion of dysmenorrhea and NMPP responders at Week 52 and Week 104/end-of-treatment (EOT). A responder was a participant who achieved a predefined, clinically meaningful reduction from baseline in Numerical Rating Scale (NRS) scores (0 = no pain, 10 = worst pain imaginable) for the specific pain type with no increase in analgesic use. The predefined clinically meaningful threshold for dysmenorrhea was 2.8 points and for NMPP was 2.1 points. Secondary efficacy endpoints included change from baseline in Endometriosis Health Profile-30 (EHP-30) pain domain scores, a measure of the effects of endometriosis-associated pain on daily activities (function), NRS scores for dysmenorrhea, NMPP, dyspareunia, and overall pelvic pain, and analgesic/opioid use. Safety endpoints included adverse events and changes in BMD., Main Results and the Role of Chance: Of 1261 randomized patients, 1044 completed the pivotal studies, 802 enrolled in the LTE, 681 completed 52 weeks of treatment, and 501 completed 104 weeks of treatment. Demographics and baseline characteristics of the extension population were consistent with those of the original randomized population. Among patients randomized to relugolix CT at pivotal study baseline who continued in the LTE (N = 277), sustained improvements in endometriosis-associated pain were demonstrated through 104 weeks. The proportion of responders at Week 104/EOT for dysmenorrhea and NMPP was 84.8% and 75.8%, respectively. Decreases in dyspareunia and improvement in function assessed by EHP-30 pain domain were also sustained over 2 years. At Week 104/EOT, 91% of patients were opioid-free and 75% of patients were analgesic-free. Relugolix CT over 104 weeks was well tolerated with a safety profile consistent with that observed over the first 24 weeks. After initial least squares mean BMD loss <1% at Week 24, BMD plateaued at Week 36 and was sustained for the duration of 104 weeks of treatment. Efficacy and safety results were generally consistent in women in the placebo→relugolix CT and delayed relugolix CT groups., Limitations, Reasons for Caution: The study was conducted as an open-label study without a control group over the 80 weeks of the extension period. Of the 802 patients who were enrolled in this LTE study, 681 patients (84.9%) and 501 patients (62.5%) of patients completed 52 and 104 weeks of treatment, respectively. In addition, there currently are no comparative data to other hormonal medications. Finally, a third (37.4%) of the study population terminated participation early., Wider Implications of the Findings: In conclusion, relugolix CT offers an additional option to help address an important unmet clinical need for effective, safe, and well-tolerated medical treatments for endometriosis that can be used longer-term, reducing the need for opioids and improving quality of life. The findings from this study may help support the care of women with endometriosis seeking longer-term effective medical management of their symptoms., Study Funding/competing Interest(s): This study was funded by Myovant Sciences GmbH (now Sumitomo Pharma Switzerland GmbH). C.M.B. reports fees from Myovant, grants from Bayer Healthcare, fees from ObsEva, and Chair of ESHRE Endometriosis Guideline Group (all funds went to the University of Oxford); N.P.J. reports personal fees from Myovant Sciences, during the conduct of the study, personal fees from Guerbet, personal fees from Organon, personal fees from Roche Diagnostics; S.A.-S. reports personal fees from Myovant Sciences, personal fees from Bayer, personal fees from Abbvie, personal fees from UpToDate; J.S.P., and R.B.W. are employees and shareholders of Myovant Sciences; J.C.A.F. and S.J.I. are shareholders of Myovant Sciences (but at time of publicaion are no longer employess of Myovant Sciences); M.S.A. and K.W. have no conflicts to declare; V.M. is a consultant to Myovant; L.C.G. reports personal fees from Myovant Sciences, Inc and Bayer. The authors did not receive compensation for manuscript writing, review, and revision., Trial Registration Number: NCT03654274., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Introduction and Objectives: Several studies have investigated the effectiveness of fractional flow reserve (FFR) guidance in improving clinical outcomes after myocardial revascularization, yielding conflicting results. The aim of this study was to compare clinical outcomes in patients with coronary artery disease following FFR-guided or angiography-guided revascularization., Methods: Both randomized controlled trials (RCTs) and nonrandomized intervention studies were included. Coprimary endpoints were all-cause death, myocardial infarction, and major adverse cardiovascular events (MACE). The study is registered with PROSPERO (CRD42022344765)., Results: A total of 30 studies enrolling 393 588 patients were included. FFR-guided revascularization was associated with significantly lower rates of all-cause death (OR, 0.63; 95%CI, 0.53-0.73), myocardial infarction (OR, 0.70; 95%CI, 0.59-0.84), and MACE (OR, 0.77; 95%CI, 0.70-0.85). When only RCTs were considered, no significant difference between the 2 strategies was observed for any endpoints. However, the use of FFR was associated with reduced rates of revascularizations and treated lesions. Metaregression suggested that the higher the rate of revascularized patients the lower the benefit of FFR guidance on MACE reduction compared with angiography guidance (P=.012). Similarly, higher rates of patients with acute coronary syndromes were associated with a lower benefit of FFR-guided revascularization (P=.039)., Conclusions: FFR-guided revascularization was associated with lower rates of all-cause death, myocardial infarction and MACE compared with angiographic guidance, with RCTs and nonrandomized intervention studies yielding conflicting data. The benefits of FFR-guidance seem to be less evident in studies with high revascularization rates and with a high prevalence of patients with acute coronary syndrome., (Copyright © 2024. Published by Elsevier España, S.L.U.)

The impact of aortic valve stenosis (AS) extends beyond the vicinity of the narrowed leaflets into the left ventricle (LV) and into the systemic vasculature because of highly unpredictable valve behavior and complex blood flow in the ascending aorta that can be attributed to the strong interaction between the narrowed cusps and the ejected blood. These effects can become exacerbated during exercise and may have implications for disease progression, accurate diagnosis, and timing of intervention. In this 3-D patient-specific study, we employ strongly coupled fluid-structure interaction (FSI) modeling to perform a comprehensive biomechanical evaluation of systolic ejection dynamics in a stenosed aortic valve (AV) during increasing LV contraction. Our model predictions reveal that the heterogeneous ∆P vs. Q relationship that was observed in our previous clinical study can be attributed to a non-linear increase (by ~ 1.5-fold) in aortic valve area as LV heart rate increases from 70 to 115 bpm. Furthermore, our results show that even for a moderately stenotic valve, increased LV contraction during exercise can lead to high-velocity flow turbulence (Re = 11,700) in the aorta similar to that encountered with a severely stenotic valve (Re ~ 10,000), with concomitant greater viscous loss (~3-fold increase) and elevated wall stress in the ascending aorta. Our FSI predictions also reveal that individual valve cusps undergo distinct and highly non-linear increases (>100%) in stress during exercise, potentially contributing to progressive calcification. Such quantitative biomechanical evaluations from realistic FSI workflows provide insights into disease progression and can be integrated with current stress testing for AS patients to comprehensively predict hemodynamics and valve function under both baseline and exercise conditions., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

During the past 30 years, fractional flow reserve (FFR) has moved from animal models to class IA recommendations in guidelines. However, the FLOWER-MI, RIPCORD-2, FUTURE, and FAME 3 trials in 2021 were "negative"-has FFR exceeded its expiration date? We critically examine these randomized trials in order to draw insights not just about FFR but also about study design and interpretation. Are all randomized trials created equal? No, rather we must focus on discordant decisions between angiography and FFR and highlight clinical endpoints that can be improved by percutaneous coronary intervention instead of medical therapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization., Methods: Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0., Results: Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025)., Conclusions: Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: In 2019, the CDC expanded their recommendations for human papillomavirus (HPV) vaccination beyond age 26 years to include shared clinical decision-making (SCDM) among adults aged 27-45 years ("mid-adults"). The purpose of this study was to describe HPV vaccination status among mid-adult women before the implementation of SCDM for HPV vaccination. Methods: A cross-sectional survey was conducted during 2016-2019 in Connecticut, United States, and enrolled women born in 1981 or later (birth cohorts eligible for HPV vaccination). This analysis was restricted to participants aged 27 years and older at the time of the survey. Correlates of vaccination status, sources of vaccine information, and reasons for not receiving the vaccine were examined. Results: Among 298 participants, 64.4% had not received HPV vaccine. Other than age (younger age was associated with being vaccinated), no other demographic or behavioral correlates were associated with vaccination. Compared with unvaccinated women, vaccinated women were more likely to have heard about the HPV vaccine from a doctor (odds ratio [OR] = 3.45, 95% confidence interval [CI]: 2.00-5.88) and less likely to have heard about it from television (OR = 0.23, 95% CI: 0.13-0.41). The main reasons for not being vaccinated were "vaccine not offered" (48%) and "too old" (40%). Conclusions: A majority of mid-adult women in this study were not previously vaccinated against HPV, signaling the large opportunity for SCDM with this population. This may be facilitated by ensuring health care providers and mid-adult women know about the availability and potential benefits of HPV vaccination to inform decision making.

The production of fossil fuels, including oil, gas, and coal, retains a dominant share in US energy production and serves as a major anthropogenic source of methane, a greenhouse gas with a high warming potential. In addition to directly emitting methane into the air, fossil fuel production can release methane into groundwater, and that methane may eventually reach the atmosphere. In this study, we collected 311 water samples from an unconventional oil and gas (UOG) production region in Pennsylvania and an oil and gas (O&G) and coal production region across Ohio and West Virginia. Methane concentration was negatively correlated to distance to the nearest O&G well in the second region, but such a correlation was shown to be driven by topography as a confounding variable. Furthermore, sulfate concentration was negatively correlated with methane concentration and with distance to coal mining in the second region, and these correlations were robust even when considering topography. We hypothesized that coal mining enriched sulfate in groundwater, which in turn inhibited methanogenesis and enhanced microbial methane oxidation. Thus, this study highlights the complex interplay of multiple factors in shaping groundwater methane concentrations, including biogeochemical conversion, topography, and conventional fossil extraction.

Background: The interplay between coronary hemodynamics and plaque characteristics remains poorly understood., Objectives: The aim of this study was to compare atherosclerotic plaque phenotypes between focal and diffuse coronary artery disease (CAD) defined by coronary hemodynamics., Methods: This multicenter, prospective, single-arm study was conducted in 5 countries. Patients with functionally significant lesions based on an invasive fractional flow reserve ≤0.80 were included. Plaque analysis was performed by using coronary computed tomography angiography and optical coherence tomography. CAD patterns were assessed using motorized fractional flow reserve pullbacks and quantified by pullback pressure gradient (PPG). Focal and diffuse CAD was defined according to the median PPG value., Results: A total of 117 patients (120 vessels) were included. The median PPG was 0.66 (IQR: 0.54-0.75). According to coronary computed tomography angiography analysis, plaque burden was higher in patients with focal CAD (87% ± 8% focal vs 82% ± 10% diffuse; P = 0.003). Calcifications were significantly more prevalent in patients with diffuse CAD (Agatston score per vessel: 51 [IQR: 11-204] focal vs 158 [IQR: 52-341] diffuse; P = 0.024). According to optical coherence tomography analysis, patients with focal CAD had a significantly higher prevalence of circumferential lipid-rich plaque (37% focal vs 4% diffuse; P = 0.001) and thin-cap fibroatheroma (TCFA) (47% focal vs 10% diffuse; P = 0.002). Focal disease defined by PPG predicted the presence of TCFA with an area under the curve of 0.73 (95% CI: 0.58-0.87)., Conclusions: Atherosclerotic plaque phenotypes associate with intracoronary hemodynamics. Focal CAD had a higher plaque burden and was predominantly lipid-rich with a high prevalence of TCFA, whereas calcifications were more prevalent in diffuse CAD. (Precise Percutaneous Coronary Intervention Plan [P3]; NCT03782688)., Competing Interests: Funding and Author Disclosures The study was sponsored by the Cardiac Research Institute Aalst with unrestricted grants from HeartFlow Inc. Dr Mizukami has received consulting fees from Zeon Medical and HeartFlow Inc; and speaker fees from Abbott Vascular. Dr Leipsic is a consultant and has holding stock options in Circle CVI and HeartFlow Inc; has received a research grant from GE; and modest speaker fees from GE and Philips. Drs Sonck and Munhoz have received research grants provided by the Cardiopath Ph.D. program. Dr Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow Inc. Dr Otake has received research grants from Abbott Vascular; and speaker fees from HeartFlow Inc and Abbott Vascular. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Koo has received institutional research grants from HeartFlow Inc. Dr Maeng has received advisory board and lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Boston Scientific, and Novo Nordisk; and research grants from Bayer and Philips Healthcare. Dr Jensen has received unrestricted institutional research grants from Siemens and HeartFlow Inc. Dr Andreini has received research grants from GE Healthcare and Bracco. Dr Shinke has received research grants from Boston Scientific and Abbott Vascular. CT is an employee of HeartFlow Inc. Dr Barbato has received speaker fees from Boston Scientific, Abbott Vascular, and GE. Dr Johnson has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; significant institutional research support from St. Jude Medical (CONTRAST [Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?]; NCT02184117) and Philips/Volcano Corporation (DEFINE-FLOW [Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses]; NCT02328820) for studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm commercialized under 510(k) K191008; and has pending patents on diagnostic methods for quantifying aortic stenosis and transcatheter aortic valve replacement physiology, as well as algorithms to correct pressure tracings from fluid-filled catheters. Dr De Bruyne has received consultancy fees from Boston Scientific and Abbott Vascular; research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, and Abbott Vascular; and owns equity in Siemens, GE, Philips, HeartFlow Inc, Edwards Life Sciences, Bayer, Sanofi, and Celyad. Dr Collet has received research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, and Abbott Vascular; and consultancy fees from HeartFlow Inc, OpSens, Abbott Vascular, and Philips Volcano. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum., Aim: The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR., Methods: This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least 1 lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events., Results: Recruitment is ongoing and is expected to be completed in the second half of 2023., Conclusion: This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the preprocedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes., Competing Interests: Disclosures AML reports receiving consultancy fees from Abbott and honoraria for sponsored symposiums from Abbott, Medtronic and Abiomed. DM report a research grant provided by the Cardiopath PhD program and speaker fees from Abbott Vascular. BDB reports receiving consultancy fees from Boston Scientific and Abbott and research grants from Coroventis Research, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc. and Abbott Vascular. CC reports receiving research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc. and Abbott Vascular; and consultancy fees from Heart Flow Inc, Opsens, Abbott Vascular and Philips Volcano. BK has received consulting fees from Canon Medical, Abbott and Medtronic. AI has received consulting fees from Canon, Artrya Medical and Boston Scientific. TWJ has received consultancy/speaker fees from Abbott Vascular, Boston Scientific, Medtronic, Shockwave, Terumo and research grants from Abbott Vascular. NPJ received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; has received significant institutional research support from St. Jude Medical (CONTRAST, NCT02184117) and Philips Volcano Corporation (DEFINE-FLOW, NCT02328820) for other studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm (now commercialized under 510(k) K191008); and has patents pending on diagnostic methods for quantifying aortic stenosis and TAVI physiology, and on methods to correct pressure tracings from fluid-filled catheters. SB received research grants provided by Sahajanand Medical Technologies Ltd (SMT), Medis Medical Imaging Systems, Eukon S.r.l., Siemens Healthineers, General Electric (GE) Healthcare, and Insight Lifetech. EHC has received consulting fees from Abbott Medical Denmark A/S. CB receives research funding from the British Heart Foundation (RE/18/6134217, BHF/FS/17/26/32744, PG/19/28/34310). Colin Berry is employed by the University of Glasgow which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Coroventis, GSK, HeartFlow, Menarini, Novartis, Servier, Siemens Healthcare, and Valo Health. WFF receives institutional research support from Abbot, Boston, and Medtronic and has consulting relationships with CathWorks and Siemens and stock options with HeartFlow. TE reports speakers and advisory board fees from Abbott, Boston and Novo Nordisk. AY has received minor honoraria from Abbott Vascular, and research grants from Abbott Vascular and Philips. DC has received consulting fees from Abbott. TS reports a grant provided by the EAPCI Fellowship Programme., (Copyright © 2023 Elsevier Inc. All rights reserved.)