Intraoperative hypotension and the risk of acute kidney injury following liver transplantation

Background: Acute kidney injury (AKI) is a frequent adverse outcome following liver transplantation (LT) with a multifactorial etiology. It is critical to identify modifiable risk factors to mitigate the risk. One key area of interest is the role of intraoperative hypotension, which remains relatively unexplored in liver transplant cohorts. Methods: This was a retrospective observational cohort study of 1292 adult patients who underwent LT (between 2009 and 2019). Multivariable logistic regression analysis was used to explore the association between intraoperative hypotension, quantified by time duration (in min) under various mean arterial pressure (MAP) thresholds, and the primary outcome of early postoperative AKI according to the KDIGO criteria. Results: AKI occurred in 40% of patients and was independently associated with greater than 20 min spent below MAP thresholds of 55 mm Hg (adjusted OR = 1.866; 95% CI = 1.037–3.44; P = 0.041) and 50 mm Hg (adjusted OR = 1.801; 95% CI = 1.087–2.992; P = 0.023). Further sensitivity analyses demonstrated that the association between intraoperative hypotension and postoperative AKI was accentuated after restricting the analysis to patients with a normal preoperative renal function. Conclusions: Prolonged (>20 min) intraoperative hypotension (below a MAP of 55 mm Hg) was independently associated with AKI following LT, after adjusting for several known confounders

F-18-Fluorodeoxyglucose Positron Emission Tomography Imaging-Assisted Management of Patients With Severe Left Ventricular Dysfunction and Suspected Coronary Disease A Randomized, Controlled Trial (PARR-2)

ObjectivesWe conducted a randomized trial to assess the effectiveness of F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)-assisted management in patients with severe ventricular dysfunction and suspected coronary disease.BackgroundSuch patients may benefit from revascularization, but have significant perioperative morbidity and mortality. F-18-fluorodeoxyglucose PET can detect viable myocardium that might recover after revascularization.MethodsIncluded were patients with severe left ventricular (LV) dysfunction and suspected coronary disease being considered for revascularization, heart failure, or transplantation work-ups or in whom PET was considered potentially useful. Patients were stratified according to recent angiography or not, then randomized to management assisted by FDG PET (n = 218) or standard care (n = 212). The primary outcome was the composite of cardiac death, myocardial infarction, or recurrent hospital stay for cardiac cause, within 1 year.ResultsAt 1 year, the cumulative proportion of patients who had experienced the composite event was 30% (PET arm) versus 36% (standard arm) (relative risk 0.82, 95% confidence interval [CI] 0.59 to 1.14; p = 0.16). The hazard ratio (HR) for the composite outcome, PET versus standard care, was 0.78 (95% CI 0.58 to 1.1; p = 0.15); for patients that adhered to PET recommendations for revascularization, revascularization work-up, or neither, HR = 0.62 (95% CI 0.42 to 0.93; p = 0.019); in those without recent angiography, for cardiac death, HR = 0.4 (95% CI 0.17 to 0.96; p = 0.035).ConclusionsThis study did not demonstrate a significant reduction in cardiac events in patients with LV dysfunction and suspected coronary disease for FDG PET-assisted management versus standard care. In those who adhered to PET recommendations and in patients without recent angiography, significant benefits were observed. The utility of FDG PET is best realized in this subpopulation and when adherence to recommendations can be achieved

Markov modeling of disease progression and mortality

Prognostic studies of progression and mortality in different diseases are essential to understand the role of particular prognostic factors and, thus, improve prognosis and ultimately help selecting appropriate interventions. Yet, such studies often face serious limitations of available data and/or of the existing statistical methods. One difficulty concerns separating the effects of putative prognostic factors on different clinical endpoints or “competing events” such as e.g. disease recurrence vs. recurrence-free death, or death due to disease vs. death due to other causes. This issue becomes even more challenging because data sources, such as cancer registries, often record only the date of death but not the cause of death. This can lead to bias in assessing the role of prognostic factors whose impact on the disease-specific mortality is quite different from their impact on all-cause mortality. It is important, therefore, to use methods that can deal accurately and efficiently with both (i) alternative pathways of disease progression, and (ii) unknown causes of death. The aforementioned challenges are addressed by 3 manuscripts. Previous empirical studies have suggested the potential advantages of using multi-state Markov models, over conventional time-to-event methods, to analyze competing risks and multi-state pathways of disease progression. In the 1st paper, I attempted to systematically assess, through a series of simulations, the performance of Markov models in this context and confirmed the accuracy of both point estimates of the regression coefficients and hypothesis tests. On the other hand, Relative Survival regression models have been developed, in the context of single-endpoint time-to-event analyses, to correct the regression coefficients for the unknown causes of death. Yet, no existing statistical model permits simultaneous combination of the advantages of both (i) Markov multi-state modeling, and (ii) Relative Survival. Therefore, in theLes études pronostiques sur l'évolution et la mortalité de certaines pathologies sont essentielles pour comprendre le rôle de certains facteurs pronostiques et ainsi, améliorer le pronostic et finalement aider dans le choix des interventions thérapeutiques appropriées. Jusqu'à présent, les études de ce type ont été souvent confrontées à d'importantes limitations dans les données et/ou les méthodes statistiques disponibles. Une des difficultés concerne la discrimination, pour un même facteur pronostique, de ses effets sur différents critères cliniques ou événements concurrents, comme la récidive de la maladie vs le décès sans récidive, ou le décès dû à la pathologie vs le décès dû à d'autres causes. Ce problème devient d'autant plus important que les sources de données, comme les registres, enregistrent souvent uniquement la date de décès mais pas la cause. Ceci peut conduire à des biais dans l'évaluation du rôle des facteurs pronostiques dont l'effet sur la mortalité spécifique dû à la pathologie est différent de celui sur la mortalité toutes causes confondues. Il est donc important d'utiliser des méthodes qui puissent prendre en compte correctement à la fois (i) les différentes évolutions possibles de la pathologie et (ii) l'absence de la connaissance de la cause de décès. Les problèmes méthodologiques mentionnés précédemment sont traités dans 3 articles. Les études empiriques précédentes ont suggéré des avantages potentiels à utiliser les modèles multi-états de Markov à la place des modèles de survie conventionnels dans l'analyse des risques compétitifs et des différentes phases possibles d'évolution d'une pathologie. Le premier article tente d'évaluer méthodiquement, à l'aide de simulations, les performances des modèles de Markov dans ce contexte et confirme l'exactitude à la fois de l'estimation des coefficients de la régression et des tests d'hypothèse. D'un autre coté, les mo

Examining treatment targets and equity in bone-active medication use within secondary fracture prevention: a systematic review and meta-analysis

Purpose: This systematic review seeks to evaluate the proportion of fragility fracture patients screened in secondary fracture prevention programs who were indicated for pharmacological treatment, received prescriptions for bone-active medications, and initiated the prescribed medication. Additionally, the study aims to analyze equity in pharmacological treatment by examining equity-related variables including age, sex, gender, race, education, income, and geographic location.Methods: We conducted a systematic review to ascertain the proportion of fragility fracture patients indicated for treatment who received prescriptions and/or initiated bone-active medication through secondary fracture prevention programs. We also examined treatment indications reported in studies and eligibility criteria to confirm patients who were eligible for treatment. To compute the pooled proportions for medication prescription and initiation, we carried out a single group proportional meta-analysis. We also extracted the proportions of patients who received a prescription and/or began treatment based on age, sex, race, education, socioeconomic status, location, and chronic conditionsResults: This review included 122 studies covering 114 programs. The pooled prescription rate was 77%, and the estimated medication initiation rate was 71%. Subgroup analysis revealed no significant difference in treatment initiation between the Fracture Liaison Service and other programs. Across all studies, age, sex, and socioeconomic status were the only equity variables reported in relation to treatment outcomes.Conclusion: Our systematic review emphasizes the need for standardized reporting guidelines in post-fracture interventions. Moreover, considering equity stratifiers in the analysis of health outcomes will help address inequities and improve the overall quality and reach of secondary fracture prevention programs

Coerced consent in clinical research: study protocol for a randomized controlled trial

Abstract Background Despite the low-risk nature of participation in most clinical anesthesia trials, subject recruitment on the same day as surgery is often restricted due to the concerns of researchers and local research ethics boards that same-day consent may not afford adequate time and opportunity for patients to weigh and make decisions, as well as perceptions of patient vulnerability immediately prior to surgery that could impact the voluntary nature and the rigor of the informed consent process. However, specialties such as anesthesiology, critical care, interventional radiology, and emergency medicine have a varied pattern of practice and patient acquaintance that does not typically afford the luxury of time or, in many cases, advance consent for participation in research. Indeed, the initial encounter between anesthesiologists and patients undergoing elective procedures routinely occurs on the day of surgery. Concerns of coercion related to same-day consent for clinical anesthesia research trials have not been borne out in the literature, and represent a significant obstacle to clinical researchers, as well as to the patients who are denied opportunities for potential benefit through participation in research studies. Methods We describe the protocol for a prospective randomized controlled trial examining the voluntariness of patient consent, solicited either in advance of surgery or on the same day, to participate in an anesthesia research study at Women’s College Hospital. One hundred fourteen patients scheduled to undergo ambulatory anterior cruciate ligament repair facilitated by general anesthesia with an adductor canal block will be randomized for recruitment either (a) in the pre-operative assessment clinic before the day of surgery or (b) on the day of surgery, to be approached for consent to participate in a fabricated research study of adjunct medications in adductor canal blocks. Regardless of allocation, patients in both groups will receive the same routine standard of care and will complete a post-operative questionnaire to signal perceptions of undue influence in the process of providing informed consent for the fabricated trial. Discussion This study will inform trial design and practice guidelines surrounding the amount of time patients ought to be afforded in order to make durable decisions to participate (or not) in clinical research studies. This is expected to impact trial recruitment in a variety of clinical settings where researchers have only brief opportunities to interface with patients. Trial registration The trial was registered prospectively on the Open Science Framework (OSF), registration #46twc, on 2023-Mar-17

Long-Term Outcomes in Adult Patients With Pulmonary Hypertension After Percutaneous Closure of Atrial Septal Defects

BACKGROUND Pulmonary hypertension (PH), recently redefined as mean pulmonary arterial pressure >20 mm Hg (PH$_{20}$), may be observed in patients with atrial septal defects (ASD). We aimed to determine the effect of preprocedural PH$_{20}$ status on outcomes among patients undergoing ASD closure. METHODS Study population was selected from a retrospective registry of adult patients who underwent percutaneous ASD closure from 1998 to 2016 from a single center and had right heart catheterizations during the procedure. The clinical registry was linked to administrative databases to capture short- and long-term outcomes. RESULTS We included a total of 632 ASD closure patients of whom 359 (56.8%) had PH$_{20}$. The mean follow-up length was 7.6±4.6 years. Patients with PH$_{20}$ were older (mean age 56.5 versus 43.1 years, P<0.001) and a higher prevalence of comorbidities including hypertension (54.3% versus 21.6%, P<0.001) and diabetes (18.1% versus 5.9%, P<0.001) than those without PH. In a Cox proportional hazards model after covariate adjustment, patients with PH had a significantly higher risk of developing major adverse cardiac and cerebrovascular events (heart failure, stroke, myocardial infarction, or cardiovascular mortality), with hazards ratio 2.45 (95% CI, 1.4-4.4). When applying the prior, mean pulmonary arterial pressure ≥25 mm Hg (PH$_{25}$) cutoff, a significantly higher hazard of developing major adverse cardiac and cerebrovascular events was observed in PH versus non-PH patients. CONCLUSIONS ASD patients with PH undergoing closure suffer from more comorbidities and worse long-term major adverse cardiac and cerebrovascular events outcomes, compared with patients without PH. The use of the new PH$_{20}$ definition potentially dilutes the effect of this serious condition on outcomes in this population

Associations of serum levels of sex hormones in follicular and luteal phases of the menstrual cycle with breast tissue characteristics in young women

Background: In previous work in young women aged 15-30 years we measured breast water and fat using MR and obtained blood for hormone assays on the same day in the follicular phase of the menstrual cycle. Only serum growth hormone levels and sex hormone binding globulin (SHBG) were significantly associated with percent breast water after adjustment for covariates. The sex hormones estradiol, progesterone and testosterone were not associated with percent water in the breast in the follicular phase of the menstrual cycle. In the present study we have examined the association of percent breast water with serum levels of sex hormones in both follicular and luteal phase of the menstrual cycle. Methods: In 315 healthy white Caucasian young women aged 15-30 with regular menstrual cycles who had not used oral contraceptives or other hormones in the previous 6 months, we used MR to determine percent breast water, and obtained blood samples for hormone assays within 10 days of the onset of the most recent menstrual cycle (follicular phase) of the cycle on the same day as the MR scan, and a second blood sample on days 19-24 of the cycle. Serum progesterone levels of > = 5 mmol/L in days 19-24 were used to define the 225 subjects with ovulatory menstrual cycles, whose data are the subject of the analyses shown here. Results: SHBG was positively associated with percent water in both follicular and luteal phases of the menstrual cycle. Total and free estradiol and total and free testosterone were not associated with percent water in the follicular phase, but in young women with ovulatory cycles, were all negatively associated with percent water in the luteal phase. Conclusions: Our results from young women aged 15-30 years add to the evidence that the extent of fibroglandular tissue in the breast that is reflected in both mammographic density and breast water is associated positively with higher serum levels of SHBG, but not with higher levels of sex hormones

Mammographic features associated with interval breast cancers in screening programs

Abstract Introduction Percent mammographic density (PMD) is associated with an increased risk of interval breast cancer in screening programs, as are younger age, pre-menopausal status, lower body mass index and hormone therapy. These factors are also associated with variations in PMD. We have examined whether these variables influence the relative frequency of interval and screen-detected breast cancer, independently or through their associations with PMD. We also examined the association of tumor size with PMD and dense and non-dense areas in screen-detected and interval breast cancers. Methods We used data from three case-control studies nested in screened populations. Interval breast cancer was defined as invasive breast cancer detected within 12 months of a negative mammogram. We used a computer-assisted method of measuring the dense and total areas of breast tissue in the first (baseline) mammogram taken at entry to screening programs and calculated the non-dense area and PMD. We compared these mammographic features, and other risk factors at baseline, in women with screen-detected (n?=?718) and interval breast cancer (n?=?125). Results In multi-variable analysis, the baseline characteristics of younger age, greater dense area and smaller non-dense mammographic area were significantly associated with interval breast cancer compared to screen-detected breast cancer. Compared to screen-detected breast cancers, interval cancers had a larger maximum tumor diameter within each mammographic measure. Conclusions Age and the dense and non-dense areas in the baseline mammogram were independently associated with interval breast cancers in screening programs. These results suggest that decreased detection of cancers caused by the area of dense tissue, and more rapid growth associated with a smaller non-dense area, may both contribute to risk of interval breast cancer. Tailoring screening to individual mammographic characteristics at baseline may reduce the number of interval cancers