BurkDiff: A Real-Time PCR Allelic Discrimination Assay for Burkholderia Pseudomallei and B. mallei

A real-time PCR assay, BurkDiff, was designed to target a unique conserved region in the B. pseudomallei and B. mallei genomes containing a SNP that differentiates the two species. Sensitivity and specificity were assessed by screening BurkDiff across 469 isolates of B. pseudomallei, 49 isolates of B. mallei, and 390 isolates of clinically relevant non-target species. Concordance of results with traditional speciation methods and no cross-reactivity to non-target species show BurkDiff is a robust, highly validated assay for the detection and differentiation of B. pseudomallei and B. mallei

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

A Phase III Randomized Trial of Gemcitabine–Oxaliplatin versus Carboplatin–Paclitaxel as First-Line Therapy in Patients with Advanced Non-small Cell Lung Cancer

Purpose:This phase III study compared the efficacy and tolerability of gemcitabine and oxaliplatin (GEMOX) with paclitaxel and carboplatin (PCb) in chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer.Patients and Methods:Patients aged 18 years or older were randomized to PCb (paclitaxel 225 mg/m2 followed by carboplatin area under the curve = 6 on day 1 every 3 weeks) or GEMOX (gemcitabine 1,000 mg/m2 on days 1 and 8 followed by oxaliplatin 130 mg/m2 on day 1 every 3 weeks) for up to six cycles. The primary end point was progression-free survival (PFS), with tumor response rate, overall survival (OS), and quality of life as secondary end points.Results:The study was terminated after 383 patients had been randomized (371 received treatment) as the incidence of adverse events had exceeded the protocol-specified safety threshold (≥20% in either arm). No formal statistical comparisons were conducted. Median PFS was 4.44 months and 4.67 months in the GEMOX and PCb groups, respectively. Objective response rates (complete or partial) were 15.2% and 22.4% in the GEMOX and PCb arms, respectively. Median OS was 9.90 months (GEMOX) and 9.24 months (PCb); post hoc analyses showed median OS in patients aged 70 years or older to be similar to those younger than 70 years. PFS was similar in both groups of patients with adenocarcinoma histology, although OS favored the GEMOX group. Quality of life was improved from baseline in both groups. Toxicity profiles were comparable between the groups.Conclusion:PFS, OS, and objective response rates with GEMOX were similar to PCb. Nevertheless, toxicities limit the adoption of this regimen for routine use in advanced non-small cell lung cancer

901-33 Should Age be a Consideration in Mode Selection in Permanent Pacing? A Survival Analysis

Although it has been suggested that functional benefits from dual-chamber pacing may be greater in the elderly than in the younger patient population partially due to age-related decrease in cardiac compliance, the relative impact on long-term survival with respect to mode of pacing and age has not been established. To assess interactions between age and pacing mode, we analyzed survival outcome of 631 patients ≥70 yrs of age paced between 1980 to 1985. There were 260 women and 371 men. Mean age was 78±6 yrs (range 70 to 98 yrs), and mean follow-up was 5.2±3.2 yrs. Forward step-wise Cox regression analysis identified several independent risk factors for increased mortality, including: age, CHF, Ml, diabetes, renal failure, and cancer. Dual-chamber pacing was also an independent predictor for improved survival (X2=11.4, p≤0.0001). Survival was further analyzed, stratified by both age and pacing mode as shown below:AgePacing mode (n)Probability of Survival 1%)Log Rank p1yr3yr5yr≥80Dual (51)9682640.0014Single (166)816144<80Dual (155)8878670.3556Single (259)907759When the interaction between pacing mode and age was included in the multivariate proportional hazard model, there was a clear trend of interaction (X2=3,46, p=0.06). These findings suggest that beneficial effects of dual chamber pacing on long-term survival may be greater in older patients. Selection of dual chamber pacing should be considered in the elderly

740-3 Differential Impact of Pacing Mode on Long-term Survival In Patients with Conduction System Disease

Advantages of dual chamber (DC) pacing compared to single chamber (SC) pacing have been recognized. However, the differential impact of pacing mode on long-term survival with respect to conduction abnormalities is not well established. We analyzed survival outcome in 631 pts who received permanent pacemaker for conduction system disease from 1980 to 1985. There were 245 pts (39%) with sick sinus syndrome (SSS), 386 pts (61%) with atrial ventricular block IAVB). Mean age was 78±6 years; mean follow up was 5.2±3.2 years. Observed survivals according to pacing mode and types of conduction system disease are summarized below (Kaplan-Meier method).Conduction system diseasePacing Mode (n)Probability of Survival (%)Log rank P1 yr3 yr5 yrSSSDual (83)8973590.6458Single (162)897360AVBDual (123)9083720.0005Single (263)856953Cox multivariate analysis identified several independent risk factors for increased mortality including age, CHF, MI, diabetes mellitus, renal failure, and cancer.Conclusions1. Based on mode of pacing, long-term survivals were not significantly different between DC and SC pacing in pts with SSS. 2. In pts with AVB, DC pacing is associated with improved survival. 3. These observations do not support the notion that SC pacing increases mortality in pts with SSS