Oakwood Hospital

BackgroundEuropean guidelines advise that patients suffering ST-segment elevation myocardial infarction (STEMI) should be revascularized within 120 minutes of diagnosis. The preferred method of revascularization is primary percutaneous coronary intervention (pPCI). We analysed the Northern Irish STEMI database to establish the proportion of pPCI delivered within the recommended treatment window, and determined whether there was any difference in long-term survival for patients treated beyond the recommended time window.MethodsData were collected on all STEMIs from the 2 pPCI centres in Northern Ireland from January 2013 – March 2018. Patients were grouped based on time from ECG to revascularization – those <120 mins: Timely group; those ≥ 120 mins: Delayed group. All-cause mortality was determined form a national health record. Statistical analyses were performed using Stata.Results3,250 patients were included in the analysis, 2,590 timely and 660 delayed. All patients received pPCI. Patients in the delayed group were older, more likely to be female and/or diabetic, and lived further away from the pPCI centre. A summary of baseline characteristics is reported below in Table 1. Delayed pPCI was associated with a significantly increased mortality: unadjusted HR 1.58 (95%CI 1.32-1.90, p<0.000). Unadjusted survival curves are displayed below in Figure 1. Unadjusted Log-Rank p<0.000. Following Cox multivariate regression, adjusted HR for mortality was 1.38 (95%CI 1.09-1.73, p=0.006) for delayed pPCI.ConclusionSystem delay resulting in primary PCI beyond 120 minutes from diagnostic ECG is associated with a significantly increased risk of mortality following STEMI in Northern Ireland. 45 Table 1Baseline characteristicsTimelyDelayedp valueAge (mean)62.8yrs65.0yrs<0.00Female24.9%30.2%<0.00Smoker43.6%38.7%0.054Diabetes13.9%19.0%0.002Age ≥ 7519.3%26.1%<0.00BMI (mean)27.727.70.94Proximity to pPCI centre28.6km39.9km<0.00 45 Figure 1Crude all-cause mortality following STEMI , timely vs delayed pPCIConflict of InterestNone

Positive margins following breast-conserving surgery (BCS) are often identified on standard pathology evaluation. Intraoperative assessment of the lumpectomy cavity has the potential to reduce residual disease or reexcision rate following standard of care BCS in real time. To collect safety and initial efficacy data on the novel pegulicianine fluorescence-guided system (pFGS) when used to identify residual cancer in the tumor bed of female patients undergoing BCS. This prospective single-arm open-label study was conducted as a nonrandomized multicenter controlled trial at 16 academic or community breast centers across the US. Female patients 18 years and older with newly diagnosed primary invasive breast cancer or ductal carcinoma in situ DCIS undergoing BCS were included, excluding those with previous breast cancer surgery and a history of dye allergies. Of 283 consecutive eligible patients recruited, 234 received a pegulicianine injection and were included in the safety analysis; of these, 230 were included in the efficacy analysis. Patients were enrolled between February 6, 2018, and April 10, 2020, and monitored for a 30-day follow-up period. Data were analyzed from April 10, 2020, to August 5, 2021. Participants received an injection of a novel imaging agent (pegulicianine) a mean (SD) of 3.2 (0.9) hours prior to surgery at a dose of 1 mg/kg. After completing standard of care (SOC) excision, pFGS was used to scan the lumpectomy cavity to guide the removal of additional shave margins. Adverse events and sensitivity, specificity, and reexcision rate. Of 234 female patients enrolled (median [IQR] age, 62.0 [55.0-69.0] years), 230 completed the trial and 1 patient with a history of allergy to contrast agents had an anaphylactic reaction and recovered without sequelae. Correlation of pFGS with final margin status on a per-margin analysis showed a marked improvement in sensitivity over standard pathology assessment of the main lumpectomy specimen (69.4% vs 38.2%, respectively). On a per-patient level, the false-negative rate of pFGS was 23.7% (9 of 38), and sensitivity was 76.3% (29 of 38). Among 32 patients who underwent excision of pFGS-guided shaves, pFGS averted the need for reexcision in 6 (19%). In this pilot feasibility study, the safety profile of pegulicianine was consistent with other imaging agents used in BCS, and was associated with a reduced need for second surgery in patients who underwent intraoperative additional excision of pFGS-guided shaves. These findings support further development and clinical performance assessment of pFGS in a prospective randomized trial. ClinicalTrials.gov Identifier: NCT03321929.

INTRODUCTION: Increased body mass index (BMI) is a recognized risk factor for the development of colo-rectal cancer (CRC). Although the incidence of adenoma clearly correlates with risk of CRC, the relationship between the presence of adenomas and BMI has not been consistently demonstrated among all populations especially African Americans (AA). The objective of this study was to evaluate the correlation between adenomas and BMI in AA as compared to Non-AA. METHODS: From a database of 1010 patients undergoing screening or surveillance colonoscopy in the last 6 months of 2017, we identified 729 patients whose colonoscopy was performed only by academic gastroenterologists (GI). There were 648 AA (89%) and 81 non-AA in the study with an average age of 58 and similar gender (54% female). The BMI (kg/m2) was slightly higher in females as compared to males (31.7 ± 0.3 vs 28.9 ± 0.38 P < 0.001) but was not different by race (30.5 vs 29.6). BMI was evaluated both as a continuous variable and categorical using the standard definitions (normal <25, overweight (25–30) and obese (<30)). RESULTS: There were 244 individuals with adenomas in the 574 screening colonoscopies (43%) and 79 in the 135 surveillance colonoscopies (59%) (P < 0.001). When comparing Non-AA patients to AA patients using Logistic Fit models, Non-AA patients had an increase in adenomas detected with the increase in BMI (P < 0.016). In contrast, AA had a decrease in individuals found to have adenomas with the increase in BMI (P = 0.22 Probability > ChiSq) (Figure 1). The increase in individuals with adenomas was more likely to be in the male AA as compared to the females. In non-AA patients, both males and females were more likely to have an adenoma with the increase in BMI. Similar observations were made for both surveillance and screening colonoscopies. When patient BMI was categorized as normal, overweight, or obese, the relationship was similar (Figure 2).Figure 1.: Correlation between BMI and Presence of Adenoma by Race. Non-AA had an increase in Adenomas with increase in BMI whereas AA individuals had a decline.CONCLUSION: Unlike in non-AA individuals, an increase in BMI in AA individuals does not correlate with the detection of adenoma’s on colonoscopy. In contrast to most of the literature, this study reduces the role of variation in endoscopists by using the high adenoma detection rate academic GI physicians and a homogeneous population with respect to gender and age. The reason that BMI does not correlate with the detection of adenomas in AA patients is not known.Figure 2.: Correlation between BMI category (normal, overweight or obese) and the Presence of Adenoma by Race. In contrast to Non-AA individuals, AA did not have an increase in Adenomas Detection Rate with increasing BMI.

An informed consent conversation examining relevant research and discussing the potential benefits and harms of thrombolytic therapy in acute stroke.

Objective adherence to inhaled therapy by patients with chronic obstructive pulmonary disease (COPD) has not been reported. To objectively quantify adherence to preventer Diskus inhaler therapy by patients with COPD with an electronic audio recording device (INCA). This was a prospective observational study. On discharge from hospital patients were given a salmeterol/fluticasone inhaler with an INCA device attached. Analysis of this audio quantified the frequency and proficiency of inhaler use. Patients with COPD (n = 244) were recruited. The mean age was 71 years, mean FEV1 was 1.3 L, and 59% had evidence of mild/moderate cognitive impairment. By combining time of use, interval between doses, and critical technique errors, thus incorporating both intentional and unintentional nonadherence, a measure "actual adherence" was calculated. Mean actual adherence was 22.6% of that expected if the doses were taken correctly and on time. Six percent had an actual adherence greater than 80%. Hierarchical clustering found three equally sized well-separated clusters corresponding to distinct patterns. Cluster 1 (34%) had low inhaler use and high error rates. Cluster 2 (25%) had high inhaler use and high error rates. Cluster 3 (36%) had overall good adherence. Poor lung function and comorbidities were predictive of poor technique, whereas age and cognition with poor lung function distinguished those with poor adherence and frequent errors in technique. These data may inform clinicians in understanding why a prescribed inhaler is not effective and to devise strategies to promote adherence in COPD.

A substantial number of patients diagnosed with high-risk prostate cancer are at risk for metastatic progression after primary treatment. Better biomarkers are needed to identify patients at the highest risk to guide therapy intensification. To create a DNA damage and repair (DDR) pathway profiling method for use as a prognostic signature biomarker in high-risk prostate cancer. A cohort of 1090 patients with high-risk prostate cancer who underwent prostatectomy and were treated at 3 different academic institutions were divided into a training cohort (n = 545) and 3 pooled validation cohorts (n = 232, 130, and 183) assembled for case-control or case-cohort studies. Profiling of 9 DDR pathways using 17 gene sets for GSEA (Gene Set Enrichment Analysis) of high-density microarray gene expression data from formalin-fixed paraffin-embedded prostatectomy samples with median 10.3 years follow-up was performed. Prognostic signature development from DDR pathway profiles was studied, and DDR pathway gene mutation in published cohorts was analyzed. Biochemical recurrence-free, metastasis-free, and overall survival. Across the training cohort and pooled validation cohorts, 1090 men were studied; mean (SD) age at diagnosis was 65.3 (6.4) years. We found that there are distinct clusters of DDR pathways within the cohort, and DDR pathway enrichment is only weakly correlated with clinical variables such as age (Spearman ρ [ρ], range, -0.07 to 0.24), Gleason score (ρ, range, 0.03 to 0.20), prostate-specific antigen level (ρ, range, -0.07 to 0.10), while 13 of 17 DDR gene sets are strongly correlated with androgen receptor pathway enrichment (ρ, range, 0.33 to 0.82). In published cohorts, DDR pathway genes are rarely mutated. A DDR pathway profile prognostic signature built in the training cohort was significantly associated with biochemical recurrence-free, metastasis-free, and overall survival in the pooled validation cohorts independent of standard clinicopathological variables. The prognostic performance of the signature for metastasis-free survival appears to be stronger in the younger patients (HR, 1.67; 95% CI, 1.12-2.50) than in the older patients (HR, 0.77; 95% CI, 0.29-2.07) on multivariate Cox analysis. DNA damage and repair pathway profiling revealed patient-level variations and the DDR pathways are rarely affected by mutation. A DDR pathway signature showed strong prognostic performance with the long-term outcomes of metastasis-free and overall survival that may be useful for risk stratification of high-risk prostate cancer patients.