Clinical Risk Profile Research Articles

RET C611Y Germline Variant in Multiple Endocrine Neoplasia Type 2A in Denmark 1930–2021: A Nationwide Study

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare hereditary cancer syndrome caused by pathogenic variants in the rearranged during transfection (RET) gene and is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), primary hyperparathyroidism (PHPT), cutaneous lichen amyloidosis (CLA), and Hirschsprung’s disease. Phenotypic data on the RET C611Y variant remain sparse. Consequently, we aimed to establish a clinical risk profile. Methods: We conducted a nationwide study of all cases (n = 128) born after 1 January 1930 and recognized as carrying the RET C611Y variant in Denmark before 1 April 2021. Results: The median follow-up after birth was 47 years (range, 3–92). Age-related penetrance at age 70 years for MTC was 98% (CI, 91–100), for PHEO 24% (CI, 16–37), and for PHPT 10% (CI, 5–20). None had CLA or Hirschsprung’s disease. The age-related progression of MTC was significant (p < 0.001). The median age at T0N0M0 was 11 years (2–62), at T1-4N0M0 was 37 years (12–65), at TxN1M0 was 47 years (16–79), and at TxNxM1 was 50 years (28–70). At the last follow-up, 56% of thyroidectomized cases (n = 103) were biochemically cured. Overall survival at 70 years was 74% (CI, 59–84). Conclusions: RET C611Y is associated with a very high penetrance of MTC and a low penetrance of PHEO and PHPT. CLA and Hirschsprung’s disease almost never occur. MTC seems moderately aggressive, but large variability can be seen. Overall survival may be comparable to that of the general population.

DOP104 International differences in pre-operative characteristics and postoperative management in patients with Crohn’s disease following ileocolic resection: a report from the IMPACT consortium

Abstract Background Intestinal surgery is a key treatment for Crohn’s disease (CD). Large cohort data on perioperative management are vital to improve postoperative outcomes. This study aimed to assess and compare preoperative characteristics and postoperative management across three large prospective cohort studies of CD patients following ileocolic resection (ICR). Methods The IMPACT consortium (International Multidisciplinary Research Collaboration on Postoperative IBD) is an intercontinental initiative focused on postoperative inflammatory bowel disease research. Prospective data were used from three ongoing cohort studies with a comparable set-up and data collection, including CD patients who underwent ICR between December 2009 and September 2024, originating from the Netherlands (NL), North-America (Canada [CAN] and United States of America [USA]) and France (FR). Pre-operative characteristics, clinical risk profiles for post-operative recurrence (POR), use of postoperative prophylactic medication and performance of endoscopic evaluation were compared between the involved countries. Results 1,601 patients with CD following ICR were included (455 NL, 149 CAN, 307 USA, 690 FR)(48.3% male; median age at surgery 33.7 years [IQR 25.8-46.6])(Table 1). Active smoking rates were higher in Europe (NL: 26.2%; FR: 32.8%) compared with North America (CAN: 13.2%; USA: 8.2%). Prior small bowel resections were more common in North American (CAN: 29.5%; USA: 27.0%) compared with Europe (NL: 20.0%; FR: 17.0%). Preoperative biological exposure was lower in Canada (55.7%) and the USA (56.0%) compared with the Netherlands (69.2%) and France (75.5%). A higher proportion of Dutch patients had non-complicated CD (Montreal B1) at surgery (18.4%) compared to other countries (CAN: 1.4%; USA: 2.3%; FR: 4.5%). Overall, 72.7% were considered high-risk for POR, with the lowest rates in the Dutch cohort (62.2%) compared to the other countries (CAN: 73.8%; USA: 77.9%; FR: 77.1%). Postoperative prophylactic medication was initiated in 42.2% with higher rates in the USA (45.9%) and France (51.0%) compared with the Netherlands (28.5%) and Canada (34.9%). Details on postoperative prophylactic medication use are provided in Table 2. An endoscopic evaluation within one year postoperatively was performed in 89.0% of patients, with higher rates (>85%) in the Netherlands, Canada, and France, compared with the USA (66.9%). Conclusion This first study of the IMPACT consortium revealed notable differences in preoperative characteristics, risk profiles for postoperative recurrence, use of prophylactic medication, and postoperative endoscopic evaluation across Europe and North America. Further analyses will include the assessment of rates and factors associated with endoscopic recurrence.

Nomogram for predicting early shoulder joint dysfunction after breast cancer surgery

AbstractObjectiveThis study aims to construct a clinical risk profile nomogram model for predicting early shoulder joint dysfunction (SJD) after breast cancer surgery.MethodsUsing a convenience sampling method, the clinical data of 161 breast cancer patients between February 2022 and July 2023 at Affiliated Cancer Hospital of Nanjing Medical University were selected and analyzed retrospectively. Risk factors were identified using univariate and multivariate logistic regression analyses. The R software was used to construct the risk prediction model and to plot the nomogram for early SJD post‐breast cancer surgery. The model's predictive performance was evaluated using the receiver operating characteristic (ROC) curve and the Hosmer–Lemeshow test.ResultsAmong the 161 patients, 104 (64.6%) experienced SJD. Multivariate logistic regression analysis finally included the functional exercise compliance scale for postoperative breast cancer patients (FECSPBCP), the compliance scale of physical exercise, the body mass index of patients, involved side to‐hand dominance, and the operation mode of breast and lymph nodes into the model. The area under the ROC curve (AUC) was 0.785 (95% confidence interval: 0.711–0.860), indicating a good model fit as confirmed by the Hosmer–Lemeshow test (X2 = 3.2891, p = .9149). Internal validation using the Bootstrap resampling method (n = 1000) yielded an AUC of 0.731.ConclusionsThe incidence of early SJD was high among postoperative breast cancer patients. The constructed risk prediction model can assist medical professionals in the early identification of high‐risk individuals and provide targeted interventions to prevent long‐term disabilities.

Complex interactions and composite burden of risk factors in vascular cognitive impairment.

Vascular cognitive impairment (VCI) stresses the vascular contributions to cognitive decline, ranging from mild to major forms. Except for symptomatic treatment for relevant vascular diseases, the other recommended strategy is to intervene in key vascular risk factors (VRFs) as early as possible. A considerable amount of previous research delineated the association of a specific factor with dementia, involving each risk factor discussed in the present review. However, due to the heterogeneity and complexity of VCI, managing a single factor is insufficient to reduce its incidence and prevalence. Ongoing studies suggest differences in the impact of various combinations of risk factors on dementia. Here in this review, we aimed to provide an updated overview of clinical evidence and implications of complex interactions among various risk factors of VCI, including common VRFs and modifiable dementia-related risk factors. Understating the effect of comorbid risk factors on VCI and underlying mechanisms of them during VCI progression is essential for identifying high-risk population and developing preventive strategies. Furthermore, we summarized common composite risk scores and models used for risk evaluation and prediction of VCI, involving conventional risk scores, subclinical vascular composites, and novel risk models driven by intelligent algorithms. Lastly, we discussed potential gaps and research directions on searching specific clinical risk profiles, constructing effective risk scores, and implementing targeted risk interventions.

Artificial intelligence-derived coronary artery calcium scoring saves time and achieves close to radiologist-level accuracy accuracy on routine ECG-gated CT.

Artificial Intelligence (AI) has been proposed to improve workflow for coronary artery calcium scoring (CACS), but simultaneous demonstration of improved efficiency, accuracy, and clinical stability have not been demonstrated. 148 sequential patients who underwent routine calcium-scoring computed tomography were retrospectively evaluated using a previously validated AI model (syngo. CT CaScoring VB60, Siemens Healthineers, Forscheim, Germany). CACS was performed by manual (Expert alone), semi-automatic (AI + expert review), and automatic (AI alone) methods. Time to complete and intraclass correlation coefficients were the primary endpoints. Secondary endpoints included differences in multiethnic study of atherosclerosis (MESA) percentiles and stratification by calcium severity. AI and expert CACS agreement was excellent (ICC = 0.951; 95% CI 0.933-0.964). The global median time was 15 ± 2s for AI ("Automatic"), 38 ± 13s for the AI + manual review ("Semiautomatic") and 45 ± 24s for the manual segmentation. Automatic segmentation was faster than manual segmentation for all CACS severities (P < 0.001). AI computational time was independent of calcium burden. Global mean bias in Agatston score across all patients was 7.4 ± 102.6. The mean bias for global MESA score percentile was 2.1% ± 12%. 95% of error corresponded to a ± 10% difference in MESA score. The use of AI for CACS performs excellent accuracy, saves approximately 60% of time in comparison to manual review, and demonstrates low bias for clinical risk profiles. Time benefits are magnified for patients with high CACS. However, a semi-automatic approach is still recommended to minimize potential errors while maintaining efficiency.

Phenome-wide diagnostic comparison among suicide deaths and living individuals with chronic pain diagnoses

BackgroundChronic pain, regardless of its type, is a significant risk factor for suicide. However, not all individuals with chronic pain also experience suicidal thoughts and behaviors. Better characterization of clinical risk profiles and comorbidities across the medical spectrum among people with chronic pain who die by suicide is urgently needed to aid treatment and prevention strategies.MethodsThis case–control study leverages population-based data from the Utah Suicide Mortality Risk Study. Specifically, we identify clinical phenotypes from diagnostic data that differentiate between individuals that died by suicide with chronic pain diagnoses (N = 1,410) and living control individuals who also had chronic pain diagnoses (N = 4,664). Medical diagnostic codes were aggregated via phecodes to perform a phenotype-based phenome-wide association study. Using multivariable logistic regression analysis adjusting for covariates and multiple testing, differences in 1,727 common clinical phenotypes (phecodes) were assessed between suicide deaths and controls with chronic pain diagnoses. Models were also stratified by sex.ResultsChronic pain diagnoses were nearly three times more prevalent in individuals who died by suicide compared with those who did not. Sixty-five phecodes were significantly overrepresented among suicide deaths with chronic pain diagnoses compared with controls with chronic pain diagnoses. Utah suicide deaths with chronic pain had significantly more psychiatric diagnoses (mood disorders, anxiety disorders, attention deficit hyperactivity disorder, posttraumatic stress disorder, personality disorders, schizophrenia/psychosis, substance use related traits and prior overdoses, and diagnoses related to previous suicidal thoughts and behaviors) in addition to insomnia and specific pain related diagnoses compared to Utah controls with chronic pain (odds ratios ranged from 1.40–7.10). Twenty-five phecodes were overrepresented in controls with chronic pain compared to suicides. These were related to preventative care, cancer, obesity and other conditions (odds ratios ranged from 0.16–0.73). Sex-specific analyses largely replicated the combined analyses, yet the strength of the association was stronger for women with phecodes related to prior self-harm.ConclusionsResults identified multiple clinical comorbidities with chronic pain that differentiate suicide deaths from living control individuals with a history of diagnosed chronic pain. Our findings may help discern individuals with chronic pain who may be at greater risk for suicide death.

Clinical Correlates of a Single-item Physical Activity Questionnaire among Patients Undergoing Stress SPECT Myocardial Perfusion Imaging

BackgroundThere has been an increasing call for employing ultrashort exercise activity questionnaires as a clinical “vital sign”. To-date, this has not been applied to patients undergoing cardiac stress testing. MethodsWe evaluated 1,136 patients who completed a one-item exercise questionnaire before undergoing stress SPECT myocardial perfusion imaging (MPI). This question asked patients to grade how much they exercise during daily life on an 11-point scale (0= none, 10 = always). Patients were divided into four exercise activity groups based on their response: no, low, moderate, and high exercise activity. The results of this questionnaire were compared to patients clinical risk profile, mode of stress testing (exercise versus pharmacologic), and exercise treadmill duration. ResultsWe noted a stepwise inverse relationship between exercise activity and patients’ frequency of hypertension, diabetes, and obesity (p<0.001 for each). Patients with no reported exercise activity were more likely to complain of dyspnea. There was a stepwise increase in the number of patients performing treadmill exercise with increasing reported exercise activity (p<0.001). The duration on treadmill exercise increased in stepwise fashion with higher patient reported exercise activity (p<0.001). ConclusionOur single-item, self-reported questionnaire was correlated to patients’ risk profiles, their mode of stress testing, and cardiorespiratory fitness. These correlates, along with the pragmatic nature of this ultrashort questionnaire, and its built-in identification of patients who may warrant exercise counseling, augurs for adopting ultrashort questionnaires regarding exercise activity among patients undergoing stress MPI and other cardiac imaging tests where functional capacity is not routinely assessed.

Severe aortic stenosis is associated with left atrial prothrombotic flow changes that persists despite successful aortic valve replacement

Abstract Background Severe aortic stenosis (AS) is associated with ischaemic stroke independently of atrial fibrillation (AF) or other causes. Even after aortic valve replacement (AVR), patients remain affected by up to 15% five-year rate of incident ischaemic strokes independently of AVR-related complications and with knowledge gaps in the underlying pathophysiology. Purpose To assess whether severe AS leads to prothrombotic left atrial (LA) flow changes with reduction of LA velocities and vorticity which do not normalise after AVR. Methods Seventy-seven participants without history of AF were recruited in this study: N=40 with severe AS (60% male; age 73 ±10 years, BMI 28 ±5 Kg/m2, median CHA2DS2VASc = 3) and N=37 controls with similar clinical risk profile (51% male; age 71 ±6 years, BMI 28 ±5 Kg/m2, median CHA2DS2VASc = 3). All participants underwent a cardiovascular magnetic resonance (CMR) scan to quantify left ventricular (LV) volumes, mass, and ejection fraction (LVEF), LV global longitudinal strain (GLS) as a sensitive marker of longitudinal dysfunction, LA maximum volume and emptying fraction (LAEF), LA blood flow peak velocity and vorticity by 4-dimensional flow CMR. Out of the 40 patients with severe AS, N=23 (58%) underwent a successful AVR and were followed-up with a repeat CMR scan at approximately 6 months after surgery. Results When compared to matched controls, patients with severe AS displayed significantly higher LV mass, smaller LA and LV volumes (i.e. concentric LV hypertrophy), significantly reduced GLS but higher (more hyperdynamic) LVEF (all p&amp;lt;0.05), as expected. LAEF (i.e. global LA function) was not significantly different from controls but despite this, severe AS was associated with slightly lower LA peak flow velocity (mean 0.25 vs. 0.28 m/sec respectively) and lower LA flow vorticity (mean 16.6 vs. 21.1 radians) compared to controls (both p&amp;lt;0.05). Successful AVR led to complete regression of LV hypertrophy (p&amp;lt;0.05) with LV mass that was no longer different from controls (p&amp;gt;0.05). Nevertheless, post-AVR patients displayed a persistent adverse morpho-functional phenotype characterised by persistently smaller LA and LV volumes, persistently hyperdynamic LV function with reduced GLS (all p&amp;lt;0.05), as well as adverse LA flow changes with significantly lower velocity (mean 0.24 vs 0.28 m/sec, p=0.003) and vorticity when compared to controls (17.1 vs 21.1 radians, p&amp;lt;0.001). Conclusions Patients with severe AS display adverse LA physiology and structure (prothrombotic LA flow characteristics in smaller LA size) and LV changes (smaller size with reduced longitudinal function and hyperdynamic function), which persist after successful AVR despite normalisation of the LV hypertrophy.Figure 1

Risk factors for infectious endocarditis of prosthetic valves: a systematic review

Introduction: valve endocarditis is a major health challenge; its etiology is varied, and it can cause multiple complications or death.Objective: to identify risk factors for infective endocarditis in prosthetic valves. Methods: systematic and retrospective review of the available literature using records from Pubmed, Epistemonikos, Cochrane library, Uptodate.Results: in Argentina, from September 2013 to March 2016, 502 patients with infective endocarditis (IE) were studied in 48 medical centers. The majority were men (69,9 %) with a mean age of 60,7 years. The main risk factors were known underlying heart disease (45,36 %), diabetes (23,5 %), chronic renal failure (16,5 %), neoplastic disease (12,1 %) and history of previous IE (8,96 %). The most frequent predisposing events were endovascular (31,9 %) and dental (12,6 %) procedures. New causes of IE related to gastrointestinal pathologies were also identified.Conclusion: patients with IE have a high clinical risk profile and show increasing age over the decades. Staphylococcus aureus is the most frequent microorganism followed by Streptococcus viridans. The identification of independent predictors of in-hospital mortality continues to be a challenge due to the new agents that are identified or risk factors that are added over time; identifying them could help to establish behavioral modification strategies that lead to improved outcomes

To Evaluate Efficiency of Various Coronary Artery Disease Risk Scores With Traditional Risk Factors in Patients Undergoing Coronary Angiography.

To analyze and compare various cardiovascular disease risk scores in Western Indian patients undergoing Coronary angiogram (CAG). In this prospective cross-sectional study, 1213 patients who underwent conventional coronary angiography; clinical risk profile and biochemical investigations were evaluated prior to undergoing CAG. Apart from the demographic information, 10-year absolute risk of having a major cardiovascular event (cardiovascular death, myocardial infarction or stroke) was calculated for each patient using various available Traditional Risk Scores (TRS). The population was divided in low, intermediate and high-risk categories for each of these scores. Traditional cardiovascular risk factors like hypertension (41.8%) and diabetes mellitus-II (26.9%) were the two most prevalent risk factors in our study population. A higher risk value for all these TRS was more likely to be associated with obstructive coronary artery disease (OCAD) on CAG. Patients with high risk (≥20% for 10-year) QRESEARCH (QRISK3) score category had higher number of patients with obstructive CAD (49.6%) as compared to high risk category of risk score for those with high Global Registry of Acute Coronary Events (GRACE) score (46.6%) or risk Framingham (FRS CHD) score (29.2%) and risk atherosclerotic cardiovascular disease (ASCVD) score (30.1%) (P < 0.0001). A higher TRS was more likely to be associated with obstructive CAD, with the highest predictability being with QRISK3 (QRISK3 score 60.9%, GRACE score 54.9%, FRS-CHD score 34% and ASCVD score 42.1% respectively; P < 0.0001). A substantial study population (27.4%) cannot be identified using any of these TRS and hence a need of indigenous or modified risk scores is proposed. QRISK3 score was most efficacious for predicting obstructive CAD in our Indian study population on CAG. A higher risk score also correlated with the number of vessels involved on coronary angiogram. A substantial obstructive CAD patient could not be identified using traditional risk scores hence need for an indigenous or modified score.

Alternative Payment Models and Performance in Federally Qualified Health Centers

ImportanceSeveral state Medicaid agencies have transitioned from traditional fee-for-service to a value-centric alternative payment model (APM) to reimburse federally qualified health centers (FQHCs). Little is known about the effects of this shift on FQHC performance.ObjectiveTo assess the association between APMs and the clinical performance, payer mix, risk profile, and financial sustainability of FQHCs.Design, Setting, and ParticipantsThis retrospective cohort study was performed in 684 FQHCs (representing 37 states plus the District of Columbia) that continuously operated between January 2009 and December 2021. Data on payer mix (eg, type of insurance) and risk profile (eg, proportion of patients with chronic conditions) of FQHC patients were obtained from the Uniform Data System, and clinic-level financial data (eg, revenue) were obtained from Internal Revenue Service form 990 tax documents. Data were analyzed between November 2022 and October 2023.ExposureInitial rollout of a value-based payment model (ie, an APM) for FQHCs, as offered by state Medicaid program, between January 2013 and December 2021.Main Outcomes and MeasuresThe main outcomes were 4 audited process measures of health care quality (cervical and colorectal cancer screening and body mass index [BMI] assessment for adults and children) and 2 intermediate health outcome measures (hypertension control and diabetes control). A difference-in-differences design was used with staggered implementation comparing FQHCs before and after the initial APM rollout vs contemporaneous changes in FQHCs in states without APMs.ResultsA total of 684 FQHCs (8892 FQHC-years) that served 17 823 959 patients in 2021 (57.3% female) were included in the study. Among FQHCs in states implementing APMs, significant differential increases in 3 of the 4 process quality measures were observed compared with FQHCs in states that did not implement an APM: colorectal cancer screening (3.24 percentage points [pp]; 95% CI, 1.40-5.08 pp), adult BMI (3.19 pp; 95% CI, 0.70-5.68 pp), and child BMI (4.50 pp; 95% CI, 1.83-7.17 pp). There were also modest differential improvements in blood pressure control for individuals with hypertension (1.02 pp; 95% CI, 0.04-2.00 pp) and blood glucose control for individuals with type 2 diabetes (1.02 pp; 95% CI, 0.02-2.02 pp) compared with FQHCs in states without an APM. There was no evidence that the APM rollout was associated with clinics selecting healthier patients (–0.01 pp; 95% CI, –0.21 to 0.19 pp) or stinting on care (–0.02 visits; 95% CI, –0.08 to 0.04 visits).Conclusions and RelevanceIn this cohort study, introduction of Medicaid APM options for FQHCs was associated with modest, statistically significant increases in quality concentrated among FQHCs with APM models that explicitly incentivized quality. This finding suggests that APMs can be both a financially viable and a health-promoting model for reimbursement in the health care safety net.

Economic Disparities in Utilization and Outcomes of Structural Heart Disease Interventions in the United States

BackgroundDisparities in access to care cause negative health consequences for underserved populations. Economic disparities in structural heart disease (SHD) interventions are not well characterized. ObjectivesThe objective of this study was to evaluate economic disparities in the utilization and outcomes of SHD interventions in the United States. MethodsWe queried the National Inpatient Sample (2016-2020) to examine economic disparities in the utilization, in-hospital outcomes, length of stay, and cost of SHD interventions among patients ≥65 years of age. Outcomes were determined using logistic regression models. ResultsA total of 401,005 weighted hospitalizations for transcatheter aortic valve replacement, left atrial appendage occlusion, transcatheter mitral valve repair, and transcatheter mitral valve replacement were included. Utilization rates (number of procedures performed per 100,000 hospitalizations) were higher in patients with high income compared with medium and low income for transcatheter aortic valve replacement (559 vs 456 vs 338), left atrial appendage occlusion (148 vs 136 vs 99), transcatheter mitral valve repair (65 vs 54 vs 41), and transcatheter mitral valve replacement (7.7 vs 6.7 vs 1.2) (all P < 0.01). Low- and medium-income patients had distinctive demographic and clinical risk profiles compared with high-income patients. There were no significant differences in the adjusted in-hospital mortality, key complications, or length of stay between high-, medium-, and low-income patients following any of the 4 SHD interventions. High-income patients incurred a modestly higher cost with any of the 4 SHD interventions compared with medium- and low-income patients. ConclusionsEconomic disparities exist in the utilization of SHD interventions in the United States. Nonetheless, adjusted in-hospital outcomes were comparable among high-, medium-, and low-income patients. Multifaceted implementation strategies are needed to attenuate these utilization disparities.

Navigating ethical challenges of integrating genomic medicine into clinical practice: Maximising beneficence in precision oncology

The development of gene expression profiling and next-generation sequencing technologies have steered oncogenomics to the forefront of precision medicine. This created a need for harmonious cooperation between clinicians and researchers to increase access to precision oncology, despite multiple implementation challenges being encountered. The aim is to apply personalised treatment strategies early in cancer management, targeting tumour subtypes and actionable gene variants within the individual’s broader clinical risk profile and wellbeing. A knowledge-generating database linked to the South African Medical Research Council’s Genomic Centre has been created for the application of personalised medicine, using an integrated service and research approach. Insights gained from patient experiences related to tumour heterogeneity, access to targeted therapies and incidental findings of pathogenic germline variants in tumour DNA, provided practice-changing evidence for the implementation of a cost-minimisation pathology-supported genetic testing strategy. Integrating clinical care with genomic research through data sharing advances personalised medicine and maximises precision oncology benefits.

International consensus on mitotane treatment in pediatric patients with adrenal cortical tumors: indications, therapy, and management of adverse effects.

Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects. A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements. We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required. The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.

Comparison of risk profiles of participants in the Women's IschemiA TRial to Reduce events In non-ObstRuctive CAD (WARRIOR) trial, using Coronary Computed Tomography Angiography vs Invasive Coronary Angiography

ObjectiveTo compare baseline characteristics of participants in the Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR) trial by qualification by Coronary Computed Tomography Angiography (CCTA) or Invasive Coronary Angiography (ICA). MethodsThe WARRIOR trial (NCT03417388) is an ongoing multicenter, prospective, randomized, blinded outcome evaluation of intensive medical therapy vs. usual care in women with suspected Ischemia and No Obstructive Coronary Artery Disease (INOCA) identified by either CCTA or ICA on the outcome of major adverse cardiovascular events (MACE). No obstructive coronary artery disease is defined as <50% luminal stenosis and normal coronary arteries is defined as no evidence of atherosclerosis including calcified and non-calcified plaque. Data presented was extracted on May 27, 2020. No clinical outcomes were assessed. ResultsAn initial sample cohort of 797 women was included. The majority were younger than 65 years, White participants (73.3%), 159 had diabetes (19.9%), and 676 had angina (84.8%) with the remainder having symptoms of suspected ischemic heart disease. Over 50% of randomized participants had normal coronaries without luminal irregularities by ICA or CCTA. Participants randomized to ICA were more likely to have worse baseline clinical risk profiles with older age, higher burden of cardiac risk factors and poor quality of life with disabling angina. ConclusionsAmong this initial sample of women with suspected INOCA randomized in the WARRIOR trial, there is a differential baseline cardiac risk of participants enrolled after CCTA or ICA. However, the majority had no evidence of atherosclerotic plaque or obstructive stenosis, after evaluation by ICA or CCTA. These results suggest that non-invasive evaluation with CCTA is likely to be associated with lower risk of MACE.

Recurrence of Clostridioides difficile infection and mortality in older inpatients.

The prevalence of Clostridioides difficile infection in older and frail population is extremely high and adverse outcomes, including future recurrences and premature mortality, are common. Nonetheless, the clinical risk profile for Clostridioides difficile recurrence in older people is still controversial. We aimed to investigate: 1) the association between Clostridioides difficile recurrence and 6-month mortality; 2) the risk factors for Clostridioides difficile recurrence after hospital discharge. This is a retrospective study on adults with a first episode of Clostridioides difficile infection admitted to all Internal Medicine and Geriatrics Units of the University Hospital of Ferrara (Italy) between January 2018 and December 2020. For each patient, sociodemographic, clinical and laboratory data were collected through hospital database system. The primary and secondary outcomes were mortality and recurrence within 6months from the first infectious episode, respectively. The mean age of the 386 enrolled patients was 77.8years; 61.7% were females. Twelve percent patients had Clostridioides difficile recurrence and 32.1% patients died during the 6-month follow-up. At Cox analysis, after adjustment for the potential confounders, participants with recurrence reported a twofold risk of death compared to those without recurrence (HR, 95% CI 2.45, 1.59-3.78). Compared to patients treated with metronidazole, those treated with vancomycin showed a lower risk of recurrence (log-rank p < 0.001). Clostridioides difficile recurrence is associated with a higher risk of mortality and it may itself be a marker of frailty and vulnerability. Vancomycin treatment during the infectious episode was associated with lower recurrence rate, as compared to metronidazole.

Predictors of planned home birth before and during the COVID-19 pandemic.

To determine how demographic and clinical predictors of home birth have changed since the onset of the COVID-19 pandemic in the US. Using National Vital Statistics birth certificate data, a retrospective population-based cohort study was performed with planned home births and hospital births among women age≥18 years during calendar years 2019 (pre-pandemic) and 2021 (pandemic-era). Birth location (planned home birth vs. hospital birth) was analyzed using univariate and multivariable logistic regression, systematically examining the interaction of each demographic and clinical covariate with study year. After exclusions, a total of 6,087,768 birth records were retained for analysis, with the proportion of home births increasing from 0.82 % in 2019 to 1.24 % in 2021 (p<0.001). In the final multivariable logistic regression model of planned home birth, five demographic variables retained a statistically significant interaction with year: race and ethnicity, age, educational attainment, parity, and WIC participation. In each case, demographic differences between those having planned home births and hospital births became smaller (odds ratios closer to 1) in 2021 compared to 2019. Planned home births increased by more than 50 % during the pandemic, with greater socioeconomic diversity in the pandemic-era home birth cohort. The presence of clinical risk factors remained a strong predictor of hospital birth, with no evidence that pandemic-era home births had a higher clinical risk profile as compared to the pre-pandemic period.

Early-Staged Carotid Artery Stenting Prior to Coronary Artery Bypass Grafting: Analysis of the Early and Mid-Term Results in Comparison with a Consecutive Cohort of Isolated Coronary Artery Surgery Patients.

The aim of the present study was to analyze retrospectively the results of patients who underwent early-staged, i.e., within 24-48 h, carotid artery stenting (e-s CAS) before coronary artery bypass grafting (CABG). Between December 2014 and December 2022, 1046 consecutive patients underwent CABG; 31 of these patients (3%) were subjected to e-s CAS prior to CABG (e-s CAS + CABG group). Preoperative and intraoperative variables and early and mid-term results of the e-s CAS + CABG group were compared with those of patients who underwent isolated CABG (CABG group). As compared with the CABG group, the e-s CAS + CABG group showed a worse clinical risk profile due to higher Euroscore-2 values and incidence of obstructive pulmonary disease and bilateral carotid artery and peripheral artery diseases (p < 0.05, for all comparisons). The combined end point of operative mortality, periprocedural myocardial infarction, and stroke was 3.2% (0%/0%/3.2%) in the e-s CAS + CABG group vs. 5.9% (2.2%/2.8%/0.9%) in the CABG group (p > 0.5, for all measurements). At 5 years, actuarial survival was 74% ± 16% in the e-s CAS + CABG group vs. 93% ± 4.0% in the CABG group, freedom from cardiac death was 100% vs. 98% ± 1.0% (p = 0.6), and freedom from MACCEs was 85% ± 15% vs. 97% ± 2.5% (p > 0.1, for all comparisons). Independent predictors of all-causes death were advanced age at the operation (p < 0.0001), a lower value for left ventricular ejection fraction (p = 0.05), and a high Euroscore-2 (p = 0.04). CABG preceded by e-s CAS appears to be associated with satisfactory early outcomes while limiting the risk of myocardial infarction to a very short time interval between the two procedures. Freedom from late all-causes death, cardiac death, and MACCEs were comparable and equally satisfactory, underscoring the positive protective effects of CAS and CABG on the carotid and coronary territories over time.

Association Between Remnant Cholesterol and Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography and/or Percutaneous Coronary Intervention.

Contrast-induced nephropathy (CIN) is an acute renal complication that can occur after the use of iodinated contrast media. Remnant cholesterol (RC) is one of the markers of atherosclerotic cardiovascular disease risk. We evaluated the impact of RC on CIN and clinical outcomes after coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). Consecutive patients (n = 3332) undergoing CAG and/or PCI were assessed in this retrospective study. Patients were divided into four groups based on baseline RC levels. In the quartile analysis, RC were associated with a higher risk of CIN, especially when RC ≤0.20 or ≥0.38mmol/L (P < .05). However, after adjustment, the association of RC with CIN was not significant. There was a significant correlation between RC and repeated revascularization in patients undergoing PCI (P < .001) and driven primarily by the highest quartile level. After adjustment, this remained statistically significant (adjusted odds ratio (aOR) 4.06; 95% CI 2.10-7.87; P < .001). This is the first large study to show a possible association between RC and the risk of CIN after CAG and/or PCI; however, this finding was not further confirmed after adjustment. The complex clinical risk profile of patients, rather than RC itself, may contribute to the risk of CIN in this high-risk subgroup.

Contrasting Risk Profile in Idiopathic Inflammatory Myopathy (IIM) Patients with Cancer Before and After IIM Diagnosis

Background: Patients with adult-onset idiopathic inflammatory myopathy (IIM) were at risk of cancer. While the recently published international guideline on cancer screening suggested cancer risk stratification in patients with newly diagnosed IIM, the difference in clinical and serological risk profile among patients with cancer diagnosed before and after IIM diagnosis remained uncertain. Methods: MyoHK was a longitudinal observational cohort that collected data from patients with rheumatologist diagnosis of IIM from 8 rheumatology centres in Hong Kong. Data were reviewed from 2004-2023 for this study. Patients with unavailable myositis specific antibody (MSA) were excluded from analysis. Occurrence of cancer 3 years before to 3 years after the diagnosis of IIM were documented. Patients with active cancer 3 years before diagnosis of IIM were classified to “Prior cancer” group and patients with cancer diagnosed at or within 3 years after IIM diagnosis were classified to “subsequent cancer” group. Patients were stratified to high, intermediate and standard cancer risks. Risk profile between the “prior cancer” and “subsequent cancer” groups were compared. Results: 501 patients were included in analysis. 82 patients had cancer within 3 years, in which 21 patients (25.6%) had cancer within 3 years preceding IIM diagnosis and 61 patients (74.4%) developed cancer at or within 3 years after IIM diagnosis. Nasopharyngeal, lung and breast cancers accounted for the top 3 cancers in both groups. In the “Prior cancer” group, patients were more likely to be female (85.7% vs 55.7%, p = 0.014) and were MSA-negative (33.3% vs 9.8%, p = 0.011). No patient in the “Prior cancer” group developed interstitial lung disease (0% vs 18.0%, p = 0.037) or fulfilled criteria for anti-synthetase syndrome (0% vs 13.1%, p = 0.062). Anti-TIF1g antibody was the most identified MSA in the two groups (42.9% vs 54.1%, p = 374). Myositis-associated-antibody (14.3% vs 42.6%, p = 0.019) and anti-Ro52 antibody (14.3% vs 37.7%, p = 0.047) were more common in the “subsequent cancer” group. In the overall cohort, 228 (45.5%), 246 (49.1%) and 27 (5.4%) of IIM patients were stratified into high, intermediate and standard cancer risk. Two-thirds of the “Prior cancer” group were stratified into high-risk while the remaining one-third being intermediate-risk, compared to 73.8% (p = 0.532) and 26.2% (p = 0.532) in the “subsequent cancer” group. Mortality between the two groups were comparable (38.1% vs 42.6%, p = 0.716). Conclusion: Compared to IIM patients with cancer detected at or after IIM diagnosis, patients with prior cancer were more likely to be female, negative for MSA and absence for ILD.