How I do it: percutaneous transforaminal endoscopic discectomy for lumbar disk herniation

Background: Percutaneous transforaminal endoscopic discectomy (PTED) has emerged as a less invasive technique to treat symptomatic lumbar disk herniation (LDH). PTED is performed under local anesthesia with the advantage of immediate intraoperative feedback of the patient. In this paper, the technique is described as conducted in our hospital. Methods: PTED is performed under local anesthesia in prone position on thoracopelvic supports. The procedure is explained stepwise: e.g. marking, incision, introduction of the 18-gauge needle and guidewire to the superior articular process, introduction of the TomShidi needle and foraminotomy up to 9 mm, with subsequently removal of di

Full endoscopic versus open discectomy for sciatica:randomised controlled non-inferiority trial

OBJECTIVE: To assess whether percutaneous transforaminal endoscopic discectomy (PTED) is non-inferior to conventional open microdiscectomy in reduction of leg pain caused by lumbar disc herniation. DESIGN: Multicentre randomised controlled trial with non-inferiority design. SETTING: Four hospitals in the Netherlands. PARTICIPANTS: 613 patients aged 18-70 years with at least six weeks of radiating leg pain caused by lumbar disc herniation. The trial included a predetermined set of 125 patients receiving PTED who were the learning curve cases performed by surgeons who did not do PTED before the trial. INTERVENTIONS: PTED (n=179) compared with open microdiscectomy (n=309). MAIN OUTCOME MEASURES: The primary outcome was self-reported leg pain measured by a 0-100 visual analogue scale at 12 months, assuming a non-inferiority margin of 5.0. Secondary outcomes included complications, reoperations, self-reported functional status as measured with the Oswestry Disability Index, visual analogue scale for back pain, health related quality of life, and self-perceived recovery. Outcomes were measured until one year after surgery and were longitudinally analysed according to the intention-to-treat principle. Patients belonging to the PTED learning curve were omitted from the primary analyses. RESULTS: At 12 months, patients who were randomised to PTED had a statistically significantly lower visual analogue scale score for leg pain (median 7.0, interquartile range 1.0-30.0) compared with patients randomised to open microdiscectomy (16.0, 2.0-53.5) (between group difference of 7.1, 95% confidence interval 2.8 to 11.3). Blood loss was less, length of hospital admission was shorter, and timing of postoperative mobilisation was earlier in the PTED group than in the open microdiscectomy group. Secondary patient reported outcomes such as the Oswestry Disability Index, visual analogue scale for back pain, health related quality of life, and self-perceived recovery, were similarly in favour of PTED. Within one year, nine (5%) in the PTED group compared with 14 (6%) in the open microdiscectomy group had repeated surgery. Per protocol analysis and sensitivity analyses including the patients of the learning curve resulted in similar outcomes to the primary analysis. CONCLUSIONS: PTED was non-inferior to open microdiscectomy in reduction of leg pain. PTED resulted in more favourable results for self-reported leg pain, back pain, functional status, quality of life, and recovery. These differences, however, were small and may not reach clinical relevance. PTED can be considered as an effective alternative to open microdiscectomy in treating sciatica. TRIAL REGISTRATION: NCT02602093ClinicalTrials.gov NCT02602093

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Body Image and Cosmesis after Percutaneous Transforaminal Endoscopic Discectomy versus Conventional Open Microdiscectomy for Sciatica

Study Design: Randomized controlled trial Objective: Percutaneous transforaminal endoscopic discectomy (PTED) was introduced as a less invasive procedure to treat sciatica. Even though the PTED has a small scar size, it is unknown if PTED also leads to better scar-related patient-reported outcomes. Therefore, we aimed to compare scar-related outcomes between patients undergoing PTED vs open microdiscectomy. Methods: Patients with at least 6 weeks of radiating leg pain were randomized in a 1:1 ratio to PTED or open microdiscectomy. Scar-related patient-reported outcomes were measured using the Body Image Score (BIS), Cosmesis Scale (CS) and a 0-10 numeric rating scale (NRS) on scar esthetic. Results: Of the 530 included patients, 286 patients underwent PTED and 244 underwent open microdiscectomy as allocated. At 12 months of follow-up, 95% of the patients had data available. At 12 months, the BIS was 6.2 ± 1.7 in the PTED-group and 6.6 ± 1.9 in the open microdiscectomy group (between-group difference.4, 95% CI.2 to.7). CS was 21.3 ± 3.0 in the PTED-group and 18.6 ± 3.4 in the open microdiscectomy group (between-group difference −2.7, 95% CI −3.1 to −2.3). Average NRS for scar esthetic was 9.2 ± 1.3 and 7.8 ± 1.6 in the PTED and open microdiscectomy groups, respectively (between-group difference −1.4, 95% CI −1.6 to −1.2) Conclusions: PTED leads to a higher self-rated scar esthetic as compared to open microdiscectomy, while self-reported body image seems to be comparable between both groups. Therefore, from an esthetic point, PTED seems to be the preferred technique to treat sciatica.</p

Surgeons Learning Curve of Transforaminal Endoscopic Discectomy for Sciatica

Objective: Full-endoscopic spine surgery is gaining interest as a less-invasive alternative to treat sciatica caused by a lumbar disc herniation. Concerns, however, exist with the learning curve as percutaneous transforaminal endoscopic discectomy (PTED) appears to be more difficult to be performed compared to other techniques. In this study, the clinical outcomes during and after the learning curve are presented of 3 surgeons naïve to PTED. Methods: In the first phase of a randomized controlled, noninferiority trial comparing PTED with microdiscectomy, 3 surgeons were trained in the PTED-procedure by a senior surgeon. After performing up to 20 cases under supervision, they started performing PTED on their own. Results of the early cases were compared to the later cases (>20). Further-more, complications and reoperations were compared. Finally, differences in clinical outcomes between surgeons were compared. Results: At 12 months of follow-up, 87% of the patients had follow-up data available. In general, there were no significant differences in patient-reported outcomes between the early and later PTED cases. Furthermore, outcomes of the early PTED cases were comparable to the outcomes of microdiscectomy, while the later PTED cases had small, but more favorable outcomes compared to microdiscectomy. Two learning curve surgeons had substantially higher rates of reoperations within 1 year, compared to the senior surgeon or the microdiscectomy group. Duration of surgery was also longer for all learning curve surgeons. Finally, when comparing clinical outcomes of patients undergoing PTED versus microdiscectomy, there appears to be some statistically significant differences in outcomes compared between the senior and 3 learning curve surgeons. Conclusion: PTED appears to be safe to be adopted by surgeons naïve to the procedure when they are initially supervised by an experienced senior surgeon. Duration of surgery and risk of repeated surgery are increased during the learning curve, but patient-reported outcomes of the early PTED cases are similar to the outcomes of later PTED cases, and similar to the outcomes of microdiscectomy cases. This study underlines the need for an experienced mentor for surgeons to safely adopt PTED

Single-arm, open-label, multicentre first in human study to evaluate the safety and performance of dural sealant patch in reducing CSF leakage following elective cranial surgery: the ENCASE trial

OBJECTIVE: The dural sealant patch (DSP) is designed for watertight dural closure after cranial surgery. The goal of this study is to assess, for the first time, safety and performance of the DSP as a means of reducing cerebrospinal fluid (CSF) leakage in patients undergoing elective cranial intradural surgery with a dural closure procedure. DESIGN: First in human, open-label, single-arm, multicentre study with 360-day (12 months) follow-up. SETTING: Three large tertiary reference neurosurgical centres, two in the Netherlands and one in Switzerland. PARTICIPANTS: Forty patients undergoing elective cranial neurosurgical procedures, stratified into 34 supratentorial and six infratentorial trepanations. INTERVENTION: Each patient received one DSP after cranial surgery and closure of the dura mater with sutures. OUTCOME MEASURES: Primary composite endpoint was occurrence of one of the following events: postoperative percutaneous CSF leakage, intraoperative leakage at 20 cm H$_{2}$O positive end-expiratory pressure or postoperative wound infection. Overall success was defined as achieving the primary endpoint in no more than two patients. Secondary endpoints were device-related serious adverse events or adverse events (AEs), pseudomeningocele and thickness of dura+DSP. Additional endpoints were reoperation in 30 days and user satisfaction. RESULTS: No patients met the primary endpoint. No device-related (serious) AEs were observed. There were two incidences of self-limiting pseudomeningocele as confirmed on MRI. Thickness of dura and DSP were (mean±SD) 3.5 mm±2.0 at day 7 and 2.1 mm±1.2 at day 90. No patients were reoperated within 30 days. Users reported a satisfactory design and intuitive application. CONCLUSIONS: DSP, later officially named Liqoseal, is a safe and potentially efficacious device for reducing CSF leakage after intracranial surgery, with favourable clinical handling characteristics. A randomised controlled trial is needed to assess Liqoseal efficacy against the best current practice for reducing postoperative CSF leakage. TRIAL REGISTRATION NUMBER: NCT03566602