Aid Risk Stratification Research Articles

New echocardiographic indices of shift to biventricular failure to optimize risk stratification of chronic heart failure.

AimsThe present study investigated the prognostic impact of either isolated left atrial (LA) impairment, or its association with right ventricular (RV) failure, in heart failure (HF) with reduced ejection fraction (HFrEF), using basic and speckle tracking echocardiography (STE).Methods and resultsOne hundred and six outpatients with HFrEF were enrolled in this prospective observational study. Patients with primary lung diseases, non‐sinus rhythm, previous cardiac surgery, and poor acoustic window were excluded. After clinical examination and basic echocardiography, STE was used to measure peak atrial longitudinal strain (PALS) and a new marker of RV performance and pulmonary circulation relation: free‐wall RV longitudinal strain (fwRVLS)/systolic pulmonary artery pressure (sPAP). Patients were followed for all‐cause/cardiovascular death and HF hospitalization. Of 84 eligible patients (60.1 ± 11.5 years; 82% male patients), 48 reached the combined endpoint (cardiovascular death and/or HF hospitalization). Population was divided into three groups: Group 1 (PALS ≥ 15 and fwRVLS/sPAP ≤ −0.5), Group 2 (PALS ≤ 15 and fwRVLS/sPAP ≤ −0.5), and Group 3 (PALS ≤ 15 and fwRVLS/sPAP > −0.5). Mean follow up was 3.5 ± 0.3 years. The higher severity groups were associated with higher LA volume index (P < 0.0001), New York Heart Association class (P = 0.02), mitral regurgitation (P = 0.0004) and tricuspid regurgitation grades (P < 0.0001), lower left ventricular (LV) ejection fraction (P = 0.0003), LV global longitudinal strain (P < 0.0001), PALS (P < 0.0001), tricuspid annular plane systolic excursion (P < 0.007), sPAP (P < 0.0001), and RV strain (P < 0.0001). Reduced PALS and fwRVLS/sPAP were independent predictors of the combined endpoint with adjusted Cox models (hazard ratio = 9.54; 95% confidence interval = 2.95–30.92; P = 0.0002 for Group 3 vs. Group 1). Kaplan–Meier curves showed early and persistent divergence between the three groups for the prediction of the combined endpoint and of all‐cause death (P < 0.0001).ConclusionsThe combination of LA and right heart damage entails worse prognosis in patients with HFrEF. The evaluation of PALS and fwRVLS/sPAP could aid risk stratification of HFrEF patients to provide them early treatment.

Circulating C-reactive protein levels in patients with suspected obstructive sleep apnea.

To assess determinants of C-reactive protein (CRP) in a cohort of patients referred for investigation of obstructive sleep apnea (OSA) and to determine whether the overlap of OSA and chronic obstructive pulmonary disease (overlap syndrome) is associated with higher levels of CRP. This was a cross-sectional study that included 2,352 patients seen at the West Australian Sleep Disorders Research Institute between 2006 and 2010. All patients had circulating CRP levels measured and spirometry performed. OSA was defined as an apnea-hypopnea index ≥ 5 events/h, and chronic obstructive pulmonary disease was defined as a forced expiratory volume in 1 second/forced vital capacity ratio < 0.70 and age > 40 years. Univariate and multivariate regression analysis were used to identify CRP determinants. The mean age was 51 years (60% male), the median apnea-hypopnea index was 27 events/h, the median 3% oxygen desaturation index was 24 events/h, the mean forced expiratory volume in 1 second was 88% predicted, and the median CRP was 3.0 mg/L. In multivariate analyses, age, body mass index, female sex, neck circumference, apnea-hypopnea index, and desaturation markers (nadir and mean oxygen saturation) were independently associated with higher CRP. Spirometric variables were not predictors. There was no significant difference in CRP among patients with OSA with or without coexisting chronic obstructive pulmonary disease. Markers of OSA severity (apnea-hypopnea index and oxygenation), age, body mass index, neck circumference, and female sex were independent predictors of circulating CRP levels. OSA overlapping with chronic obstructive pulmonary disease was not associated with increased CRP compared to either condition alone, suggesting other mechanisms for the increased cardiovascular disease risk in overlap syndrome. Recognizing factors that predict CRP will help identify patients at higher risk of cardiovascular disease and aid risk stratification. Shah A, Mukherjee S, McArdle N, Singh B, Ayas N. Circulating C-reactive protein levels in patients with suspected obstructive sleep apnea. J Clin Sleep Med. 2022;18(4):993-1001.

The clinical utility of procainamide-induced late potentials on the signal averaged ECG.

Late potentials (LPs) identified on the signal averaged electrocardiogram (SAECG) are a marker for an increased risk of arrhythmias in Brugada syndrome (BrS). Procainamide is a sodium channel blocker used to diagnose BrS. The effects of Procainamide on the SAECG in those with BrS and the significance of Procainamide-induced LPs are unknown. Procainamide provocation was performed for suspected BrS with 12-lead and SAECG pre- and post-infusion. Filtered QRS duration (fQRSd), duration of low amplitude signals<40 μV (LAS40) and root-mean-square voltage in the terminal 40ms (RMS40) were determined. Data from 150 patients were included in the analysis (mean age 44.5 years, 109 males). Procainamide increased fQRSd (Pre 118.8±10.5ms, post 121.2±10.2ms, p<0.001) and LAS40 (Pre 38.7±9.8ms, post 40.2±10.5ms, p=0.005) and decreased RMS40 (Pre 24.6±12ms, post 22.8±12ms, p=0.002). LPs were present in 68/150 (45%) at baseline. Fifteen patients with negative baseline SAECGs had LPs unmasked by Procainamide, but six patients had LPs at baseline that were no longer present following Procainamide. Comparing those with normal hearts (n=48) to those with a final diagnosis of BrS (n=38), Procainamide prolonged fQRSd to a greater extent in those with BrS. Comparing those with Procainamide-induced LPs to those with no LPs at any time did not highlight any aspect of phenotype and did not correlate with a history of ventricular arrhythmias. Procainamide influences the SAECG, provoking LPs in a small proportion of patients. However, there is no evidence that Procainamide-induced LPs provide additional diagnostic information or aid risk stratification.

Maternal Hyperoxygenation Testing in Fetuses with Hypoplastic Left-Heart Syndrome: Association with Postnatal Atrial Septal Restriction

Introduction: In fetuses with hypoplastic left-heart syndrome (HLHS), maternal hyperoxygenation (MHO) may aid risk stratification. We hypothesized that pulmonary vein (Pvein) velocity time integral (VTI) change with MHO would more reliably identify neonates who undergo emergent atrial septoplasty (EAS) than changes in pulmonary arterial pulsatility index (PA PI). Methods: Fetuses with HLHS who underwent MHO testing at our institution between 2014 and 2019 were identified. Data were reviewed in a blinded, retrospective manner. Pvein VTI ratio (prograde:retrograde) was calculated. The primary outcome was neonatal EAS. Results: Twenty-seven HLHS fetuses underwent MHO, and 5 (19%) underwent EAS. Without MHO, a Pvein VTI ratio <3 conferred 60% sensitivity and 100% specificity for EAS. With MHO, a Pvein VTI ratio <6.5 conferred 100% sensitivity and specificity. For an intermediate group of fetuses with a baseline Pvein VTI ratio 3–7, the ratio decrease with MHO conferred 100% sensitivity and specificity. Compared to the Pvein VTI ratio, PA PI was less accurate in identifying EAS neonates. Discussion/Conclusion: Addition of MHO appears to improve the diagnostic ability of the Pvein VTI ratio to identify HLHS fetuses who undergo EAS. The Pvein VTI ratio change may more accurately identify fetuses who undergo EAS than change in PA PI and has less interobserver variability.

A territory-wide study of arrhythmogenic right ventricular cardiomyopathy patients from Hong Kong

Abstract Background Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a hereditary disease characterised by fibrofatty infiltration of the right ventricular myocardium that predisposes affected patients to malignant ventricular arrhythmias, dual-chamber cardiac failure and sudden cardiac death (SCD). Methods This was a territory-wide retrospective cohort study of patients diagnosed with ARVC/D between 1997 and 2019. The primary outcome was incident ventricular tachycardia/ventricular fibrillation (VT/VF). The secondary outcomes were new-onset heart failure with reduced ejection fraction (HFrEF) and all-cause mortality. Results This study consisted of 115 ARVC/D patients (median age: 60 [44.1–70.2] years; 58% male). Of these, 51 and 24 patients developed incident VT/VF and new-onset HFrEF, respectively. Five patients underwent cardiac transplantation, and 14 died during follow-up. Multivariate Cox regression identified prolonged QRS duration as a predictor of VT/VF (P&amp;lt;0.05). Female gender, prolonged QTc duration, the presence of epsilon waves and T-wave inversion (TWI) in any lead except aVR/V1 predicted new-onset HFrEF (P&amp;lt;0.05). Female gender, prolonged QTc duration and the presence of epsilon waves, in addition to the parameters of older age at diagnosis of ARVC/D, prolonged QRS duration and worsening ejection fraction predicted all-cause mortality (p&amp;lt;0.05). Clinical scores were also developed to predict new-onset HFrEF (Table 1a-c) and all-cause mortality (Table 2a-c). This was followed by the application of a non-parametric machine learning survival analysis models for outcome prediction. These machine learning algorithms better capture nonlinear and interactive patterns within survival data compared to traditionally used Cox regression models, which assume the existence of a hazard function between survival data and censored outcomes. The present study introduced weighted random survival forests models for the prediction of incident VT/VF, HFrEF and all-cause mortality. Findings indicate that these machine learning wRSF models performed the best in the prediction of all three aforementioned outcomes compared to other analytical methods. Conclusion Clinical and electrocardiographic parameters are important for assessing prognosis in ARVC/D patients. Machine learning algorithms appear to be the most optimal tools for event prediction, and as such should potentially be used to aid risk stratification and decision-making in the clinical setting. Funding Acknowledgement Type of funding sources: None.

Utility of mutational analysis for risk stratification of indeterminate thyroid nodules in a real-world setting.

American Thyroid Association (ATAn) 2015 guidelines recommend repeat fine-needle aspiration with molecular marker profiling (MMP) or diagnostic lobectomy in thyroid nodules yielding atypia of unknown significance/follicular lesion of unknown significance (AUS/FLUS) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) cytology. Our objective is to describe the molecular profiles and histological correlates of these cytologically indeterminate nodules (CIN) to aid risk stratification. Retrospective chart review. Adults with CIN that underwent MMP from 2017 to 2020. Pearsons' χ2 , Fisher's exact test, nonparametric testing and multiple regression analysis were performed. A total of 89 CIN underwent mutational analysis. Of 55% (n = 49) were Bethesda class III AUS/FLUS and 45% (n = 40) were Bethesda class IV FN/SFN. The US phenotype of a CIN was isoechoic (53%) or hypoechoic (32%) with well-defined margins (98%), absence of calcifications (75%) and mildly increased internal vascularity (70%). A total of 84% and 87% of nodules were classified as mild/moderate or low/intermediate risk per the Thyroid Imaging Reporting and Data System and ATA classifications, respectively. Based on the Thyroseq patient management resource, 6.7% (n = 6) of nodules had a high predicted probability of cancer (≥95%), 41.6% (n = 37) were intermediate probability (40%-94%) and 51.7% (n = 46) were low probability (<40%). MMP revealed positive mutations in 45% (n = 40) of nodules, with 71% demonstrating RAS mutations. Of the nodules that underwent resection (n = 38), 39% (n = 15) had malignant pathology. Increasing the threshold to recommend surgical resection to a Thyroseq predicted probability of cancer to ≥50%, had a 100% sensitivity and 65% specificity for detecting malignant nodules (area under the ROC curve: 0.86). The positive predictive value was 37% and the negative predictive value was 100%. US phenotypes of CIN nodules were variable and did not aid in differentiating malignant from benign nodules. Of the CIN nodules with a positive MMP, most were RAS and had a benign pathology. With the exception of high-risk genetic markers for malignancy, the threshold to recommend surgical resection should be raised for CIN. Further studies to improve risk stratification in these nodules are required.

Prognostic Potential of Heart Rate and Hypertension in Multiple Myeloma Patients.

Background: The prognosis of patients with multiple myeloma (MM) is variable and partly depends on their cardiovascular status. The presence of arrhythmias can lead to worse outcomes. Therefore, this study aimed to evaluate the potential of heart rate (HR) and hypertension in predicating the outcomes of MM patients.Methods: This study retrospectively enrolled patients with MM between January 1, 2010, and December 31, 2018, at the First Affiliated Hospital of Xi'an Jiaotong University. The endpoint was all-cause mortality. The Pearson's chi-square test was used to assess the association between hypertension and outcomes. Univariate and multivariate Cox proportional hazards models were developed to evaluate the relationship between HR and all-cause mortality.Results: A total of 386 patients were included. The mean HR was 83.8 ± 23.1 beats per minute (bpm). Patients with HR >100 bpm had a higher all-cause mortality (79.4%, 50/63) than those with 60 ≤ HR ≤ 100 bpm (39.9%, 110/276) and <60 bpm (19.1%, 9/47) (p < 0.001). Subgroup analysis based on the International Staging System and sex revealed similar relationships (p < 0.01). When stratified by age, patients with HR >100 bpm had higher all-cause mortality than those with a lower HR when age was <65 years or 65–75 years (p < 0.001) but not >75 years. The proportion of patients with hypertension was 54.7% (211/386). However, hypertension was not associated with all-cause mortality in MM patients (χ2=1.729, p > 0.05). MM patients with HR >100 bpm had the highest all-cause mortality.Conclusions: The prognostic potential of HR may be useful in aiding risk stratification and promoting the management of these patients.

Does knowledge of the mutation in hereditary long QT syndrome aid risk stratification?

Does knowledge of the mutation in hereditary long QT syndrome aid risk stratification?

Risk factors for acute kidney injury in critically ill patients with torso injury: A retrospective observational single-center study.

Acute kidney injury (AKI) is common in trauma patients and associated with poor outcomes. Identifying AKI risk factors in trauma patients is important for risk stratification and provision of optimal intensive care unit (ICU) treatment. This study identified AKI risk factors in patients admitted to critical care after sustaining torso injuries.We performed a retrospective chart review involving 380 patients who sustained torso injuries from January 2016 to December 2019. Patients were included if they were aged >15 years, admitted to an ICU, survived for >48 hours, and had thoracic and/or abdominal injuries and no end-stage renal disease. AKI was defined according to the Kidney Disease Improving Global Outcomes definition and staging system. Clinical and laboratory variables were compared between the AKI and non-AKI groups (n = 72 and 308, respectively). AKI risk factors were assessed using multivariate logistic regression analysis.AKI occurred in 72 (18.9%) patients and was associated with higher mortality than non-AKI patients (26% vs 4%, P < .001). Multivariate logistic regression analysis identified bowel injury, cumulative fluid balance >2.5 L for 24 hours, lactate levels, and vasopressor use (adjusted odds ratio: 2.953, 2.058, 1.170, and 2.910; 95% confidence interval: 1.410–6.181, 1.017–4.164, 1.019–1.343, and 1.414–5.987; P = .004, .045, .026, and .004, respectively) as independent risk factors for AKI.AKI in patients admitted to the ICU with torso injury had a substantial mortality. Recognizing risk factors at an early stage could aid risk stratification and provision of optimal ICU care.

P12: PREDICTORS OF CONVERSION FROM MINIMALLY INVASIVE TO OPEN ADRENALECTOMY: A SYSTEMATIC REVIEW &amp; META-ANALYSIS OF OBSERVATIONAL STUDIES

Abstract Introduction Minimally invasive adrenalectomy has become the standard of care internationally in benign adrenal disease. Intra-operative conversion to open surgery is associated with significantly increased morbidity and prolonged hospital stay. The aim of this systematic review is to identify risk factors associated with intra-operative conversion of minimally invasive adrenalectomy. Method This systematic review was conducted according to MOOSE guidelines. PubMed, EMBASE and Cochrane library were systematically searched for observational studies evaluating risk factors for intra-operative conversion of minimally invasive adrenalectomy to open surgery. Specific risk factors of interest included patient demographics, patient co-morbidities, tumour characteristics and histology. Result Eight studies met the inclusion criteria for analysis with a total of 2939 patients. 6.02% (n=177) required intra-operative conversion. 67.5% (n=1983) underwent laparoscopic transperitoneal adrenalectomy. There were no significant associations between any patient demographics or co-morbidities and intra-operative conversion. Tumour characteristics such as right sided tumours (pooled odds ratio (OR), 1.51; 95% Confidence Interval (CI), 0.98-2.32; p=0.06) and increasing tumour size (OR, 2.29; 95% CI, 1.4-3.74; p=0.001) were shown to be significantly associated with an increased risk of conversion. Pheochromocytoma (OR, 2.21; 95% CI, 1.89-2.58; p&amp;lt;0.0001) and malignancy (OR, 5.38; 95% CI, 2.1-13.81; p=0.005) were also significant predictors of intra-operative conversion. Conclusion Minimally invasive adrenalectomy has significantly reduced post-operative morbidity in patients requiring adrenal surgery but the need for intra-operative conversion remains significant. Identifying patients at increased risk of conversion pre-operatively may assist intra-operative decision making and contribute to improved patient outcomes. Take-home message Minimally invasive adrenalectomy carries a significant risk of conversion. Recognising patients with known risk factors for conversion aids risk stratification and may contribute to better outcomes.

Role of Circulating Tumor DNA in Hematological Malignancy.

Simple SummaryIn recent years, next-generation sequencing has become a major tool in the management of cancer, advancing the diagnosis and treatment of hematological malignancies. However, the gold standard for cancer diagnosis and monitoring still involves invasive and painful procedures, such as tissue and bone marrow biopsies. These procedures involve physical risks, and a single biopsy cannot account for the spatial heterogeneity of tumors. The validity of circulating tumor DNA-mediated liquid biopsies has been receiving increasing attention. This review provides a brief overview of research on liquid biopsy in hematological malignancies, with special emphasis on circulating tumor DNA technologies, which may, in the near future, guide real-world decision making by hematologists.With the recent advances in noninvasive approaches for cancer diagnosis and surveillance, the term “liquid biopsy” has become more familiar to clinicians, including hematologists. Liquid biopsy provides a variety of clinically useful genetic data. In this era of personalized medicine, genetic information is critical to early diagnosis, aiding risk stratification, directing therapeutic options, and monitoring disease relapse. The validity of circulating tumor DNA (ctDNA)-mediated liquid biopsies has received increasing attention. This review summarizes the current knowledge of liquid biopsy ctDNA in hematological malignancies, focusing on the feasibility, limitations, and key areas of clinical application. We also highlight recent advances in the minimal residual disease monitoring of leukemia using ctDNA. This article will be useful to those involved in the clinical practice of hematopoietic oncology.

84 COVID-19 and Associations with Frailty and Multimorbidity: A Prospective Analysis of UK Biobank Participants

IntroductionFrailty and multimorbidity have been suggested as risk factors for severe COVID-19 disease. We therefore investigated whether frailty and multimorbidity were associated with risk of hospitalisation with COVID-19 in the UK Biobank. Method 502,640 participants aged 40–69 years at baseline (54–79 years at COVID-19 testing) were recruited across UK 2006–10. A modified assessment of frailty using Fried’s classification was generated from baseline data. COVID-19 test results (England) were available 16/03/2020–01/06/2020, mostly taken in hospital settings. Logistic regression was used to discern associations between frailty, multimorbidity and COVID-19 diagnoses, adjusting for sex, age, BMI, ethnicity, education, smoking and number of comorbidity groupings, comparing COVID-19 positive, COVID-19 negative and non-tested groups.Results4,510 participants were tested for COVID-19 (positive = 1,326, negative = 3,184). 497,996 participants were not tested. Compared to the non-tested group, after adjustment, COVID-19 positive participants were more likely to be frail (OR = 1.4 [95%CI = 1.1, 1.8]), report slow walking speed (OR = 1.3 [1.1, 1.6]), report two or more falls in the past year (OR = 1.3 [1.0, 1.5]) and be multimorbid (≥4 comorbidity groupings vs 0–1: OR = 1.9 [1.5, 2.3]). However, similar strength of associations were apparent when comparing COVID-19 negative and non-tested groups. Furthermore, frailty and multimorbidity were not associated with COVID-19 diagnoses, when comparing COVID-19 positive and COVID-19 negative participants.ConclusionsFrailty and multimorbidity do not appear to aid risk stratification, in terms of a positive versus negative results of COVID-19 testing. Investigation of the prognostic value of these markers for adverse clinical sequelae following COVID-19 disease is urgently needed.

Respiratory dyssynchrony is a predictor of prognosis in patients with hypertrophic non-obstructive cardiomyopathy

BackgroundRespiratory dyssynchrony (RD) is a phenomenon that may be reflected by reduced breathing efficiency (CO2 output relative to minute ventilation, V̇E/V̇CO2 slope) or by Exercise oscillatory ventilation (EOV). Low breathing efficiency and EOV indicate a worse prognosis in chronic heart failure patients with reduced ejection fraction (HFrEF). However, only little is known about their role in other forms of structural myocardial diseases. In this study, we assessed the prognostic impact of RD in hypertrophic non-obstructive cardiomyopathy (HNCM) as a subgroup of patients with heart failure and preserved ejection fraction (HFpEF). Methods and resultsWe selected n = 132 HNCM patients (pts) who underwent cardiopulmonary exercise testing (CPET) during baseline assessment. The average follow-up was 4.3 ± 3.6 years. The primary endpoint was a composite of death, heart transplantation (HTX), and implantation of a ventricular assist device (VAD).Respiratory dyssynchrony, as measured by EOV, was recorded in 18 pts. (14%), and as measured by a V̇E/V̇CO2 relationship of higher than 34 in 34 pts. (26%).In total, 22 (16.7%) pts. met the endpoint. Multivariate COX regression Analysis were made for EOV, V̇E/V̇CO2 and the combination of EOV andV̇E/V̇CO2. All parameters correlated significantly with the endpoint: EOV (hazard ratio [HR]: 3.7; p = 0.006), V̇E/V̇CO2 > 34 (HR: 5.6; p = 0.001) and EOV andV̇E/V̇CO2: (HR: 6.1; p ≤ 0.001). ConclusionThis is the first study to demonstrate the prognostic impact of RD on pts. with HNCM, and to investigate EOV as a novel factor to aid risk stratification in HNCM.

Socioeconomic and Clinical Predictors of Mortality in Patients with Acute Dyspnea.

BackgroundFactors predicting long-term prognosis in patients with acute dyspnea may guide both acute management and follow-up. The aim of this study was to identify socioeconomic and clinical risk factors for all-cause mortality among acute dyspnea patients admitted to an Emergency Department.MethodsWe included 798 patients with acute dyspnea admitted to the ED of Skåne University Hospital, Malmö, Sweden from 2013 to 2016. Exposures were living in the immigrant-dense urban part of Malmö (IDUD), country of birth, annual income, comorbidities, smoking habits, medical triage priority and severity of dyspnea. Mean follow-up time was 2.2 years. Exposures were related to risk of all-cause mortality using Cox proportional hazard model.ResultsDuring follow-up 40% died. In models adjusted for age and gender, low annual income, previous or ongoing smoking, certain comorbidities, high medical triage priority and severe dyspnea were all significantly associated with increased mortality. After adjusting for age, gender and all significant exposures, the lowest quintile of income, ongoing or previous smoking, history of serious infection, anemia, hip fracture, high medical triage priority and severe dyspnea significantly and independently predicted mortality. In contrast, neither country of birth nor living in IDUD predicted a mortality risk.ConclusionApart from several clinical risk factors, low annual income predicts two-year mortality risk in patients with acute dyspnea. This is not the case for country of birth and living in IDUD. Our results underline the wide range of mortality risk factors in acute dyspnea patients. Knowledge of patients’ annual income as well as certain clinical features may aid risk stratification and determining the need of follow-up both in hospital and after discharge from an ED.

Burkitt Lymphoma International Prognostic Index.

Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches. We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019. In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively. The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.

Current clinical and research fluid biomarkers to aid risk stratification of pancreatic cystic lesions.

Pancreatic cystic lesions (PCL) are composed of a heterogeneous group of entities that are increasingly diagnosed, generally as incidental findings in asymptomatic patients. In conjunction with this growing incidence, the potential for malignant transformation of mucin-producing cysts makes PCL a challenging clinical conundrum for the clinician, patient, and healthcare system. Cyst characterization based on morphology is often difficult and inaccurate. Therefore, several intracystic fluid biomarkers have been evaluated as ancillary testing to enhance the difficult balance between sparing a patient from an unnecessary high-risk pancreatic surgery and missing the opportunity to prevent or diagnose pancreatic adenocarcinoma at an early disease stage. There are two questions that are key to guide the care of patients with PCL: 1) is it a non-mucinous cyst that does not require any follow-up? and 2) if mucinous, does the cyst harbor advanced neoplasia (high-grade dysplasia or invasive carcinoma) that requires surgical resection, or is it a low-risk lesion that will benefit from a surveillance program? The purpose of this review is to give a general and practical overview of the different cyst fluid biomarkers that have been studied to address these specific questions, from classic biochemical markers such as carcinoembryonic antigen to novel genetic and epigenetic markers such as microRNA or intracystic bacterial DNA.

Retrospective validation study of miniPIERS prediction model in Zanzibar.

ObjectiveTo perform a retrospective external validation of miniPIERS in Zanzibar's referral hospital.MethodsFrom February to December 2017, data were collected retrospectively on all cases of hypertensive disorders of pregnancy (HDP) admitted to Mnazi Mmoja Hospital, Zanzibar, Tanzania. The primary outcome was the predictive performance of miniPIERS by examining measures of discrimination, calibration, and stratification accuracy. The secondary outcome was the applicability of miniPIERS within the referral hospital setting.ResultsDuring this period, 2218 of 13 395 (21%) patients were identified with HDP, of whom 594 met the inclusion criteria. Sixty per cent of patients with adverse outcomes were excluded because they had experienced one of the adverse outcomes before admission. The discriminative ability of miniPIERS was inaccurate. It was not likely to aid risk stratification because of low sensitivity and low positive predictive value. The model showed fair discrimination in HDP before 34 weeks of gestation (area under the receiver operating characteristics curve 0.72, 95% confidence interval 0.63–0.82).ConclusionsThe benefit of miniPIERS appeared to be limited, although clinical conditions make any validation challenging. Its application for risk stratification in preterm pregnancies should be further investigated.

COVID-19 and associations with frailty and multimorbidity: a prospective analysis of UK Biobank participants

Frailty and multimorbidity, which are more prevalent in older people, have been suggested as risk factors for severe COVID-19 disease. We investigated whether frailty and multimorbidity were associated with risk of hospitalisation with COVID-19 in the UK Biobank. 502,640 participants aged 40-69 years at baseline (54-79 years at COVID-19 testing) were recruited across UK 2006-10. A modified assessment of frailty using Fried’s classification was generated from baseline data. COVID-19 test results (England) were available 16/03/2020-01/06/2020, mostly taken in hospital settings. Logistic regression was used to discern associations between frailty, multimorbidity and COVID-19 diagnoses, adjusting for sex, age, BMI, ethnicity, education, smoking and number of comorbidity groupings, comparing COVID-19 positive, COVID-19 negative and non-tested groups. 4,510 participants were tested for COVID-19 (positive=1,326, negative=3,184). 497,996 participants were not tested. Compared to the non-tested group, after adjustment, COVID-19 positive participants were more likely to be frail (OR=1.4 [95%CI=1.1, 1.8]), report slow walking speed (OR=1.3 [1.1, 1.6]), report two or more falls in the past year (OR=1.3 [1.0, 1.5]) and be multimorbid (≥4 comorbidity groupings vs 0-1: OR=1.9 [1.5, 2.3]). However, similar strength of associations were apparent when comparing COVID-19 negative and non-tested groups. Furthermore, frailty and multimorbidity were not associated with COVID-19 diagnoses, when comparing COVID-19 positive and COVID-19 negative participants. In conclusion, frailty and multimorbidity do not appear to aid risk stratification, in terms of a positive versus negative results of COVID-19 testing. Investigation of the prognostic value of these markers for adverse clinical sequelae following COVID-19 disease is urgently needed.

Identification of a methylation panel aid in risk stratification in node-positive penile squamous cell carcinoma.

Molecular prognostic factors for individualized treatment of squamous cell carcinoma (SCC) are poorly defined. Our study developed and validated a novel molecular tools aid in preinguinal and postinguinal lymphadenectomy risk stratification in node-positive penile SCC. Patients with node-positive penile SCC who underwent inguinal or ilioinguinal lymphadenectomy were divided into three cohorts: a discovery set, a development set and a validation set. The local ethics committee approved the study. The primary endpoint was cancer-specific survival (CSS). At the discovery stage, 17 CpG sites were significantly associated with CSS. In the development set, we constructed a 3-CpG-based prognostic score for survival prediction. The hazard ratio (HR) of the panel (dichotomized using the optimal cutoff) was 5.8 in the multivariate analyses (P < .001). The addition of the methylation score significantly improved the pN-stage C-index from 0.70 to 0.79 (incremental C = 0.09, P < .001). In the validation set, the methylation panel showed a HR of 9.9 in the multivariate analyses. The addition of the molecular marker improved the pN-stage C-index from 0.69 to 0.78 (incremental C = 0.09, P < .001). The methylation score remarkably separated survival curves in different pN stages, which indicate that the tool can be applied to tailor the treatment in both preinguinal and postinguinal lymphadenectomy settings. We developed and validated a prognostic methylation panel for node-positive penile SCC. The tool may aid in the risk stratification of the population with heterogeneous outcomes and needs prospective validation. Patients in high-risk group may benefit from more aggressive therapy or clinical trials.

A comparative study on the clinical features of COVID‐19 with non‐SARS‐CoV‐2 respiratory viral infections

During this coronavirus disease 2019 (COVID-19) pandemic, physicians have the important task of risk stratifying patients who present with acute respiratory illnesses. Clinical presentation of COVID-19, however, can be difficult to distinguish from other respiratory viral infections. Thus, identifying clinical features that are strongly associated with COVID-19 in comparison to other respiratory viruses can aid risk stratification and testing prioritization especially in situations where resources for virological testing and resources for isolation facilities are limited. In our retrospective cohort study comparing the clinical presentation of COVID-19 and other respiratory viral infections, we found that anosmia and dysgeusia were symptoms independently associated with COVID-19 and can be important differentiating symptoms in patients presenting with acute respiratory illness. On the other hand, laboratory abnormalities and radiological findings were not statistically different between the two groups. In comparing outcomes, patients with COVID-19 were more likely to need high dependency or intensive care unit care and had a longer median length of stay. With our findings, we emphasize that epidemiological risk factors and clinical symptoms are more useful than laboratory and radiological abnormalities in differentiating COVID-19 from other respiratory viral infections.