Carbon Monoxide Diffusion Capacity as a Severity Marker in Pulmonary Hypertension

Carbon monoxide diffusion capacity (DLCO) is negatively associated with patient survival in idiopathic pulmonary hypertension (PH), but is not included in the risk stratification score proposed by the 2015 European guidelines. Since 2015, several new stratification scores based on a 3- or 4-severity scale have been explored. This retrospective cohort single-center study sought to investigate the association between DLCO and PH severity and survival. We included 85 treatment-naive patients with precapillary PH and DLCO measurement at diagnosis. DLCO status, based on lower and upper quartiles ranges, was added to a 3- and a 4-strata modified-risk assessment. DLCO was strongly associated with transplant-free survival (HR 0.939, 95% CI: 0.908–0.971, p < 0.001). In the intermediate and high-risk categories, DLCO was associated with transplant-free survival, irrespective of the risk category (HR 0.934, 95% CI: 0.880–0.980, p = 0.005). The correlation between modified-risk category and transplant-free survival was significant (HR 4.60, 95% CI: 1.294–16.352, p = 0.018). Based on the Akaike information criterion (AIC) levels, the 3- and 4-strata modified-risk stratification fits our results better than the conventional stratification. Low DLCO is associated with patient transplant-free survival, independently of the risk category. Inclusion of DLCO into a PH risk stratification score seems promising and needs further investigation.

Validation of the risk stratification score in idiopathic pulmonary fibrosis: study protocol of a prospective, multi-centre, observational, 3-year clinical trial

Background Idiopathic pulmonary fibrosis (IPF) is characterized by a poor prognosis, with a progressive decline in lung function and considerable variability in the disease’s natural history. Besides lung transplantation (LTx), the only available treatments are anti-fibrosing drugs, which have shown to slow down the disease course. Therefore, predicting the prognosis is of pivotal importance to avoid treatment delays, which may be fatal for patients with a high risk of progression. Previous studies showed that a multi-dimensional approach is practical and effective in the development of a reliable prognostic score for IPF. In the RIsk Stratification scorE (RISE), physiological parameters, an objective measure of patient-reported dyspnea and exercise capacity are combined to capture different domains of the complex pathophysiology of IPF. Methods This is an observational, multi-centre, prospective cohort study, designed to reflect common clinical practice in IPF. A development cohort and a validation cohort will be included. Patients newly diagnosed with IPF based on the ATS/ERS criteria and multi-disciplinary discussion will be included in the study. A panel of chest radiologists and lung pathologists will further assess eligibility. At the first visit (time of diagnosis), and every 4-months, MRC dyspnea score, pulmonary function tests (FEV1, FVC and DLCO), and 6-min walking distance will be recorded. Patients will be prospectively followed for 3 years. Comorbidities will be considered. The radiographic extent of fibrosis on HRCT will be recalculated at a 2-year interval. RISE, Gender-Age-Physiology, CPI and Mortality Risk Scoring System will be calculated at 4-month intervals. Longitudinal changes of each variable considered will be assessed. The primary endpoint is 3-year LTx-free survival from the time of diagnosis. Secondary endpoints include several, clinically-relevant information to ensure reproducibility of results across a wide range of disease severity and in concomitance of associated pulmonary hypertension or emphysema. Discussion The objective of this study is to validate RISE as a simple, straightforward, inexpensive and reproducible tool to guide clinical decision making in IPF, and potentially as an endpoint for future clinical trials. Trial registration: U.S National Library of Medicine Clinicaltrials.gov, trial n. NCT02632123 “Validation of the risk stratification score in idiopathic pulmonary fibrosis”. Date of registration: December 16th, 2015.

SP4.2.7 Outcomes following reorganisation of colorectal cancer pathway using FIT testing and a locally developed risk stratification score in a busy District General Hospital in United Kingdom during the COVID-19 pandemic

Aims/Introduction Limited availability of endoscopy and CT colonography led to significant pressures on the colorectal cancer pathway during the COVID-19 pandemic. Risk stratification was necessary to determine the order in which patients on the tracking list could access diagnostics. Based on national guidance, patient symptoms and FIT test results, we used a locally developed risk stratification score (RSS). The aim of this study was to evaluate the impact the RSS had on patient diagnoses over a period of 8 months Methodology A prospectively maintained database was used to assess the outcomes. Based on their symptoms, patients on the colorectal 2ww pathway were invited to provide FIT samples if eligible. Diagnostics were prioritised using RSS. Results were analysed to assess how the cancer diagnostic yield during the pandemic compared to a similar period the year before. Results There were 1133 patients referred on the colorectal 2ww pathway between May - December 2020. 884 of these patients had FIT testing and 249 were not eligible. Of the 69 colorectal cancers diagnosed, 25 were in the FIT group and 44 in those not eligible. The RSS stratified to high or indeterminate risk in the non-FIT group was 31 and 23 in the FIT group. Compared to the previous year’s number of 59 patients diagnosed between May - December 2019, no statistical difference was found. Conclusion Our study shows that FIT testing and RSS led to an equivalent pick up rate of colorectal cancer and can be utilised in clinical settings with limited resources.

Cardiac Toxicity after Matched Allogeneic Hematopoietic Cell Transplantation in the Post-Transplant Cyclophosphamide Era

Graft-versus-host-disease (GVHD) is one of the leading causes of non-relapse mortality (NRM) following allogeneic hematopoietic cell transplantation (alloHCT). Post-transplant cyclophosphamide (PTCy) has shown promise in managing GVHD. However, cyclophosphamide has known cardiac toxicities and few studies have evaluated the cardiac toxicities that arise following PTCy. Here, we completed a retrospective analysis of matched alloHCT patients at our institution who received PTCy or non-PTCy-based GVHD prophylaxis, with the goal of determining the incidence of cardiac toxicities up to 100 days after alloHCT. We included 585 patients in our analysis and found that 38 patients (6.5%) experienced cardiac toxicities after alloHCT. The toxicities observed included arrhythmias (n=21), heart failure (n=14), pericardial effusions (n=10), and myocardial infarction or ischemia (n=7). Patients who received PTCy had a 7.4% incidence of cardiac toxicities, while non-PTCy patients had an incidence of 5.8% (p=0.4). We found that age &gt; 55 years (p=0.02), history of hypertension (p=0.01), arrhythmia (p=0.003), diabetes (p=0.04), and cardiac comorbidities (p&lt;0.001) were significant predictors of cardiac toxicity, while none of the preparative and GVHD prophylaxis regimens used were predictive of cardiac toxicity. From these findings, we proposed the use of a Cardiac Risk Stratification Score to quantify the risk of cardiac toxicity following alloHCT and found that a higher score correlated with cardiac toxicity incidence. Furthermore, the development of cardiac toxicity was associated with worse 1-yr overall survival (OS) and NRM while the use of PTCy was associated with improvements in 1-year OS and NRM rates.

The New Era of TIRADSs to Stratify the Risk of Malignancy of Thyroid Nodules: Strengths, Weaknesses and Pitfalls

Since 2009, thyroid imaging reporting and data systems (TI-RADS) have been playing an increasing role in the field of thyroid nodules (TN) imaging. Their common aims are to provide sonologists of varied medical specialties and clinicians with an ultrasound (US) based malignancy risk stratification score and to guide decision making of fine-needle aspiration (FNA). Schematically, all TI-RADSs scores can be classified as either pattern-based or point-based approaches. The main strengths of these systems are their ability (i) to homogenize US TN descriptions among operators, (ii) to facilitate and shorten communication on the malignancy risk of TN between sonologists and clinicians, (iii) to provide quantitative ranges of malignancy risk assessment with high sensitivity and negative predictive values, and (iv) to reduce the number of unnecessary FNAs. Their weaknesses are (i) the remaining inter-observer discrepancies and (ii) their insufficient sensitivity for the diagnosis of follicular cancers and follicular variant of papillary cancers. Most common pitfalls are degenerating shrinking nodules and confusion between individual and coalescent nodules. The benefits of all TI-RADSs far outweigh their shortcomings, explaining their rising use, but the necessity to improve and merge the different existing systems remains.

Utilization of Lrinec Score for Early Diagnosis of a Necrotizing Soft Tissue Infection by Serratia Marcesens Complicated with Deep Vein Thrombosis

Necrotizing fasciitis (NF) has a rapid clinical course and is associated with high mortality. Moreover, it involves a high index of suspicion and early aggressive intervention to reduce the risk of mortality. The overlap in clinical presentation in similar pathologies like abscesses, cellulitis, and deep vein thrombosis, can mask underlying NF, making the diagnosis even more challenging. This case presents multiple comorbidities that expedited the development of NF, while demonstrating a pragmatic approach to treating NF while balancing anticoagulation and emergent surgical intervention. The utilization of clinical judgement and a risk stratification score can help identify early cases of NF allowing for aggressive intervention.