Detailed Analysis Of Outcomes Research Articles

Benchmarks for Pediatric Surgical Registries: Recommendations for the Assessment and Grading of Complications.

Procedure-related registries in general surgical practice offer a platform for prospective trials, the pooling of data, and detailed outcome analysis. Recommendations by the Idea, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) collaboration and Outcome4Medicine have further improved the uniform reporting of complications and adverse events.In the pediatric surgical network, disease-specific registries for rare and inherited congenital anomalies are gaining importance, fostering international collaborations on studies of low-incidence diseases. However, to date, reporting of complications in the pediatric surgical registries has been inconsistent. Therefore, the European Reference Network for Rare Inherited and Congenital Anomalies (ERNICA) recently endorsed the validation of the first severity grading system for children. The planned reform of the European Paediatric Surgical Audit (EPSA) registry, which includes the implementation of the Clavien-Madadi classification, represents a further effort to establish uniform outcome reporting.This article provides an overview of experiences with surgical registries and complication reporting, along with the potential application of this knowledge to future pediatric surgical practice.

INFERIOR OUTCOMES WITH POLATUZUMAB VEDOTIN, BENDAMUSTINE AND RITUXIMAB FOR TREATMENT OF RELAPSED/REFRACTORY LARGE B‐CELL LYMPHOMA AFTER >1 PRIOR LINE OF THERAPY

In the pivotal trial, the addition of polatuzumab vedotin to bendamustine and rituximab (Pola-BR) improved overall survival (OS) for stem cell transplant (SCT)-ineligible patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). However, the optimal position of Pola-BR in the treatment pathway for patients who receive it as a ‘stand-alone’ treatment, without planned SCT consolidation or CAR T-cell therapy, remains an open question. 71% of patients in the pivotal trial received Pola-BR in 3rd line or beyond but detailed analysis of outcomes by lines of therapy were not presented and published real-world data for this cohort are lacking. We previously reported results of our real-world study of Pola-BR and we now present further analysis of efficacy according to prior treatment exposure. Methods: Retrospective data were collected for consecutive patients treated with Pola-BR at 28 UK hospitals via the UK Regulatory Agency’s Early Access to Medicines Scheme (EAMS) which ran from June 2019 to Jan 2020 prior to marketing authorisation. Patients with R/R LBCL after ≥1 prior treatment were eligible. Treatment was administered according to the marketing authorisation, dose reductions or delays were permitted according to physicians’ discretion. Responses were investigator assessed, time to event was measured from the start of Pola-BR. Results: Pola-BR was administered as stand-alone treatment for 76 of 106 patients who received it via EAMS, treatment intent for the remaining patients was bridge to CAR-T or SCT. Of the stand-alone cohort, 43 received it 2nd line (2L) and 33 at 3rd line or later (≥3L). The median age was 75 years (range 41-88), 71.1% were male. Patients in the ≥3L group were younger and tended to have later stage disease, other characteristics including sex, performance status, IPI and the presence of bulk were well balanced between the groups. 55.8% and 57.6% respectively, were refractory to their last treatment. The objective response rates (ORR) were 73.2% (95% CI 57.1–85.8) and 54.5% (95% CI 36.4%-71.9%) for the 2L and ≥3L groups respectively (p = 0.1). The complete response (CR) rates were 48.8% (32.9–64.9) and 30.3% (15.6-48.7) (p = 0.1). A best response of progressive disease to Pola-BR was found for 22.0% and 36.4% in the 2L and ≥3L groups respectively. The 6-month progression free survival (PFS) rates were 54.2% (95% CI 37.9–67.9) and 35.9% (95% CI 20.1–52.0) for the 2L and ≥3L groups respectively (HR 2.17 (95% CI 1.19–3.95), p = 0.01). The 6-month OS rate was 68.4% (95% CI 51.8–80.4) in the 2L group and 49.2% (95% CI 30.9–65.2) in the ≥3L group (HR 2.15 (95% CI 1.12–4.14), p = 0.02). Longer follow up will be presented. Keywords: aggressive B-cell non-Hodgkin lymphoma, combination therapies Conflicts of interests pertinent to the abstract W. Osborne Honoraria: Roche R. Auer Honoraria: Beigene C. Burton Honoraria: Roche A. Davies Consultant or advisory role: Celgene, Roche, Gilead, Incyte, Abbvie Honoraria: Celgene, Roche, Gilead, Janssen, Acerta Pharma/AstraZeneca, ADC Therapeutics, Incyte, Abbvie Research funding: Celgene, Roche, Gilead, Janssen, Acerta Pharma/AstraZeneca, ADC Therapeutics, BioInvent Educational grants: Celgene, Roche D. El-Sharkawi Honoraria: Roche Educational grants: Roche C. Fox Consultant or advisory role: Abbvie, AstraZeneca, Atarabio, BMS, GenMab, Gilead/Kite, Incyte, Lilly, Morphosys, Ono, Roche, Takeda Research funding: Beigene Educational grants: Roche, BMS A. Kuhnl Consultant or advisory role: Kite/Gilead, Novartis, BMS Honoraria: Kite/Gilead, Novartis, BMS P. McKay Honoraria: Roche E. Phillips Honoraria: Takeda, Gilead Educational grants: Celgene, Takeda, Janssen W. Townsend Consultant or advisory role: Roche, Takeda, Gilead, Incyte, Honoraria: Roche, Gilead, Incyte Educational grants: Roche, Takeda

Impact of Graft Strategies on the Outcome of Octogenarians Undergoing Coronary Artery Bypass Grafting.

To analyse the outcome of coronary artery bypass grafting (CABG) in octogenarians with coronary multivessel disease and the impact of different graft strategies and other factors. Out of 1654 patients with multivessel disease who underwent CABG at our institution between January 2014 and March 2020, we investigated 225 consecutive patients with a median age of 82.1 years for survival prediction and need for coronary reintervention; a detailed outcome analysis was performed. At mean follow-up of 3.3 years, the overall survival was 76.4%. An indication for emergency operation (p = 0.002), age (p <0.001), chronic pulmonary disease (p = 0.024), and reduced renal or ventricular function (p <0.001) had the highest impact on limited survival. The combination outcome of survival and coronary reintervention was 1.7-fold improved (p = 0.024) after use of the bilateral internal thoracic artery (BITA) (66.2%). Off-pump CABG (12%) revealed no impact on survival. Smokers showed a poorer outcome (p = 0.004). The logistic European System for Cardiac Operative Risk Evaluation was highly effective for evaluating long-term outcomes (p <0.001). BITA grafting normalizes survival and reveals a better outcome in octogenarians with multivessel disease. However, patients at risk of poorer survival were operated under emergency conditions and those with pulmonary disease and reduced ventricular or renal function.

Clinical relevance of lung transplantation for COVID-19 ARDS: a nationwide study.

BackgroundAlthough the number of lung transplantations (LTx) performed worldwide for coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS) is still low, there is general agreement that this treatment can save a subgroup of the most severely ill patients with irreversible lung damage. However, the true proportion of patients eligible for LTx, the overall outcome and the impact of LTx on the pandemic are unknown.MethodsA retrospective analysis was performed using a nationwide registry of hospitalised patients with confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection admitted between 1 January 2020 and 30 May 2021 in Austria. Patients referred to one of the two Austrian LTx centres were analysed, and grouped into patients accepted and rejected for LTx. Detailed outcome analysis was performed for all patients who received a LTx for post-COVID-19 ARDS and compared with patients who underwent LTx for other indications.ResultsBetween 1 January 2020 and 30 May 2021, 39 485 patients were hospitalised for COVID-19 in Austria. 2323 required mechanical ventilation and 183 received extracorporeal membrane oxygenation (ECMO) support. 106 patients with severe COVID-19 ARDS were referred for LTx. Of these, 19 (18%) underwent LTx. 30-day mortality after LTx was 0% for COVID-19 ARDS transplant recipients. At a median follow-up of 134 (47–450) days, 14 out of 19 patients were alive.ConclusionsEarly referral of ECMO patients to a LTx centre is pivotal in order to select patients eligible for LTx. Transplantation offers excellent midterm outcomes and should be incorporated in the treatment algorithm of post-COVID-19 ARDS.

Abdominal versus robotic sacral colpopexy: A detailed analysis of outcomes.

Although abdominal sacrocolpopexy (ASC) is considered the gold standard for surgical repair of vaginal vault prolapse, the open surgical approach has significant morbidity. We aim to compare anatomic and functional outcomes in women receiving either robotic-assisted sacral colpopexy (RSC) or ASC for post-hysterectomy prolapse. We present a retrospective chart review of all women who underwent ASC and RSC at our institution and had 12-month follow-up (FU). Pelvic organ prolapse quantification (POP-Q) staging was assessed both preoperatively and postoperatively. Perioperative and demographic details were collected from the medical records. One hundred twenty four women underwent RSC (mean age 63, median FU 16 months). Those in the ASC group (n = 144) were statistically younger (mean age 60) and had longer FU (median 60 months). Both median day of successful voiding trial and discharge day significantly favored RSC. There were no Clavien Grade IV/V complications for either procedure and three RSC procedures were converted to ASC. Both approaches were associated with a significant improvement in POP-Q stage at FU, with few women requiring additional surgery. Overall, 76% of women in each group were dry from stress urinary incontinence. Improvement in storage and emptying indices, dyspareunia, and quality of life measures was observed after both approaches. RSC demonstrates good support of significant vaginal vault prolapse at medium term FU, with shorter hospital stays and low complication rates. Close FU after RSC over a longer period will be needed to fully assess durability of both functional and anatomic outcomes.

MS12.03 LC-SCRM-Japan, a Pan-Japan Genetic Screening of Lung Cancer

Recently many actionable driver oncogenes such as EGFR, ALK, RET, ROS1, BRAF and MET have been identified in non-small cell lung cancer (NSCLC). However, most of these driver oncogenes are rare and found in only about 1-2% of lung adenocarcinomas. To develop new molecular targeted agents for rare alterations, efficient genomic screening is needed to identify patients. A nationwide genomic screening platform (LC-SCRUM-Japan) was established to primarily screen for ALK, RET and ROS1 fusions using RT-PCR and FISH in advanced non-squamous NSCLC without EGFR mutations in February 2013. From March 2015, this project was expanded to an academic-industrial collaboration initiative with broader eligibility criteria and tumor samples were analyzed by next-generation sequencing (NGS multiplex analysis with OncomineTM Cancer Research Panel). In addition, non-squamous NSCLC regardless of EGFR mutation status and other histological type of lung cancer including squamous NSCLC and small cell lung cancer (SCLC) were enrolled. Clinical information of all patients have also been collected to generate a clinical-genomic database that enables detailed outcome analysis of the cohort. Since its inception, more than 200 Japanese hospitals participated in this project and 7739 patients were enrolled into LC-SCRUM-Japan. 776 squamous NSCLCs and 823 SCLCs were enrolled. Through this platform, many patients with rare driver oncogenes were identified for approved targeted therapies or successfully enrolled into various clinical trials that have helped develop new targeted agents. Based on our project, crizotinib and dabrafenib/trametinib were approved for ROS1 fusions and BRAF mutation positive lung cancers in Japan, respectively. From December 2017, liquid screening with Guardant 360 (LC-SCRUM-Liquid) was initiated and a large concordance study between tissue and liquid NGS analysis was performed in 2000 patients. Additionally, to identify novel biomarkers for immune checkpoint inhibitors, an immuno-oncology biomarker study (LC-SCRUM-IBIS) was conducted with 1017 patients enrolled from February 2017 to May 2018. PD-L1 assessment by IHC and whole exon sequencing was performed. The LC-SCRUM platform was recently expanded to hospitals in Taiwan and we will expand the collaboration to China and other Southeast Asia to establish an integrated Asia cancer clinical genomic database. Genomic screening in LC-SCRUM has provided clinical value by identifying patients with actionable mutations and has helped accelerate clinical development of novel agents. To continue to elevate the standard of cancer care and treatment options for patients in Asia, we are establishing a high quality platform of genomic screening technologies and a mechanism of collecting clinical data that will help elevate precision medicine and drug development in Asia.

Advanced Age Is Not a Barrier to Total Knee Arthroplasty: A Detailed Analysis of Outcomes and Complications in an Elderly Cohort Compared With Average Age Total Knee Arthroplasty Patients

BackgroundLife expectancy and higher complication rates have made the routine use of total knee arthroplasty (TKA) in elderly patients disputed by some authors. The purpose of this study was to assess patient and implant survivorship, complication and revision rates, and patient-reported outcomes (PROMS) in a cohort of patients aged above 80 years undergoing TKA. A comparison with a propensity matched cohort of patients of average age within our database for TKA was performed. MethodsA retrospective review of prospectively collected data identified 644 patients over the age of 80 years undergoing a TKA within a 14-year period. After calculating the average age of all TKA patients within the reviewed database, a cohort deemed average age was created within 1 standard deviation of the average age and matched using the following criteria: gender, surgeon, diagnosis, procedure type, and year. The primary outcomes were survivorship of the implant and the patient. The secondary outcomes were complications, transfusion rates, discharge destination, and PROMS. ResultsThe revision rate was low for both groups (P = .051). Implant survivorship at 10 years was similar (P = .07). Mortality rate was higher in the elderly (P < .001). General complication rate was higher in the elderly (P = .031). Surgical complications rates were similar (P = .702). The PROMS at final follow-up were 4% lower in the elderly (P < .001). ConclusionTKA in the elderly is a safe procedure. With measures minimizing the perioperative complications and blood loss, the outcome can be expected to be similar to patients of average age. The projected implant and patient survivorship in the elderly cohort is long enough to suggest that TKA in the elderly could have a high impact on remaining quality of life.Level III retrospective study.

Migraine Surgery: An All or Nothing Phenomenon? Prospective Evaluation of Surgical Outcomes.

A detailed analysis of outcomes after migraine surgery suggests an anatomic etiology of pain, such as peripheral nerve compression, in select patients. Historically, surgeons have not played a role in the treatment of migraine. However, a subgroup of patients with extracranial anatomic triggers appear to benefit from surgical intervention. Traditionally, the determination of success or failure of migraine surgery is based on whether there is greater or less than 50% improvement of the migraine headache index (MHI) after surgery. However, in this study, patients either did not respond to treatment (≤5%) or improved completely (≥80%). Detailed analysis is provided of this surprising finding. Subjects completed a prospective migraine questionnaire preoperatively as well as at 3 and 12 months postoperatively. All variables improved significantly from baseline. Interestingly, in 83% of patients, the MHI improved either ≥80% or ≤5%, suggesting a more binary distribution. Only 17% of indices fell in the intermediate (5% to 80%) range. Moreover, 69% of patients had ≥80% improvement resulting in a mean improvement of 96% in this group. The remaining 14% had ≤5% improvement, with an average improvement of 0%. Migraine surgery remains controversial. Traditional conservative therapy targets the central theory of migraine propagation. This study again prospectively demonstrates the efficacy of surgical trigger site deactivation in migraine patients. Patients either failed to improve or improved after surgery, with few intermediate outcomes. The binary distribution of data lends further support to an anatomic etiology of pain, that is, peripheral nerve compression, in select patients.

Resection of complex pancreatic injuries: Benchmarking postoperative morbidity using the Accordion Severity Grading System

Background: This study benchmarked the severity of complications using the Accordion Severity Grading System (ASGS) in patients undergoing resection for severe pancreatic injuries. Methods: A prospective database of 461 patients with pancreatic injuries treated from 1990 to 2015 was reviewed. 130 patients with AAST grade 3, 4 or 5 pancreatic injuries underwent resection (pancreatoduodenectomy (PD) n=20, distal pancreatectomy n=110), including 30 who had damage control laparotomy (DCL) and later definitive surgery. Uni- and multivariate logistic regression analysis was applied. Results: Overall 238 complications occurred in 95 (73%) patients of which 73% were ASGS grades 3-6. 19 patients (14.6%) died. Patients more likely to have complications after pancreatic resection were older, had RTS <7.8, were shocked on admission, had grade 5 pancreatic injuries with vascular and duodenal injuries, required a DCL, received a larger blood transfusion, had a PD and repeat laparotomies. Applying univariate logistic regression analysis, mechanism of injury, RTS <7.8, shock on admission, DCL, increasing AAST grade and type of pancreatic resection were significant variables for complications. Multivariate logistic regression analysis however showed that only age and type of pancreatic resection (PD) were significant. Conclusion: ASGS-assessed morbidity after pancreatic resection for trauma was high. This detailed outcome analysis serves as a reference for future institutional comparisons.

Resection of complex pancreatic injuries: benchmarking postoperative morbidity using the accordion severity grading system

Background: This study benchmarked the severity of complications using the Accordion Severity Grading System (ASGS) in patients undergoing resection for severe pancreatic injuries. Methods: A prospective database of 461 patients with pancreatic injuries treated from 1990 to 2015 was reviewed. 130 patients with AAST grade 3, 4 or 5 pancreatic injuries underwent resection (pancreatoduodenectomy (PD) n=20, distal pancreatectomy n=110), including 30 who had damage control laparotomy (DCL) and later definitive surgery. Uni- and multivariate logistic regression analysis was applied. Results: Overall 238 complications occurred in 95 (73%) patients of which 73% were ASGS grades 3-6. 19 patients (14.6%) died. Patients more likely to have complications after pancreatic resection were older, had RTS <7.8, were shocked on admission, had grade 5 pancreatic injuries with vascular and duodenal injuries, required a DCL, received a larger blood transfusion, had a PD and repeat laparotomies. Applying univariate logistic regression analysis, mechanism of injury, RTS <7.8, shock on admission, DCL, increasing AAST grade and type of pancreatic resection were significant variables for complications. Multivariate logistic regression analysis however showed that only age and type of pancreatic resection (PD) were significant. Conclusion: ASGS-assessed morbidity after pancreatic resection for trauma was high. This detailed outcome analysis serves as a reference for future institutional comparisons.

A WDO Framework for Optimal Deployment of DGs and DSCs in a Radial Distribution System Under Daily Load Pattern to Improve Techno-Economic Benefits

This article presents a methodology to determine optimal locations and sizes of DGs (Distributed Generator) and DSCs (D-STATCOM) simultaneously in a radial distribution network during a daily load pattern to improve the techno-economic benefits. An effective weighted objective function has been designed to address daily power loss minimization of the three techno-economic benefits, improvement of daily voltage profile and maximization of net annual savings due to the placement of DGs and DSCs. A repetitive backward-forward sweep based load flow has been used to calculate the daily power loss and bus voltages. To optimize the designed objective function, an efficient and simple nature-inspired wind driven optimization (WDO) algorithm has been used. To validate the effectiveness of the proposed methodology, different scenarios are considered and a detailed outcome analysis is presented.

Anterior Cervical Decompression and Fusion or Posterior Foraminotomy for Cervical Radiculopathy: Results of a Single-Center Series.

Anterior cervical diskectomy and fusion (ACDF) or posterior foraminotomy (PF) are standard treatment options for cervical radiculopathy due to disk prolapse. Which method produces superior results has not yet been established. One reason for the dilemma, among others, is a lack of detailed outcome analysis in previous studies. We quantified outcome to compare both methods in our retrospective single-center series. We conducted a retrospective analysis of 107 patients with cervical radiculopathy who were operated on via ACDF or via PF. Demographic data, symptoms, neurologic status, and pathology were recorded and correlated to outcome parameters such as Odom's criteria, visual analog scale values of radicular pain, Neck Disability Index values, and subjective satisfaction, which were also compared between both treatment groups. Intraoperative data, early and late complications, and reoperations were recorded and compared between both surgical groups. None of the recorded preoperative data were predictive for postoperative outcome parameters. Patients in the PF group reported better overall outcome (Odom's criteria) and greater relief of radicular and neck pain. Operative time and blood loss were less in the PF group. Both groups showed comparable early complication rates, but PF patients tended to have more late reoperations. Due to a better overall outcome as well as greater relief of radicular and neck pain in our cohort, we consider PF the first-line treatment if morphology of the pathology is suitable.

Resection of complex pancreatic injuries: Benchmarking postoperative complications using the Accordion classification.

AIMTo benchmark severity of complications using the Accordion Severity Grading System (ASGS) in patients undergoing operation for severe pancreatic injuries.METHODSA prospective institutional database of 461 patients with pancreatic injuries treated from 1990 to 2015 was reviewed. One hundred and thirty patients with AAST grade 3, 4 or 5 pancreatic injuries underwent resection (pancreatoduodenectomy, n = 20, distal pancreatectomy, n = 110), including 30 who had an initial damage control laparotomy (DCL) and later definitive surgery. AAST injury grades, type of pancreatic resection, need for DCL and incidence and ASGS severity of complications were assessed. Uni- and multivariate logistic regression analysis was applied.RESULTSOverall 238 complications occurred in 95 (73%) patients of which 73% were ASGS grades 3-6. Nineteen patients (14.6%) died. Patients more likely to have complications after pancreatic resection were older, had a revised trauma score (RTS) < 7.8, were shocked on admission, had grade 5 injuries of the head and neck of the pancreas with associated vascular and duodenal injuries, required a DCL, received a larger blood transfusion, had a pancreatoduodenectomy (PD) and repeat laparotomies. Applying univariate logistic regression analysis, mechanism of injury, RTS < 7.8, shock on admission, DCL, increasing AAST grade and type of pancreatic resection were significant variables for complications. Multivariate logistic regression analysis however showed that only age and type of pancreatic resection (PD) were significant.CONCLUSIONThis ASGS-based study benchmarked postoperative morbidity after pancreatic resection for trauma. The detailed outcome analysis provided may serve as a reference for future institutional comparisons.

Outcome of femoral fractures care as a measure of trauma care between level I and level II trauma systems in Israel

BackgroundOur hypothesis in this study was that the outcome of patients with femur fractures would be favorable in a level I trauma center (LITC).MethodsA prospective multicenter cohort study. 5 LITC...

Efficacy of Topical Timolol as Primary Monotherapy in Cutaneous Facial Infantile Hemangiomas.

Recent studies have shown that infantile hemangiomas (IHs) undergo a rapid growth phase between 5.5 and 7.5 weeks of life and do not usually proliferate beyond 6 months; growth thereafter is usually proportionate to the child's growth. This review assesses the evidence for topical timolol as primary monotherapy for cutaneous facial IHs before 12 months of age, and to determine the differences in outcome between early (before 6 months) and late initiation (after 6 months) of timolol. A review of English language articles published up to November 2015 was performed using selected key words. Articles identified were further reviewed for relevance. The full text of studies included for final analysis was perused to include pertinent patient details, treatment protocol with timolol, complications (if any) reported, and response to treatment. Four studies met the inclusion criteria. In children before 12 months of age, the efficacy of topical timolol for the treatment of cutaneous facial IHs in achieving clinically significant improvement as defined by a standardized Global Assessment Score score of 3 and above ranged from 47% to 88%. One study also showed that IH regression was greater in patients started on timolol before 6 months of age compared with those started later (P <0.05). Topical timolol initiated in children before 12 months of age appears to be safe and clinically effective. There was insufficient data for detailed analysis of outcomes in patients who commenced treatment before and after 6 months of age.

Seventh INTERMACS annual report: 15,000 patients and counting

The seventh annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 9 years of patient enrollment. The Registry includes >15,000 patients from 158 participating hospitals. Trends in device strategy, patient profile at implant and survival are presented. Risk factors for mortality with continuous-flow pumps are updated, and the major causes/modes of death are presented. The adverse event burden is compared between eras, and health-related quality of life is reviewed. A detailed analysis of outcomes after mechanical circulatory support for ambulatory heart failure is presented. Recent summary data from PediMACS and MedaMACS is included. With the current continuous-flow devices, survival at 1 and 2 years is 80% and 70%, respectively.

Embolic Strokes of Undetermined Source in the Athens Stroke Registry: An Outcome Analysis.

Information about outcomes in Embolic Stroke of Undetermined Source (ESUS) patients is unavailable. This study provides a detailed analysis of outcomes of a large ESUS population. Data set was derived from the Athens Stroke Registry. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group criteria. End points were mortality, stroke recurrence, functional outcome, and a composite cardiovascular end point comprising recurrent stroke, myocardial infarction, aortic aneurysm rupture, systemic embolism, or sudden cardiac death. We performed Kaplan-Meier analyses to estimate cumulative probabilities of outcomes by stroke type and Cox-regression to investigate whether stroke type was outcome predictor. 2731 patients were followed-up for a mean of 30.5±24.1months. There were 73 (26.5%) deaths, 60 (21.8%) recurrences, and 78 (28.4%) composite cardiovascular end points in the 275 ESUS patients. The cumulative probability of survival in ESUS was 65.6% (95% confidence intervals [CI], 58.9%-72.2%), significantly higher compared with cardioembolic stroke (38.8%, 95% CI, 34.9%-42.7%). The cumulative probability of stroke recurrence in ESUS was 29.0% (95% CI, 22.3%-35.7%), similar to cardioembolic strokes (26.8%, 95% CI, 22.1%-31.5%), but significantly higher compared with all types of noncardioembolic stroke. One hundred seventy-two (62.5%) ESUS patients had favorable functional outcome compared with 280 (32.2%) in cardioembolic and 303 (60.9%) in large-artery atherosclerotic. ESUS patients had similar risk of composite cardiovascular end point as all other stroke types, with the exception of lacunar strokes, which had significantly lower risk (adjusted hazard ratio, 0.70 [95% CI, 0.52-0.94]). Long-term mortality risk in ESUS is lower compared with cardioembolic strokes, despite similar rates of recurrence and composite cardiovascular end point. Recurrent stroke risk is higher in ESUS than in noncardioembolic strokes.

A detailed analysis of outcome reporting from randomised controlled trials and meta-analyses of inguinal hernia repair.

Evidence is needed to justify whether investment in an internationally agreed core outcome set for inguinal hernia surgery is needed. This study aimed to assess outcome reporting from randomised controlled trials (RCTs) and meta-analyses in inguinal hernia surgery. RCTs and meta-analyses comparing surgical technique or mesh type for primary inguinal hernia repair were systematically identified. Verbatim details, type, frequency and definition of clinician-observed and -assessed outcomes were summarised. Patient-reported outcome measures (PROMs) were analysed for instrument validity and frequency of domain reporting. 40 RCTs (10,810 patients) and 7 meta-analyses (17,280 patients) were identified. No single PROM was reported by all studies. There were 58 different clinician-observed outcomes, with recurrence (n = 47, 100%), wound infection (n = 33, 70.2%), haematoma (n = 31, 77.5%) and seroma formation (n = 22, 46.8%) being most frequently reported. All studies measured patients' views, although only 12 (30.0%) used validated instruments. The SF36 was the most commonly used multi-dimensional valid PROM (n = 7), and a visual analogue scale assessing pain (n = 32) was the most frequently used unidimensional scale. Non-validated questionnaires assessed 25 other aspects of patients' health. Two meta-analyses defined recurrence and three chronic pain although neither ensured that included RCTs adhered to the definitions. Outcome reporting from RCTs concerning inguinal hernia repair is inconsistent and poorly defined, limiting meta-analyses, which themselves do not control for the differing definitions of assessed outcomes. This study justifies investment in a standardised core outcome set for inguinal hernia surgery, to improve outcome reporting and evidence synthesis.

Bortezomib-Thalidomide-Dexamethasone Incorporated Into Autotransplantation Is Associated with More Favorable Outcomes After Relapse in Comparison with Thalidomide-Dexamethasone Plus Autotransplantation in Multiple Myeloma

AbstractAbstract ▪4210▪This icon denotes a clinically relevant abstractIn a previous analysis performed with a median follow-up of 36 months (mos), superior CR/nCR rates and extended PFS were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) vs thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autotransplantation (ASCT) for newly diagnosed myeloma (MM). Here we report an updated analysis of that study, including a detailed analysis of outcomes after relapse or progression (R/P), an important issue for patients (pts) who received up-front a triplet novel agent-based therapy incorporated into ASCT. After a median follow-up of 52 mos, continued TTP and PFS benefits with VTD vs TD were demonstrated, while no difference in OS was seen between the two arms. Median PFS for pts randomized to the VTD arm was 56 mos vs 42 mos for those assigned to TD (HR=0.64, p=0.001). Similarly to PFS, median TTP for pts in the VTD group was longer than in the TD group (57 vs 45 mos, HR=0.63, p=0.0006), reflecting a 37% reduction in the risk of R/P with VTD. The probabilities of R/P in the VTD and TD arms were 41% vs 55% (p=0.002). In comparison with the VTD-treated group, a higher percentage of pts in the TD arm required the immediate start of salvage therapy after symptomatic R/P was documented (67% vs 82.5%). By the opposite, the fraction of pts with asymptomatic R/P that did not require any antimyeloma therapy until the cut-off date for the analysis was higher in the VTD arm compared with the TD-treated group (33% vs 17.5%, p=0.016). In these pts, the median interval from the date of R/P to the cut-off date for the analysis was 7 mos for the TD-treated group vs 17 mos for the VTD-treated group. Median time to subsequent antimyelomatherapy (defined as the interval between start of induction therapy and administration of the first dose of second-line therapy) was significantly longer for pts who experienced R/P in the VTD arm in comparison with pts who progressed in the TD arm (35 vs 29 mos, p=0.018). The associated interval between last administration of front-line therapy (e.g. consolidation for pts who received the entire treatment program or every other treatment before consolidation for those who discontinued earlier) and first administration of second-line therapy (salvage therapy-free interval) was 22.5 mos for the VTD-treated group vs 15 mos for the TD-treated group (p=0.009). Both bortezomib and lenalidomide were the most frequently used agents at the time of R/P (82% of all cases), while only 18% of pts were treated with conventional cytotoxic drugs. As expected, the majority of pts in the TD arm received a second-line therapy that included bortezomib (70%), while lenalidomide-dexamethasone was received by 10% of pts. By the opposite, in the VTD arm both bortezomib- and lenalidomide-based salvage therapies were equally distributed (41% vs 39%). The probability to achieve at least a partial response after second-line therapy including bortezomib was 60% for pts with prior exposure to VTD vs 63% for those randomized to TD. No difference in post-R/P OS was demonstrated between VTD-treated and TD-treated subgroups of pts who received bortezomib-based salvage therapy after R/P (2-yr estimates: 48% vs 53%, p=0.59). In the overall population, post-R/P OS was significantly shorter for pts who received salvage therapy with conventional cytotoxic drugs (2-yr estimate: 41%) in comparison with pts treated with novel agents, including bortezomib or lenalidomide (2-yr estimates: 52% and 53%, respectively) (p=0.0001). In conclusion, front-line therapy with VTD incorporated into ASCT was superior in comparison with TD plus ASCT in terms of extended TTP, PFS, time to subsequent antimyeloma therapy and salvage therapy-free interval. VTD-treated pts had a higher probability than TD-treated pts to experience long-lasting asymptomatic R/P not requiring second-line therapy. VTD-treated and TD-treated pts who subsequently received bortezomib-based salvage therapies had similar rates of response and post-R/P OS. This finding suggests that short-term exposure to VTD, as planned in our study, did not favor the selection of bortezomib-resistant clones, thus allowing to rechallenge bortezomib as (part of) second-line therapy after symptomatic R/P. Disclosures:Cavo:Janssen, Celgene, Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria. Di Raimondo:Celgene, Janssen: Honoraria, Speakers Bureau. Offidani:Janssen, Celgene: Honoraria. Caravita:Celgene, Janssen, Novartis, Genzyme: Honoraria. Boccadoro:Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Detailed long-term outcome analysis after decompressive craniectomy for severe traumatic brain injury

Objective: To assess detailed long-term clinical outcome at least 1 year after decompressive craniectomy (DC) in patients with severe traumatic brain injury (TBI).Methods: One hundred and thirty-one patients with severe TBI underwent DC between September 1997 and September 2005. Outcome was measured using the Glasgow Outcome Scale (GOS). Detailed outcome analysis was performed using Glasgow Outcome Scale Extended, Short-Form 36 (SF-36), Beck Depression Inventory, Trail Making Test B (TMT-B), Digit-Symbol Test (DST) and Barthel Index (BI).Results: Sixty-three patients (48.1%) died during their initial hospital stay, 27 (20.6%) were discharged in a vegetative state, 32 (24.4%) with severe disability and nine (6.9%) with moderate disability (GOS 3 and 4, respectively). At time of follow-up 75 patients (67.7%) were either dead or in a vegetative state. Thirty patients with GOS >2 were recruited for a detailed outcome analysis: Major depression, neurologic deficits and impaired TMT-B and DST performances were common and significantly more prevalent than in normative controls. Yet, patients reported only modestly reduced SF-36 and high BI scores.Conclusions: Despite multiple health-related problems after DC, many patients proved highly functional in activities of daily living and reported qualities of life not significantly inferior to that of healthy individuals. Depression was common and requires to be addressed with patients and caregivers. Better targeted therapies could improve neuropsychological and psychiatric outcomes in this complex cohort.