To determine the long-term effects of ranibizumab (RBZ) in patients with diabetic macular edema (DME).
Prospective, randomized, interventional, multicenter clinical trial.
One hundred twenty-six ...patients with DME.
Subjects were randomized 1:1:1 to receive 0.5 mg RBZ at baseline and months 1, 3, and 5 (group 1), focal or grid laser photocoagulation at baseline and month 3 if needed (group 2), or a combination of 0.5 mg RBZ and focal or grid laser at baseline and month 3 (group 3). Starting at month 6, if retreatment criteria were met, all subjects could be treated with RBZ.
The mean change from baseline in best-corrected visual acuity (BCVA) at month 24.
After the primary end point at month 6, most patients in all groups were treated only with RBZ, and the mean number of injections was 5.3, 4.4, and 2.9 during the 18-month follow-up period in groups 1, 2, and 3, respectively. For the 33 patients in group 1, 34 patients in group 2, and 34 patients in group 3 who remained in the study through 24 months, the mean improvement in BCVA was 7.4, 0.5, and 3.8 letters at the 6-month primary end point, compared with 7.7, 5.1, and 6.8 letters at month 24, and the percentage of patients who gained 3 lines or more of BCVA was 21, 0, and 6 at month 6, compared with 24, 18, and 26 at month 24. The percentage of patients with 20/40 or better Snellen equivalent at month 24 was 45% in group 1, 44% in group 2, and 35% in group 3. Mean foveal thickness (FTH), defined as center subfield thickness, at month 24 was 340 μm, 286 μm, and 258 μm for groups 1, 2, and 3, respectively, and the percentage of patients with center subfield thickness of 250 μm or less was 36%, 47%, and 68%, respectively.
Intraocular injections of RBZ provided benefit for patients with DME for at least 2 years, and when combined with focal or grid laser treatments, the amount of residual edema was reduced, as were the frequency of injections needed to control edema.
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Abstract Purpose Magnetic resonance image guided radiation therapy (MR-IGRT) has been used at our institution since 2014. We report on more than 2 years of clinical experience in treating patients ...with the world's first MR-IGRT system. Methods and materials A clinical service was opened for MR-IGRT in January 2014 with an MR-IGRT system consisting of a split 0.35T magnetic resonance scanner that straddles a ring gantry with 3 multileaf collimator-equipped60 Co heads. The service was expanded to include online adaptive radiation therapy (ART) MR-IGRT and cine gating after 6 and 9 months, respectively. Patients selected for MR-IGRT were enrolled in a prospective registry between January 2014 and June 2016. Patients were treated with a variety of radiation therapy techniques including intensity modulated radiation therapy and stereotactic body radiation therapy (SBRT). When applicable, online ART was performed and gating on sagittal 2-dimensional cine MR was used. The charts of patients treated with MR-IGRT were reviewed to report on the clinical and treatment characteristics of the initial patients who were treated with this novel technique. Results A total of 316 patients have been treated with the MR-IGRT system, which has been integrated into a high-volume clinic. The cases were most commonly selected for improved soft tissue visualization, ART, and cine gating. Seventy-six patients were treated with 3-dimensional conformal radiation therapy, 146 patients with intensity modulated radiation therapy, and 94 patients with SBRT. The most commonly treated disease sites were the abdomen (28%), breast (26%), pelvis (22%), thorax (19%), and head and neck (5%). Sixty-seven patients were treated with online ART over a total of 244 adapted fractions. Cine treatment gating was used for a total of 81 patients. Conclusions MR-IGRT has been successfully implemented in a high-volume radiation clinic and provides unique advantages in the treatment of a variety of malignancies. Additional clinical trials are in development to formally evaluate MR-IGRT in the treatment of multiple disease sites with techniques such as SBRT and ART.
To assess safety, technical success, local control, and survival associated with percutaneous image-guided adrenal ablation.
Adult patients with adrenal metastases who underwent percutaneous ...image-guided adrenal ablation during the years 2003-2012 were identified. There were 32 patients with 37 adrenal tumors identified. Technical success, safety, local control, and survival were analyzed according to standard criteria.
In 32 patients (25 men and 7 women; mean age, 66 y; age range, 44-88 y) with 37 adrenal tumors, 35 ablation procedures were performed. One patient with an 8.2-cm tumor underwent planned cryoablation debulking fully anticipating untreated margins owing to close proximity of the pancreas (ie, the intent was to diminish tumor burden rather than a curative intervention). Of the 36 patients treated with curative intent, technical success was achieved in 35 (97%) tumors. Follow-up imaging was performed on 34 of 37 tumors (excluding patients with intentional debulking n = 1, technical failure n = 1, and absence of follow-up n = 1). Local recurrence developed in 3 (8.8%) of 34 tumors. Local tumor control was achieved in 31 lesions at a mean of 22.7 months of follow-up. Recurrence-free survival and overall survival at 36 months were 88% and 52%, respectively, with a median survival of 34.5 months. A Common Terminology Criteria for Adverse Events version 4 grade 3 or 4 complication was observed in three (8.6%) ablation procedures.
Image-guided ablation is safe and effective for local control of metastatic adrenal tumors and provides a minimally invasive alternative to surgical resection in appropriately selected patients.
Abstract Background Context Numerous studies have demonstrated poorer outcomes in patients with Workers' compensation (WC) when compared with those without WC following treatment of various of health ...conditions, including spine disorders. It is thus important to consider compensation status when assessing treatment outcomes in spine surgery. However, reported strengths of association have varied significantly (1.31–7.22). Purpose The objective of this study was to evaluate the association of unsatisfactory outcomes on compensation status in spine surgery patients. Study Design/Setting A meta-analysis was performed. Patient Sample Patient sample is not applicable in this study. Outcome Measure Demographics, type of surgery, country, follow-up time, patient satisfaction, return to work and non-union events were the outcome measures. Methods Both prospective and retrospective studies that compared outcomes between compensated and non-compensated patients in spine surgery were included. Two independent investigators extracted outcome data. The meta-analysis was performed using Revman software. Random effects model was used to calculate risk ratio (RR, 95% confidence interval CI) for dichotomous variables. Results Thirty-one studies (13 prospective; 18 retrospective) with a total of 3,567 patients were included in the analysis. Follow-up time varied from 4 months to 10 years. Twelve studies involved only decompression; the rest were fusion. Overall RR of an unsatisfactory outcome was 2.12 1.74, 2.58; p<.001 in patients with WC when compared with those without WC after surgery. The RR ofan unsatisfactory outcome in patients with WC, compared with those without, was 2.09 1.38, 3.17; p<.01 among studies from Europe and Australia, and 2.14 1.48, 2.60; p<.01 among US studies. The RR of decompression-only procedures was 2.53 1.85, 3.47; p<.01,and 1.79 1.45, 2.21; p<.01 for fusion. Forty-three percent (209 of 491) of patients with WC did not return to work versus 17% (214 of 1250) of those without WC (RR 2.07 1.43, 2.98; p<.001). Twenty-five percent (74 of 292) and 13.5% (39 of 287) of patients had non-union in the compensated and non-compensated groups, respectively. This was not statistically significant (RR 1.33 0.92, 1.91; p=.07). Conclusions Workers' compensation patients have a two-fold increased risk of an unsatisfactory outcome compared with non-compensated patients after surgery. This association was consistent when studies were grouped by country or procedure. Compensation status must be considered in all surgical intervention studies.
OBJECTIVE The incidence of already common chronic subdural hematomas (CSDHs) and other nonacute subdural hematomas (NASHs) in the elderly is expected to rise as the population ages over the coming ...decades. Surgical management is associated with recurrence and exposes elderly patients to perioperative and operative risks. Middle meningeal artery (MMA) embolization offers the potential for a minimally invasive, less morbid treatment in this age group. The clinical and radiographic outcomes after MMA embolization treatment for NASHs have not been adequately described in elderly patients. In this paper, the authors describe the clinical and radiographic outcomes after 151 cases of MMA embolization for NASHs among 121 elderly patients. METHODS In a retrospective review of a prospectively maintained database across 15 US academic centers, the authors identified patients aged ≥ 65 years who underwent MMA embolization for the treatment of NASHs between November 2017 and February 2020. Patient demographics, comorbidities, clinical and radiographic factors, treatment factors, and clinical outcomes were abstracted. Subgroup analysis was performed comparing elderly (age 65–79 years) and advanced elderly (age > 80 years) patients. RESULTS MMA embolization was successfully performed in 98% of NASHs (in 148 of 151 cases) in 121 patients. Seventy elderly patients underwent 87 embolization procedures, and 51 advanced elderly patients underwent 64 embolization procedures. Elderly and advanced elderly patients had similar rates of embolization for upfront (46% vs 61%), recurrent (39% vs 33%), and prophylactic (i.e., with concomitant surgical intervention; 15% vs 6%) NASH treatment. Transfemoral access was used in most patients, and the procedure time was approximately 1 hour in both groups. Particle embolization with supplemental coils was most common, used in 51% (44/87) and 44% (28/64) of attempts for the elderly and advanced elderly groups, respectively. NASH thickness decreased significantly from initial thickness to 6 weeks, with additional decrease in thickness observed in both groups at 90 days. At longest follow-up, the treated NASHs had stabilized or improved in 91% and 98% of the elderly and advanced elderly groups, respectively, with > 50% improvement seen in > 60% of patients for each group. Surgical rescue was necessary in 4.6% and 7.8% of cases, and the overall mortality was 8.6% and 3.9% for elderly and advanced elderly patients, respectively. CONCLUSIONS MMA embolization can be used safely and effectively as an alternative or adjunctive minimally invasive treatment for NASHs in elderly and advanced elderly patients.
Background Olecranon fractures represent 10% of upper extremity fractures. There is a growing body of literature to support the use of plate fixation for displaced olecranon fractures. The purpose of ...this survey was to gauge Canadian surgeons’ practices and preferences for internal fixation methods for displaced olecranon fractures. Methods Using an online survey tool, we administered a cross-sectional survey to examine current practice for fixation of displaced olecranon fractures. Results We received 256 completed surveys for a response rate of 31% (95% confidence interval CI 30.5–37.5%). The preferred treatment was tension band wiring (78.5%, 95% CI 73–83%) for simple displaced olecranon fractures (Mayo IIA) and plating (81%, 95% CI 75.5–85%) for displaced comminuted olecranon fractures (Mayo IIB). Fracture morphology with a mean impact of 3.31 (95% CI 3.17–3.45) and comminution with a mean impact of 3.34 (95% CI 3.21–3.46) were the 2 factors influencing surgeons’ choice of fixation method the most. The major deterrent to using tension band wiring for displaced comminuted fractures (Mayo IIB) was increased stability obtained with other methods described by 75% (95% CI 69–80%) of respondents. The major deterrent for using plating constructs for simple displaced fractures (Mayo IIA) was better outcomes with other methods. Hardware prominence was the most commonly perceived complication using either method of fixation: 77% (95% CI 71.4–81.7%) and 76.2% (95% CI 70.6–81.0%) for tension band wiring and plating, respectively. Conclusion Divergence exists with current literature and surgeon preference for fixation of displaced olecranon fractures.
To assess acute gastrointestinal (GI) and genitourinary (GU) toxicities of intensity-modulated proton therapy (IMPT) targeting the prostate/seminal vesicles and pelvic lymph nodes for prostate ...cancer.
A prospective study (ClinicalTrials.gov: NCT02874014), evaluating moderately hypofractionated IMPT for high-risk or unfavorable intermediate-risk prostate cancer, accrued a target sample size of 56 patients. The prostate/seminal vesicles and pelvic lymph nodes were treated simultaneously with 6750 and 4500 centigray radiobiologic equivalent (cGyRBE), respectively, in 25 daily fractions. All received androgen-deprivation therapy. Acute GI and GU toxicities were prospectively assessed from 7 GI and 9 GU categories of the Common Terminology Criteria for Adverse Events (version 4), at baseline, weekly during radiotherapy, and 3-month after radiotherapy. Fisher exact tests were used for comparisons of categorical data.
Median age was 75 years. Median follow-up was 25 months. Fifty-five patients were available for acute toxicity assessment. Sixty-two percent and 2%, respectively, experienced acute grade 1 and 2 GI toxicity. Grade 2 GI toxicity was proctitis. Sixty-five percent and 35%, respectively, had acute grade 1 and 2 GU toxicity. The 3 most frequent grade 2 GU toxicities were urinary frequency, urgency, and obstructive symptoms. None had acute grade ≥ 3 GI or GU toxicity. The presence of baseline GI and GU symptoms was associated with a greater likelihood of experiencing acute GI and GU toxicity, respectively. Of 45 patients with baseline GU symptoms, 44% experienced acute grade 2 GU toxicity, compared with only 10% among 10 with no baseline GU symptoms (
= 0.07). Although acute grade 1 and 2 GI and GU toxicities were common during radiotherapy, most resolved at 3 months after radiotherapy.
A moderately hypofractionated IMPT targeting the prostate/seminal vesicles and regional pelvic lymph nodes was well tolerated with no acute grade ≥ 3 GI or GU toxicity. Patients with baseline GU symptoms had a higher rate of acute grade 2 GU toxicity.
Objectives This study sought to determine if an integrated healthcare system is selective and consistent in the use of angiography, as reflected by normal coronary rates. Background Rates of normal ...coronary arteries with elective coronary angiography vary considerably among U.S. community hospitals. This variation may in part reflect incentives in fee-for-service care. Methods Using national data from the Veterans Affairs (VA) Clinical Assessment Reporting and Tracking (CART) program representing all 76 VA cardiac catheterization laboratories, we evaluated all patients who underwent elective coronary angiography from October 2007 to September 2010. Normal coronary angiography was defined as <20% stenosis in all vessels. To assess hospital-level variation in normal coronary rates, we categorized hospitals by quartiles as defined by their proportion of normal coronaries. Results Overall, 4,829 of 22,538 patients (21.4%) had normal coronary angiography. Hospital proportions of normal coronaries varied markedly (median hospital proportion 20.5%; interquartile range: 15.1% to 25.3%; range: 5.5% to 48.5%). Categorized as hospital quartiles, the median proportion of normal coronaries in the lowest quartile was 10.8%, as compared with a median proportion of 19.1% in the second lowest quartile, 23.1% in the second highest quartile, and 30.3% in the highest quartile. Hospitals with lower rates of normal coronaries had higher rates of obstructive coronary disease (59.2% vs. 51.3% vs. 52.6% vs. 44.3%; p < 0.001) and subsequent revascularization (38.1% vs. 33.9% vs. 31.5% vs. 29.3%; p < 0.001). Conclusions Approximately 1 in 5 patients undergoing elective coronary angiography in the VA had normal coronaries. This rate is lower than prior published studies in other systems. However, the observed hospital-level variation in normal coronary rates suggests opportunities to improve patient selection for diagnostic coronary angiography.
Summary Background Angiogenesis is a valid target in the treatment of epithelial ovarian cancer. Trebananib inhibits the binding of angiopoietins 1 and 2 to the Tie2 receptor, and thereby inhibits ...angiogenesis. We aimed to assess whether the addition of trebananib to single-agent weekly paclitaxel in patients with recurrent epithelial ovarian cancer improved progression-free survival. Methods For this randomised, double-blind phase 3 study undertaken between Nov 10, 2010, and Nov 19, 2012, we enrolled women with recurrent epithelial ovarian cancer from 32 countries. Patient eligibility criteria included having been treated with three or fewer previous regimens, and a platinum-free interval of less than 12 months. We enrolled patients with a computerised interactive voice response system, and patients were randomly assigned using a permuted block method (block size of four) in a 1:1 ratio to receive weekly intravenous paclitaxel (80 mg/m2 ) plus either weekly masked intravenous placebo or trebananib (15 mg/kg). Patients were stratified on the basis of platinum-free interval (≥0 and ≤6 months vs >6 and ≤12 months), presence or absence of measurable disease, and region (North America, western Europe and Australia, or rest of world). The sponsor, investigators, site staff, and patients were masked to the treatment assignment. The primary endpoint was progression-free survival assessed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov , NCT01204749 , and is no longer accruing patients. Findings 919 patients were enrolled, of whom 461 were randomly assigned to the trebananib group and 458 to the placebo group. Median progression-free survival was significantly longer in the trebananib group than in the placebo group (7·2 months 5·8–7·4 vs 5·4 months 95% CI 4·3–5·5, respectively, hazard ratio 0·66, 95% CI 0·57–0·77, p<0·0001). Incidence of grade 3 or higher adverse events was similar between treatment groups (244 54% of 452 patients in the placebo group vs 258 56% of 461 patients in the trebananib group). Trebananib was associated with more adverse event-related treatment discontinuations than was placebo (77 17% patients vs 27 6%, respectively) and higher incidences of oedema (294 64% patients had any-grade oedema in the trebananib group vs 127 28% patients in the placebo group). Grade 3 or higher adverse events included ascites (34 8% in the placebo group vs 52 11% in the trebananib group), neutropenia (40 9% vs 26 6%), and abdominal pain (21 5% vs 22 5%). We recorded serious adverse events in 125 (28%) patients in the placebo group and 159 (34%) patients in the trebananib group. There was a difference of 2% or less in class-specific adverse events associated with anti-VEGF therapy (hypertension, proteinuria, wound-healing complications, thrombotic events, gastrointestinal perforations), except bleeding, which was more common in the placebo group than in the trebananib group (75 17% vs 46 10%). Interpretation Inhibition of angiopoietins 1 and 2 with trebananib provided a clinically meaningful prolongation in progression-free survival. This non-VEGF anti-angiogenesis option for women with recurrent epithelial ovarian cancer should be investigated in other settings and in combination with additional agents. Although oedema was increased, typical anti-VEGF associated adverse events were not prominent. Funding Amgen.
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