Pooled Analysis Of Individual Patient Data Research Articles

Stenting for symptomatic intracranial arterial stenosis with different qualifying arteries: a preplanned pooled individual patient data analysis

BackgroundThe efficacy of percutaneous transluminal angioplasty and stenting (PTAS) relative to medical management in treating symptomatic intracranial arterial stenosis (ICAS) varies based on the qualifying artery. This study aims to...

Stenting versus medical treatment alone for symptomatic intracranial artery stenosis: a preplanned pooled individual patient data analysis

BackgroundWhether the safety and efficacy of percutaneous transluminal angioplasty and stenting (PTAS) is significantly different from that of medical treatment alone for symptomatic intracranial arterial stenosis (ICAS) is debatable. A...

Association between overweight and obesity with coronary artery bypass graft failure: an individual patient data analysis of clinical trials.

The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated. We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed. Six trials comprising 3928 patients and 12048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97-0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64-0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64-1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45-0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62-1.42)] patients. Findings were similar, but did not reach significance, at the patient level. In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.

Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries

BackgroundWe investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation.MethodsThis is an individual patient...

Intraarrest transport, extracorporeal cardiopulmonary resuscitation, and early invasive management in refractory out-of-hospital cardiac arrest: an individual patient data pooled analysis of two randomised trials.

Refractory out-of-hospital cardiac arrest (OHCA) treated with standard advanced cardiac life support (ACLS) has poor outcomes. Transport to hospital followed by in-hospital extracorporeal cardiopulmonary resuscitation (ECPR) initiation may improve outcomes. We performed a pooled individual patient data analysis of two randomised controlled trials evaluating ECPR based approach in OHCA. The individual patient data from two published randomised controlled trials (RCTs) were pooled: ARREST (enrolled Aug 2019-June 2020; NCT03880565) and PRAGUE-OHCA (enrolled March 1, 2013-Oct 25, 2020; NCT01511666). Both trials enrolled patients with refractory OHCA and compared: intra-arrest transport with in-hospital ECPR initiation (invasive approach) versus continued standard ACLS. The primary outcome was 180-day survival with favourable neurological outcome (defined as Cerebral Performance Category 1-2). Secondary outcomes included: cumulative survival at 180 days, 30-day favourable neurological survival, and 30-day cardiac recovery. Risk of bias in each trial was assessed by two independent reviewers using the Cochrane risk-of-bias tool. Heterogeneity was assessed via Forest plots. The two RCTs included 286 patients. Of those randomised to the invasive (n=147) and standard (n=139) groups, respectively: the median age was 57 (IQR 47-65) and 58 years (IQR 48-66), and the median duration of resuscitation was 58 (IQR 43-69) and 49 (IQR 33-71) minutes (p=0.17). In a modified intention to treat analysis, 45 (32.4%) in the invasive and 29 (19.7%) patients in the standard arm survived to 180 days with a favourable neurological outcome [absolute difference (AD), 95% CI: 12.7%, 2.6-22.7%, p=0.015]. Forty-seven (33.8%) and 33 (22.4%) patients survived to 180 days [HR 0.59 (0.43-0.81); log rank test p=0.0009]. At 30 days, 44 (31.7%) and 24 (16.3%) patients had favourable neurological outcome (AD 15.4%, 5.6-25.1%, p=0.003), 60 (43.2%), and 46 (31.3%) patients had cardiac recovery (AD: 11.9%, 0.7-23%, p=0.05), in the invasive and standard arms, respectively. The effect was larger in patients presenting with shockable rhythms (AD 18.8%, 7.6-29.4; p=0.01; HR 2.26 [1.23-4.15]; p=0.009) and prolonged CPR (>45min; HR 3.99 (1.54-10.35); p=0.005). In patients with refractory OHCA, the invasive approach significantly improved 30- and 180-day neurologically favourable survival. None.

Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a pooled individual patient data analysis

BackgroundProne positioning (PP) reduces mortality of patients with acute respiratory distress syndrome (ARDS). The potential benefit of prone positioning maneuvers during venovenous extracorporeal membrane oxygenation (ECMO) is unknown. The aim of this study was to evaluate the association between the use of prone positioning during extracorporeal support and ICU mortality in a pooled population of patients from previous European cohort studies.MethodsWe performed a pooled individual patient data analysis of European cohort studies which compared patients treated with prone positioning during ECMO (Prone group) to “conventional” ECMO management (Supine group) in patients with severe ARDS.Results889 patients from five studies were included. Unadjusted ICU mortality was 52.8% in the Supine Group and 40.8% in the Prone group. At a Cox multiple regression analysis PP during ECMO was not significantly associated with a reduction of ICU mortality (HR 0.67 95% CI: 0.42–1.06). Propensity score matching identified 227 patients in each group. ICU mortality of the matched samples was 48.0% and 39.6% for patients in the Supine and Prone group, respectively (p = 0.072).ConclusionsIn a large population of ARDS patients receiving venovenous extracorporeal support, the use of prone positioning during ECMO was not significantly associated with reduced ICU mortality. The impact of this procedure will have to be definitively assessed by prospective randomized controlled trials.

Prevalence of nodal involvement in rectal cancer after chemoradiotherapy.

The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data. Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS). Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death. Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.

Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. British Heart Foundation and Stroke Association.

Safety of low-dose oral minoxidil treatment for hair loss. A systematic review and pooled-analysis of individual patient data.

low dose oral minoxidil (OM) is an increasingly used treatment for androgenetic alopecia and other types of hair loss. to analyze available data of patients treated with OM, focusing on safety and adverse effects. a search in PubMed and EMBASE was performed for studies reporting the treatment of alopecia with OM. Individual patient data available for pooled-analysis were sex, dose of OM, presence of hypertrichosis and lower limb edema. 14 studies including 442 patients were analyzed. OM was used at doses between 0.25 and 5 mg, for eight different types of alopecia. Hypertrichosis was observed in 24% of patients. All doses had an increased odds ratio of hypertrichosis, compared to 0.25 to 0.5 mg (P < .001). Pedal edema was observed in 2% and was also associated with higher doses of OM (P = .009). Postural hypotension and heart rate alterations occurred only in 1.1% and 1.3% of the patients, respectively. Efficacy of OM could not be analyzed due to heterogeneous studies. However, four studies using OM for androgenetic alopecia reported a clinical response in 70% to 100% of the patients. Low dose OM is a safe and well-tolerated treatment for hair loss, presenting a lower adverse effect rate than standard doses.

Stenting for symptomatic vertebral artery stenosis: a preplanned pooled individual patient data analysis

Symptomatic vertebral artery stenosis is associated with a high risk of recurrent stroke, with higher risks for intracranial than for extracranial stenosis. Vertebral artery stenosis can be treated with stenting with good technical results, but whether it results in improved clinical outcome is uncertain. We aimed to compare vertebral stenting with medical treatment for symptomatic vertebral stenosis. We did a preplanned pooled individual patient data analysis of three completed randomised controlled trials comparing stenting with medical treatment in patients with symptomatic vertebral stenosis. The primary outcome was any fatal or non-fatal stroke. Analyses were performed for vertebral stenosis at any location and separately for extracranial and intracranial stenoses. Data from the intention-to-treat analysis were used for all studies. We estimated hazard ratios (HRs) with 95% CIs using Cox proportional-hazards regression models stratified by trial. Data were from 354 individuals from three trials, including 179 patients from VIST (148 with extracranial stenosis and 31 with intracranial stenosis), 115 patients from VAST (96 with extracranial stenosis and 19 with intracranial stenosis), and 60 patients with intracranial stenosis from SAMMPRIS (no patients had extracranial stenosis). Across all trials, 168 participants (46 with intracranial stenosis and 122 with extracranial stenosis) were randomly assigned to medical treatment and 186 to stenting (64 with intracranial stenosis and 122 with extracranial stenosis). In the stenting group, the frequency of periprocedural stroke or death was higher for intracranial stenosis than for extracranial stenosis (ten (16%) of 64 patients vs one (1%) of 121 patients; p<0·0001). During 1036 person-years of follow-up, the hazard ratio (HR) for any stroke in the stenting group compared with the medical treatment group was 0·81% CI 0·45-1·44; p=0·47). For extracranial stenosis alone the HR was 0·63 (95% CI 0·27-1·46) and for intracranial stenosis alone it was 1·06 (0·46-2·42; pinteraction=0·395). Stenting for vertebral stenosis has a much higher risk for intracranial, compared with extracranial, stenosis. This pooled analysis did not show evidence of a benefit for stroke prevention for either treatment. There was no evidence of benefit of stenting for intracranial stenosis. Stenting for extracranial stenosis might be beneficial, but further larger trials are required to determine the treatment effect in this subgroup. None.

Abstract WP519: Ischemic Stroke Despite Oral Anticoagulant Therapy in Patients With AF - What is the Risk of Recurrence and How to Prevent Further Events?

Background: It is unknown whether patients with atrial fibrillation (AF) having an ischemic stroke despite preventive oral anticoagulant therapy are at increased risk for further recurrent strokes and how secondary prevention should be managed. Methods: We conducted a pooled individual patient data analysis of 7 prospective cohort studies recruiting patients with AF and an index event (ischemic stroke or TIA). We compared patients taking oral anticoagulants (Vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OAC prior ) with those without prior anticoagulation (OAC naive ). We further compared those who changed the type (i.e. from VKA or DOAC or vice versa) of anticoagulation (OAC changed ) with those who continued the same anticoagulation as secondary prevention (OAC unchanged ). Time-to-endpoint was analysed using multivariate cox proportional hazard regression models with frailty term for study and calculating hazard ratios (HR) with corresponding 95% confidence intervals. Results: We included 5413 patients (median age 78years [IQR 71-84years], 5136 [96.7%] had ischemic stroke as index event, median NIHSS-on-admission 6 [IQR 2-12]). The median CHA 2 DS 2 -Vasc score was 5 (IQR4-6) and not different (p=0.103) between prior OAC (n=1195) and OAC naive (n=4119). During follow-up of 6128 patient years, 289 patients had recurrent ischemic stroke (AIS, 4.7%/year, 95%CI 4.2-5.3%). prior OAC was independently associated with an increased risk of AIS (HR 1.6, 95%CI 1.1-2.1, p=0.006). OAC changed (n=307) was not associated with decreased risk of AIS (HR 1.3, 95%CI 0.8-2.2, p=0.326) compared to OAC unchanged (n=585). Conclusion: Patients with AF who failed oral anticoagulation once are at a higher risk for further ischemic strokes although the CHA 2 DS 2 -Vasc scores did not differ between both groups.

Efficacy of zofenopril in combination with amlodipine in patients with acute myocardial infarction: a pooled individual patient data analysis of four randomized, double-blind, controlled, prospective studies

Objective: In the four SMILE (Survival of Myocardial Infarction Long-Term Evaluation) studies, early administration of zofenopril in acute myocardial infarction (AMI) showed beneficial effects as compared to placebo and other angiotensin converting enzyme inhibitors (ACEIs). This study investigated whether the concomitant administration of the dihydropyridine calcium channel-blocker amlodipine may improve zofenopril efficacy to prevent cardiovascular events in post-AMI patients.Methods: This was a post-hoc analysis of pooled individual patient data from the four large randomized SMILE studies. The primary endpoint was the 1-year combined occurrence of death or hospitalization for cardiovascular causes.Results: In total, 3488 patients were considered, 303 (8.7%) treated with concomitant amlodipine. Baseline systolic blood pressure and prevalence of metabolic syndrome were higher in amlodipine treated patients. The 1-year occurrence of major cardiovascular outcomes was significantly reduced in patients receiving concomitant treatment with amlodipine (hazard ratio, HR = 0.66; and 95% confidence interval, CI = 0.44–0.98; p = .039). After accounting for treatment with amlodipine, the risk of cardiovascular events was significantly reduced with zofenopril compared to placebo (HR = 0.78; 95% CI = 0.63–0.97; p = .026]. Among ACEI-treated patients, the zofenopril plus amlodipine combination reduced the risk of cardiovascular events by 38%, compared to the combination of other ACEIs plus amlodipine [HR = 0.76; 95% CI = 0.61–0.94); p = .013). The prognostic benefit of concomitant treatment with zofenopril plus amlodipine was independent from blood pressure lowering.Conclusions: Zofenopril had a positive impact on prognosis in post-AMI patients, compared to other ACEIs. Concomitant administration of amlodipine may help to reduce the risk of cardiovascular events at 1 year.

Mechanical ventilation during low-flow extracorporeal carbon dioxide removal and outcome in patients with acute respiratory distress syndrome: A pooled individual patient data analysis of 5 studies

Linalool and geraniol are the primary components of rose oil, palmarosa oil, and citronella oil and many other essential oils, and two important compounds used in the flavour and fragrance, cosmetic or pharmaceutical industries. Phase equilibria (LLE, VLE, solubility, etc.) and related thermodynamic properties of a mixture are essential in the processes design and control of mass transfer process. In this work, experimental (liquid + liquid) equilibria data of the systems (water + 1-propanl + linalool) and (water + 1-propanl + geraniol) are presented. The (liquid + liquid) equilibria of both systems were determined with a tie-line method at T = (283.15, 298.15 and 313.15) K under atmospheric pressure. The well-known Hand, Bachman and Othmer–Tobias equations were used to test the reliability of the experimental values. The influence of the temperature on the (liquid + liquid) phase equilibria of the mixtures, the binodal curves and distribution ratios of 1-propanl are shown and discussed. Moreover, the NRTL and UNIQUAC models were applied to fit the data for both ternary systems. The interaction parameters obtained from both models successfully correlated the equilibrium compositions. Furthermore, the ternary systems could be represented using the binary parameters of the thermodynamic model with a function of temperature.

Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies

Identification of patients at highest risk of early stroke after transient ischaemic attack has been improved with imaging based scores. We aimed to compare the validity and prognostic utility of imaging-based stroke risk scores in patients after transient ischaemic attack. We did a pooled analysis of published and unpublished individual-patient data from 16 cohort studies of transient ischaemic attack done in Asia, Europe, and the USA, with early brain and vascular imaging and follow up. All patients were assessed by stroke specialists in hospital settings as inpatients, in emergency departments, or in transient ischaemic attack clinics. Inclusion criteria were stroke-specialist confirmed transient ischaemic attack, age of 18 years or older, and MRI done within 7 days of index transient ischaemic attack and before stroke recurrence. Multivariable logistic regression was done to analyse the predictive utility of abnormal diffusion-weighted MRI, carotid stenosis, and transient ischaemic attack within 1 week of index transient ischaemic attack (dual transient ischaemic attack) after adjusting for ABCD2 score. We compared the prognostic utility of the ABCD2, ABCD2-I, and ABCD3-I scores using discrimination, calibration, and risk reclassification. In 2176 patients from 16 cohort studies done between 2005 and 2015, after adjusting for ABCD2 score, positive diffusion-weighted imaging (odds ratio [OR] 3·8, 95% CI 2·1-7·0), dual transient ischaemic attack (OR 3·3, 95% CI 1·8-5·8), and ipsilateral carotid stenosis (OR 4·7, 95% CI 2·6-8·6) were associated with 7 day stroke after index transient ischaemic attack (p<0·001 for all). 7 day stroke risk increased with increasing ABCD2-I and ABCD3-I scores (both p<0·001). Discrimination to identify early stroke risk was improved for ABCD2-I versus ABCD2 (2 day c statistic 0·74 vs 0·64; p=0·006). However, discrimination was further improved by ABCD3-I compared with ABCD2 (2 day c statistic 0·84 vs 0·64; p<0·001) and ABCD2-I (c statistic 0·84 vs 0·74; p<0·001). Early stroke risk reclassification was improved by ABCD3-I compared with ABCD2-I score (clinical net reclassification improvement 33% at 2 days). Although ABCD2-I and ABCD3-I showed validity, the ABCD3-I score reliably identified highest-risk patients at highest risk of a stroke after transient ischaemic attack with improved risk prediction compared with ABCD2-I. Transient ischaemic attack management guided by ABCD3-I with immediate stroke-specialist assessment, urgent MRI, and vascular imaging should now be considered, with monitoring of safety and cost-effectiveness. Health Research Board of Ireland, Irish Heart Foundation, Irish Health Service Executive, Irish National Lottery, National Medical Research Council of Singapore, Swiss National Science Foundation, Bangerter-Rhyner Foundation, Swiss National Science Foundation, Swisslife Jubiläumsstiftung for Medical Research, Swiss Neurological Society, Fondazione Dr Ettore Balli (Switzerland), Clinical Trial Unit of University of Bern, South Korea's Ministry for Health, Welfare, and Family Affairs, UK Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre.

Abstract S1-03: Pooled individual patient data analysis of stromal tumor infiltrating lymphocytes in primary triple negative breast cancer treated with anthracycline-based chemotherapy

Abstract Background: Retrospective analyses from individual clinical trials have suggested that host anti-tumor immunity as measured by stromal tumor infiltrating lymphocytes (TILs) is important for the outcomes of the primary triple negative breast cancer (TNBC) subgroup, but the clinical utility of TILs in day-to-day management of primary TNBC is still limited. Our objective was to conduct a pooled analysis of the clinical trials that have investigated TILs in TNBC patients treated by anthracyclines-based (A) chemotherapy regimens in order to gain a robust understanding of the prognostic value of TILs in this setting. Material and methods: Methods were predefined in a protocol. Eligible studies were randomized clinical trials that have evaluated the prognostic associations of TILs (evaluated in the same manner) in patients diagnosed with early stage TNBC treated with A or A plus taxanes (A+T). Cox regression models stratified by trial for invasive disease-free survival (IDFS, primary endpoint) and overall survival (OS), fitting stromal TILs as a continuous variable. Results: We collected individual data from 991 TNBC patients included in 6 randomized clinical trials (ECOG2197, ECOG1199, BIG2-98, FinHER, 2 from Gustave Roussy): 62% of patients were treated by A+T and 38% by A alone; 32% of patients had no nodal involvement, 43% of patients had 1-3 nodes and 25% patients more than 3 nodes involved. The average age was 49 years (range 22.6-85 yrs) and the average tumor size 3.0 cm (sd 1.7). Across the entire data set, the average value of stromal TILs was 20% (sd 17%); 90% of patients had at least 1% stromal TILs. After adjusting for trial, stromal TILs were significantly lower with increasing tumor size (linear model, p&amp;lt;0.0001) but not significantly associated with nodal status categories (p=0.52 and p=0.37) nor age (p=0.25). With a median follow-up of 6.6 years for IDFS and 7.3 years for OS, a total of 363 IDFS events and 273 deaths were observed. Each 10% increase in stromal TILs was associated with a 14% relative reduction in IDFS events (HR=0.86, 95% 0.80 to 0.93, p&amp;lt;0.0001) and a 17% relative reduction in deaths (HR=0.83, 95% CI 0.76 to 0.91, p=0.0001). There was no significant evidence for heterogeneity between trials for IDFS (chi2=4.55, p=0.34) nor for OS (chi2=4.45, p=0.34). In a multivariable analysis adjusted for age, nodal status, tumor size and chemotherapy regimen, stromal TILs added significant independent prognostic information for both IDFS and OS (likelihood chi2=17.9 for IDFS, p&amp;lt;0.0001 and chi2=16.7 for OS, p&amp;lt;0.0001). The adjusted hazard ratio for each 10% increase in stromal TILs was HR=0.86 (0.76-0.92) for IDFS events and HR=0.84 (0.76-0.92) for death. Conclusion: This large pooled individual patient data analysis confirms the strong prognostic role of stromal TILS in primary TNBC treated with A or A+T. TILs should now be strongly considered for incorporation as a stratification factor in future clinical trials enrolling TNBC patients. Given the important prognostic role of pre-existing immunity, patients with TNBC are rational candidates for immunotherapy clinical trials. Funding:Ligue Nationale Contre le Cancer. Citation Format: Loi S, Drubay D, Adams S, Francis PA, Joensuu H, Dieci MV, Badve S, Demaria S, Gray R, Piccart MJ, Kellokumpa-Lehtinen P-L, Andre F, Dufaure-Gare I, Denkert C, Salgado R, Michiels S. Pooled individual patient data analysis of stromal tumor infiltrating lymphocytes in primary triple negative breast cancer treated with anthracycline-based chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S1-03.

Serum potassium decline during hospitalization for acute decompensated heart failure is a predictor of 6-month mortality, independent of N-terminal pro–B-type natriuretic peptide levels: An individual patient data analysis

Limited data exist for the role of serum potassium changes during hospitalization for acute decompensated heart failure (ADHF). The present study investigated the long-term prognostic value of potassium changes during hospitalization in patients admitted for ADHF. Our study is a pooled individual patient data analysis assembled from 3 prospective cohorts comprising 754 patients hospitalized for ADHF. The endpoint was all-cause mortality within 180 days after discharge. Serum potassium levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission and at discharge. A percentage decrease >15% in serum potassium levels occurred in 96 (13%) patients, and an absolute decrease of >0.7 mmol/L in serum potassium levels occurred in 85 (12%) patients; and both were predictors of poor outcome independent of admission or discharge serum potassium. After the addition of other strong predictors of mortality-a 30% change in NT-proBNP during hospitalization, discharge levels of NT-proBNP, renal markers, and other relevant clinical variables-the multivariate hazard ratio of serum potassium percentage reduction of >15% remained an independent predictor of 180-day mortality (hazard ratio 2.06, 95% CI 1.14-3.73). A percentage serum potassium decline of >15% is an independent predictor of 180-day all-cause mortality on top of baseline potassium levels, NT-proBNP levels, renal variables, and other relevant clinical variables. This suggest that patients hospitalized for ADHF with a decline of >15% in serum potassium levels are at risk and thus monitoring and regulating of serum potassium level during hospitalization are needed in these patients.

Metastatic involvement of the pituitary gland: a systematic review with pooled individual patient data analysis

To report a rare case of pituitary metastasis (PM) from hepatocellular carcinoma (HCC) and help better understand the incidence of PM and its most common presenting symptoms through a pooled individual patient data analysis. Literature regarding PM was systematically reviewed with a pooled individual patient data analysis conducted. Pooled individual data analysis result is also compared with the result in a most recent systematic review. Our results demonstrate that the incidence of PM among all intracranial metastases is 0.87% (95% CI 0.56, 1.18); it is 1.9% (95% CI 1.46, 2.34) among all autopsied cancer cases; it is 11.56% (95% CI 7.08, 16.04) among all breast cancer patients who had hypophysectomies and 12.83% (95% CI 10.5, 15.16) among all autopsied breast cancer patients. The fixed effect model showed that the incidence of PM in breast cancer patients group is significantly higher (p < 0.001) with an odds ratio of 6.71 (95% CI 4.24, 10.61). Breast and lung cancer are the most common primary cancer of PM with a percentage of 37.2 and 24.2 respectively. The next most common primary sites are prostate and kidney respectively, although the percentages for each are only about 5. Diabetes insipidus (DI) remains the most common symptom among all reported PM cases with a pooled incidence of 42.34% (95% CI 36.15, 48.53). Although not significant (χ(2) = 2.846, df = 1, p = 0.061), it is less common in the most recent reported cases which has a pooled incidence of 32.76% (95% CI 20.31, 45.21). DI is extremely rare in the reported PM cases from HCC (none of the eight cases presented with DI). The symptoms of anterior hypopituitarism (23.68 vs 39.66%, p = 0.015), visual deterioration (27.89 vs 41.38%, p = 0.039), cranial nerve palsies (21.58 vs 41.38%, p = 0.003) and headaches (15.79 vs 32.76%, p = 0.005) were reported significantly higher than previously described in the literature. Pituitary metastasis is rare in patients with cancer, and the pituitary gland is an uncommonly involved location in patients with intracranial metastases. With advanced diagnostic imaging techniques and increased awareness about the manifestation of sellar lesions, the incidence of cranial nerve palsies and anterior pituitarism are higher than reported. This information may allow earlier diagnosis of PM.

Thalidomide in Myelofibrosis with Myeloid Metaplasia: A Pooled-analysis of Individual Patient Data from Five Studies

Trials to determine the effect of thalidomide in patients with Myelofibrosis with Myeloid Metaplasia (MMM) have produced inconclusive results due to different criteria for response and heterogeneous study participants. We undertook a pooled-analysis to assess the effects of such treatment on a larger series of cases and with a uniform assessment of response. We used updated data on 62 individual patients from 5 phase II trials that evaluated thalidomide therapy in MMM patients. Response was judged on individual disease parameters, on the improvement of the Dupriez risk categories and on the improvement of a 6 point "severity score" based on myeloproliferative and myelodepletive indexes of the disease. Overall, using standard dose of thalidomide, i.e. starting with no less than 100 mg/day, 49 patients (79%) had more than 4 weeks of therapy. Twenty-nine percent of patients with moderate to severe anemia showed an increase in hemoglobin or reduction/abolishment of blood transfusion requirements, 38% with moderate to severe thrombocytopenia had an increase in platelet counts, and 41% with high grade splenomegaly demonstrated a measurable reduction in splenic size. These effects led to an absolute decrease in the "severity" score in 44.9% of the patients. Major disease severity and high degrees of splenomegaly before therapy predicted response with a probability of 61.9%. However, worsening of the "severity" score was observed in 20.4% of the patients, 18% having a "myeloproliferative reaction" with leukocytosis and/or thrombocytosis. Sixty-six percent of the patients discontinued the drug before 6 months of treatment due to intolerance. In conclusion, there is a small but clear improvement of disease severity with thalidomide therapy in MMM. The potential for myeloproliferative reactions and the unfavorable dose-related toxicity profile argue for future studies using lower doses of this drug.