Is intravitreal topotecan toxic to retinal function?

2020 ◽  
pp. bjophthalmol-2020-316588
Author(s):  
Jennifer Nadelmann ◽  
Jasmine H Francis ◽  
Scott E Brodie ◽  
Engjel Muca ◽  
David H Abramson
Keyword(s):  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Retinal Toxicity ◽  
Cancer Center ◽  
Ocular Toxicity ◽  
Significant Difference ◽  
Vitreous Seeds ◽  
Paired T Test

BackgroundIntravitreal injections of topotecan are used in the management of retinoblastoma with vitreous seeds. This study evaluated whether intravitreal topotecan was associated with retinal toxicity.MethodsRetrospective cohort study of patients with retinoblastoma who were treated with intravitreal topotecan at Memorial Sloan Kettering Cancer Center between December 2014 and May 2019. Electroretinogram (ERG) responses under anaesthesia were measured immediately before treatment with intravitreal topotecan and at the next visitor approximately one-month. Ocular toxicity was defined by a decrease in the ERG response at 30 Hz at follow-up.ResultsOcular toxicity was evaluated by ERG on 50 evaluable injections administered to 28 eyes. 22 (44.0%) injections were performed with concurrent intravitreal melphalan. The median time to ERG measurement following an injection was 27 days. By using a paired t-test, intravitreal topotecan combined with melphalan (n=22) at a dose of 25 μg or 30 μg was associated with a significant decrease in ERG amplitude at follow-up (p=0.046, 95% CI −20.4 μV to −0.2 μV). Among eyes that only received topotecan (n=28) at doses of 20 μg or 30 μg, there was not a significant difference in ERG amplitude measured (p=0.85, 95% CI −7.0 μV to 5.8 μV).ConclusionIntravitreal topotecan combined with intravitreal melphalan was associated with a decrease in ERG amplitude; there was not a significant decrease in ERG amplitude observed in patients who received topotecan alone. These findings suggest that intravitreal topotecan injections at doses of 20 μg or 30 μg are not associated with retinal toxicity in patients with retinoblastoma.

scholarly journals Evaluation of intravitreal topotecan dose levels, toxicity and efficacy for retinoblastoma vitreous seeds: a preclinical and clinical study

2021 ◽  
pp. bjophthalmol-2020-318529
Author(s):  
Carley M Bogan ◽  
Jessica V Kaczmarek ◽  
Janene M Pierce ◽  
Sheau-chiann Chen ◽  
Kelli L Boyd ◽  
...  
Keyword(s):  
Cohort Study ◽  
Clinical Study ◽  
Tumour Cell ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Rabbit Model ◽  
Retinal Toxicity ◽  
Apoptosis Induction ◽  
Dose Levels ◽  
Vitreous Seeds

BackgroundCurrent melphalan-based intravitreal regimens for retinoblastoma (RB) vitreous seeds cause retinal toxicity. We assessed the efficacy and toxicity of topotecan monotherapy compared with melphalan in our rabbit model and patient cohort.MethodsRabbit experiments: empiric pharmacokinetics were determined following topotecan injection. For topotecan (15 μg or 30 µg), melphalan (12.5 µg) or saline, toxicity was evaluated by serial electroretinography (ERG) and histopathology, and efficacy against vitreous seed xenografts was measured by tumour cell reduction and apoptosis induction. Patients: retrospective cohort study of 235 patients receiving 990 intravitreal injections of topotecan or melphalan.ResultsIntravitreal topotecan 30 µg (equals 60 µg in humans) achieved the IC90 across the rabbit vitreous. Three weekly topotecan injections (either 15 µg or 30 µg) caused no retinal toxicity in rabbits, whereas melphalan 12.5 µg (equals 25 µg in humans) reduced ERG amplitudes 42%–79%. Intravitreal topotecan 15 µg was equally effective to melphalan to treat WERI-Rb1 cell xenografts in rabbits (96% reduction for topotecan vs saline (p=0.004), 88% reduction for melphalan vs saline (p=0.004), topotecan vs melphalan, p=0.15). In our clinical study, patients received 881 monotherapy injections (48 topotecan, 833 melphalan). Patients receiving 20 µg or 30 µg topotecan demonstrated no significant ERG reductions; melphalan caused ERG reductions of 7.6 μV for every injection of 25 µg (p=0.03) or 30 µg (p<0.001). Most patients treated with intravitreal topotecan also received intravitreal melphalan at some point during their treatment course. Among those eyes treated exclusively with topotecan monotherapy, all eyes were salvaged.ConclusionsTaken together, these experiments suggest that intravitreal topotecan monotherapy for the treatment of RB vitreous seeds is non-toxic and effective.

scholarly journals Comparison of outcomes of ORIF versus bidirectional tractor and arthroscopically assisted CRIF in the treatment of lateral tibial plateau fractures: a retrospective cohort study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiangtian Deng ◽  
Hongzhi Hu ◽  
Yiran Zhang ◽  
Weijian Liu ◽  
Qingcheng Song ◽  
...  
Keyword(s):  
Cohort Study ◽  
Internal Fixation ◽  
Clinical Outcomes ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Tibial Plateau ◽  
Clinical Score ◽  
Lateral Tibial Plateau ◽  
Significant Difference

Abstract Background Lateral tibial plateau fractures (TPFs) are often treated with conventional open reduction and internal fixation (ORIF) through standard anterolateral sub-meniscal arthrotomy. There has been increasing support for “bidirectional rapid redactor” device-assisted closed reduction and internal fixation (CRIF) for treating TPFs. The aim of the present study is to compare the clinical and radiological outcomes between CRIF and ORIF procedures. Methods We performed a retrospective cohort study of 55 lateral TPF patients (Schatzker types I–III) who accepted surgical treatment at our trauma level 1 center between January 2016 and January 2018. They were divided into the CRIF group (32 patients) and the ORIF group (23 patients) based upon the different surgical protocols. The patients’ clinical outcome analysis was evaluated by using the Knee Society Score (KSS) and Rasmussen’s clinical score. For radiological assessment, changes in tibial plateau width (TPW), articular depression depth (ADD), medial proximal tibial angle (MPTA), and posterior tibial slope angle (PTSA) were evaluated using radiographs and computed tomography (CT) scan. Results The CRIF group had a mean follow-up of 28.9 months, and the ORIF group had a mean follow-up of 30.7 months (p>0.05). Furthermore, there was no statistically significant difference in terms of age, gender, injury mechanism, follow-up time, time interval from injury to surgery, and Schatzker classification in the two groups. With respect to the clinical outcomes including the KSS score and Rasmussen’s clinical score, there was also no significant difference (p>0.05). Nevertheless, the CRIF group had lower intra-operative blood loss, shorter hospitalization days, and better range of movement of the knee joint than the ORIF group (p<0.05). Furthermore, CRIF had better radiological results when compared to the ORIF group using Rasmussen’s radiological score (p<0.05), although no significant difference was observed in TPW, ADD, MPTA, and PTSA between the two groups (p>0.05). Conclusion The present study showed that CRIF could achieve comparable clinical outcomes and better radiological results for treating lateral TPFs as compared with conventional ORIF.

Does left atrial appendage morphology have any impact on the results of percutaneous closure?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Constantin ◽  
A Cinaud ◽  
F Brigadeau ◽  
A Lepillier ◽  
B Pierre ◽  
...  
Keyword(s):  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Left Atrial ◽  
Retrospective Cohort ◽  
Left Atrial Appendage ◽  
Cardiac Computed Tomography ◽  
Atrial Appendage ◽  
Significant Difference ◽  
The Impact

Abstract Introduction Transcatheter left atrial appendage (LAA) occlusion is an alternative treatment in patients with atrial fibrillation (AF), high CHADSVASC Score and a contra-indication to anticoagulants. This retrospective cohort study aims to evaluate the impact of LLA morphology on procedure outcomes. Methods Patients from eight French centers who underwent left atrial appendage occlusion from February 2012 to January 2017 were included in this retrospective cohort study. LLA morphology was described by preoperative cardiac computed tomography (CT). Clinical data and Transoesophageal echocardiography (TEE) or CT results were collected during follow-up. Results Among 469 included patients, LAA morphologies were described in 215 cases 45.8%), 150 patients (70%) were implanted with Watchman devices, 57 (26%) with Amplatzer devices and 8 procedures (4%) failed. LAA Morphology was Chicken Wing (34%), Windsock (45%), cauliflower (18%) and 3% had another morphology including Cactus. There was no difference in patient characteristics between the different morphology groups. Mean follow-up was 9.6±11 months, during which 190 patients underwent LAA imaging (TEE in 171 and CT in 19 patients). There was no significant difference in the failure rate (p=0.72), duration of the procedure (p=0.065), peri-device leak (p=0.83) device-related thrombus (p=0.96) and the occurrence of stroke (p=1) during follow-up. Conclusion LLA morphology did not influence complication occurrence after occlusion in this cohort. Funding Acknowledgement Type of funding source: None

Retrospective cohort study of 68 sacral giant cell tumours treated with nerve-sparing surgery and evaluation on therapeutic benefits of denosumab therapy

2020 ◽  
Vol 102-B (2) ◽  
pp. 177-185 ◽  
Author(s):  
Chiao Yee Lim ◽  
Xingyu Liu ◽  
Fangzhou He ◽  
Haijie Liang ◽  
Yi Yang ◽  
...  
Keyword(s):  
Cohort Study ◽  
Giant Cell ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Control Group ◽  
Nerve Sparing ◽  
Therapeutic Benefits ◽  
Significant Difference ◽  
Giant Cell Tumours

Aims To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs). Methods This is a retrospective cohort study of patients with GCT who presented between January 2011 and July 2017. Intralesional curettage was performed and patients treated from 2015 to 2017 also received denosumab therapy. The patients were divided into three groups: Cohort 1: control group (n = 36); cohort 2: adjuvant denosumab group (n = 9); and cohort 3: neo- and adjuvant-denosumab group (n = 17). Results There were 68 patients within the study period. Six patients were lost to follow-up. The mean follow-up was 47.7 months (SD 23.2). Preoperative denosumab was found to reduce intraoperative haemorrhage and was associated with shorter operating time for tumour volume > 200 cm3. A total of 17 patients (27.4%) developed local recurrence. The locoregional control rate was 77.8% (7/9) and 87.5% (14/16) respectively for cohorts 2 and 3, in comparison to 66.7% (24/36) of the control group. The recurrence-free survival (RFS) rate was significantly higher for adjuvant denosumab group versus those without adjuvant denosumab during the first two years: 100% vs 83.8% at one year and 95.0% vs 70.3% at two years. No significant difference was found for the three-year RFS rate. Conclusion Preoperative denosumab therapy was found to reduce intraoperative haemorrhage and was associated with shorter operating times. Adjuvant denosumab was useful to prevent early recurrence during the first two years after surgery. Cite this article: Bone Joint J 2020;102-B(2):177–185.

scholarly journals Fertility outcomes subsequent to medical and surgical treatment for ectopic pregnancy: A retrospective cohort study in Iran

2021 ◽  
pp. 881-888
Author(s):  
Zahra Asgari ◽  
Venus Chegini ◽  
Reihaneh Hosseini ◽  
Mina Mohajeri ◽  
Iman Ansari
Keyword(s):  
Cohort Study ◽  
Ectopic Pregnancy ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Medical Center ◽  
Clinical Status ◽  
Live Births ◽  
Study Results ◽  
Significant Difference

Background: Ectopic pregnancy (EP) and its treatment methods may affect subsequent fertility outcomes. Objective: To compare methotrexate (MTX), laparoscopic salpingostomy, and salpingectomy methods of EP treatment and their effects on fertility outcomes. Materials and Methods: This retrospective cohort study was performed on women receiving a definitive diagnosis of tubular EP from 2014 to 2017 at Arash Medical Center, Tehran, Iran. In total, 194 women were studied, of which 64 were treated with MTX, 52 underwent salpingostomy, and 78 underwent salpingectomy, depending on their clinical status. Basic information, obstetrics history, and major outcomes of the treatment after an 18-month follow-up, including recurrence of EP, miscarriage, and successful intrauterine pregnancy (IUP), were recorded and variables were compared among the three groups. Results: There was no significant difference in fertility outcomes among the three groups. Among the studied variables, predictors of successful IUP after EP treatment were multiparity (Hazard Ratio (HR): 1.37; 95%CI: 1.06-1.77), no history of miscarriage (HR: 2.37; 95%CI: 1.01-5.56), and a higher number of live births (HR: 1.54; 95%CI: 1.01- 2.37). On the other hand, predictors of EP recurrence included nulliparity (HR: 1.61; 95%CI: 1.02-2.53) and a lower number of live births (HR: 3.84; 95%CI: 1.43-10.98). The effect of other factors, including the utilized therapeutic modalities, was not statistically significant. Conclusion: The current study results demonstrated that after an 18-month follow-up, fertility outcomes, including recurrence of EP and successful IUP, were not significantly different among the subjects with EP treated with MTX, salpingostomy, or salpingectomy. Further studies with long-term follow-ups are recommended. Key words: Ectopic pregnancy, Fertility, Methotrexate, Salpingostomy, Salpingectomy.

scholarly journals Evaluation of management strategies in patients with coronary ectasia: a retrospective cohort study

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Sierra Gonzalez De Cossio ◽  
F Solis-Jimenez ◽  
J A Viana Rojas ◽  
M Villalobos Pedroza ◽  
E Terrazas Cervantes ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cohort Study ◽  
Coronary Artery ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Management Strategies ◽  
Coronary Ectasia ◽  
Significant Difference ◽  
One Year

Abstract Background/Introduction Since patients with coronary ectasia have an increased risk of developing myocardial infarction and cardiovascular death, these patients could benefit from a more intensive treatment. Unfortunately, the evidence regarding outcomes with different management strategies is limited, especially with direct oral anticoagulants (DOAC). Purpose To compare clinical outcomes in patients with coronary ectasia based on the selected/chosen treatment strategy. Methods We conducted a retrospective cohort study in patients diagnosed with coronary artery ectasia. They were divided into 3 different groups based on the treatment they received at discharge and we evaluated the main cardiovascular outcomes at one-year follow-up. Results Between 2016 and 2019, 7,579 angiographies were performed, in which 510 patients with coronary ectasia were found (prevalence of 6.72%). Of these patients, 43.9% (n=224) had the diagnosis of STEMI, 21% NSTEMI (n=107), 5.1% unstable angina (n=26), 18.6% chronic stable angina (n=95) and other 11.4% (n=58). The angiographic distribution of the lesions was as follows: left main coronary artery 25.1%, Left descending coronary artery 62.7%, circumflex artery 52.1%, right coronary artery 79.2%. It was possible to obtain the follow-up of 363 patients (71.2%) because 25 died during their hospitalization and data of 122 were not available at the time of analysis. Three groups were formed based on the treatment: (1) Dual Antiplatelet Therapy (DAPT) in 47% (n=174); (2) DAPT + Vitamin K Antagonist (VKA) in 8.5% (n=31); (3) DAPT + DOAC in 6.6% (n=24). The overall MACE rate at 1-year of follow-up was 6.6% (n=15): 11 patients in the DAPT group (6.3%), 1 patient in the DAPT + VKA group (3.2%), and 3 patients in the DAPT + DOAC group (12.5%). During this period, 3 patients died from cardiovascular causes, all of them in the DAPT group. Myocardial infarction occurred in 12 patients, 8 in the DAPT group (4.2%), 1 in the DAPT + VKA group (3.2%) and 3 in the DAPT + DOAC group (12.5%). Stroke occurred in 2 patients: 1 patient in the DAPT group (0.5%) and 1 patient in the DAPT + DOAC group, 4.1% None of these findings were statistically significant. One-year occurrence of bleeding events was also evaluated: 23 patients presented a bleeding event, 14 in the DAPT group (8%), 7 in the DAPT + VKA group (22.5%) and 2 in the DAPT + DOAC group (8.3%); p=0.010. Conclusion(s) Our findings suggest that there is no statistically significant difference in the incidence of thrombotic complications, when comparing the treatment options. Patients using the combination of DAPT+VKA have a higher incidence of bleeding. FUNDunding Acknowledgement Type of funding sources: None.

Nonunion Rates in Hind- and Midfoot Arthrodesis in Current, Ex-, and Nonsmokers

2020 ◽  
pp. 107110072097126
Author(s):  
Jack Allport ◽  
Jayasree Ramaskandhan ◽  
Malik S. Siddique
Keyword(s):  
Risk Factor ◽  
Cohort Study ◽  
Relative Risk ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Smoking Status ◽  
Time Frame ◽  
Modifiable Risk Factor ◽  
Level Of Evidence ◽  
Significant Difference

Background: Nonunion rates in hind or midfoot arthrodesis have been reported as high as 41%. The most notable and readily modifiable risk factor that has been identified is smoking. In 2018, 14.4% of the UK population were active smokers. We examined the effect of smoking status on union rates for a large cohort of patients undergoing hind- or midfoot arthrodesis. Methods: In total, 381 consecutive primary joint arthrodeses were identified from a single surgeon’s logbook (analysis performed on a per joint basis, with a triple fusion reported as 3 separate joints). Patients were divided based on self-reported smoking status. Primary outcome was clinical union. Delayed union, infection, and the need for ultrasound bone stimulation were secondary outcomes. Results: Smoking prevalence was 14.0%, and 32.2% were ex-smokers. Groups were comparable for sex, diabetes, and body mass index. Smokers were younger and had fewer comorbidities. Nonunion rates were higher in smokers (relative risk, 5.81; 95% CI, 2.54-13.29; P < .001) with no statistically significant difference between ex-smokers and nonsmokers. Smokers had higher rates of infection ( P = .05) and bone stimulator use ( P < .001). Among smokers, there was a trend toward slower union with heavier smoking ( P = .004). Conclusion: This large retrospective cohort study confirmed previous evidence that smoking has a considerable negative effect on union in arthrodesis. The 5.81 relative risk in a modifiable risk factor is extremely high. Arthrodesis surgery should be undertaken with extreme caution in smokers. Our study shows that after cessation of smoking, the risk returns to normal, but we were unable to quantify the time frame. Level of Evidence: Level III, retrospective cohort study.

Status and Determinants of Treatment Outcomes Among New Tuberculosis Patients in South Korea: A Retrospective Cohort Study

2021 ◽  
pp. 101053952110005
Author(s):  
Hyunjin Son ◽  
Jeongha Mok ◽  
Miyoung Lee ◽  
Wonseo Park ◽  
Seungjin Kim ◽  
...  
Keyword(s):  
Cohort Study ◽  
South Korea ◽  
Success Rate ◽  
Treatment Outcomes ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Health Care Facilities ◽  
Tuberculosis Patients ◽  
Lost To Follow Up

This is a retrospective cohort study using notification data in South Korea. We evaluated the nationwide status, regional differences, and the determinants of treatment outcomes among tuberculosis patients. Treatment success rate improved from 77.0% in 2012 to 86.0% in 2015. The lost to follow-up rate was higher among older people, males, and foreign nationals. Health care facilities designated for the Public-Private Mix (PPM) project showed higher success rate and lower rate of lost to follow-up. Moreover, municipalities with low regional deprivation index had higher PPM project coverage. Since there is a large regional difference in the coverage of the PPM project, an additional community-based support program should be implemented, especially for tuberculosis patients residing in region with low PPM project coverage.

scholarly journals 387. Markers for Mortality in COVID-19 Patients with Atrial Fibrillation or Flutter

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S262-S262
Author(s):  
Kok Hoe Chan ◽  
Bhavik Patel ◽  
Iyad Farouji ◽  
Addi Suleiman ◽  
Jihad Slim
Keyword(s):  
Atrial Fibrillation ◽  
Logistic Regression ◽  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Prognostic Markers ◽  
Univariate Analysis ◽  
Laboratory Data ◽  
Significant Difference ◽  
New Onset

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection can lead to many different cardiovascular complications, we were interested in studying prognostic markers in patients with atrial fibrillation/flutter (A. Fib/Flutter). Methods A retrospective cohort study of patients with confirmed COVID-19 and either with existing or new onset A. Fib/Flutter who were admitted to our hospital between March 15 and May 20, 2020. Demographic, outcome and laboratory data were extracted from the electronic medical record and compared between survivors and non-survivors. Univariate and multivariate logistic regression were employed to identify the prognostic markers associated with mortality in patients with A. Fib/Flutter Results The total number of confirmed COVID-19 patients during the study period was 350; 37 of them had existing or new onset A. Fib/Flutter. Twenty one (57%) expired, and 16 (43%) were discharged alive. The median age was 72 years old, ranged from 19 to 100 years old. Comorbidities were present in 33 (89%) patients, with hypertension (82%) being the most common, followed by diabetes (46%) and coronary artery disease (30%). New onset of atrial fibrillation was identified in 23 patients (70%), of whom 13 (57%) expired; 29 patients (78%) presented with atrial fibrillation with rapid ventricular response, and 2 patients (5%) with atrial flutter. Mechanical ventilation was required for 8 patients, of whom 6 expired. In univariate analysis, we found a significant difference in baseline ferritin (p=0.04), LDH (p=0.02), neutrophil-lymphocyte ratio (NLR) (p=0.05), neutrophil-monocyte ratio (NMR) (p=0.03) and platelet (p=0.015) between survivors and non-survivors. With multivariable logistic regression analysis, the only value that had an odds of survival was a low NLR (odds ratio 0.74; 95% confidence interval 0.53–0.93). Conclusion This retrospective cohort study of hospitalized patients with COVID-19 demonstrated an association of increase NLR as risk factors for death in COVID-19 patients with A. Fib/Flutter. A high NLR has been associated with increased incidence, severity and risk for stroke in atrial fibrillation patients but to our knowledge, we are first to demonstrate the utilization in mortality predictions in COVID-19 patients with A. Fib/Flutter. Disclosures Jihad Slim, MD, Abbvie (Speaker’s Bureau)Gilead (Speaker’s Bureau)Jansen (Speaker’s Bureau)Merck (Speaker’s Bureau)ViiV (Speaker’s Bureau)

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