The Safety and Efficacy of Cyclosporine A in the Prevention of Vasospasm in Patients with Fisher Grade 3 Subarachnoid Hemorrhages: A Pilot Study

Recent advances in neuroradiology have made it possible to dilate human cerebral arteries that show vasospasm following aneurysmal subarachnoid hemorrhage (SAH), but the time window is short and the success rate for reversal of delayed ischemic neurological deficit (DIND) varies between 31% and 77%. In a canine model of vasospasm, transluminal balloon angioplasty (TBA) performed on Day 0 (the day of aneurysm rupture) has been shown to completely prevent the development of angiographically demonstrated narrowing by Day 7; this effect is better than any pharmacological treatment for vasospasm thus far described. The authors conducted a pilot trial to assess the safety and efficacy of TBA performed within 3 days post-SAH. Twelve patients with a very high probability of developing vasospasm (Fisher Grade 3) were included. Target vessels for prophylactic TBA were the internal carotid artery, A1 segment, M1 segment, and P1 segment bilaterally, the basilar artery, and the vertebral artery. No patient developed DIND or more than mild vasospasm, according to transcranial Doppler criteria. At 3 months, seven patients made a good recovery, two patients were moderately disabled, and three patients died; one patient died because of a vessel rupture during TBA and two older patients died of medical complications associated with an already poor clinical condition at admission. Compared with the results of large series reported in literature of patients with aneurysmal SAH, the results of this pilot study indicate an extremely low incidence of vasospasm and DIND after patients underwent prophylactic TBA. A larger, randomized study, however, is required to determine whether prophylactic TBA is efficacious enough to justify the risks.

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Magnesium Sulfate in the Management of Patients with Fisher Grade 3 Subarachnoid Hemorrhage: A Pilot Study

Neurosurgery ◽

10.1227/00006123-200009000-00014 ◽

2000 ◽

Vol 47 (3) ◽

pp. 602-607 ◽

Cited By ~ 4

Author(s):

Ronald Boet ◽

Edward Mee

Keyword(s):

Subarachnoid Hemorrhage ◽

Pilot Study ◽

Magnesium Sulfate ◽

Fisher Grade ◽

Grade 3

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The prophylactic use of transluminal balloon angioplasty in patients with Fisher Grade 3 subarachnoid hemorrhage: a pilot study

Journal of Neurosurgery ◽

10.3171/jns.1999.91.1.0051 ◽

1999 ◽

Vol 91 (1) ◽

pp. 51-58 ◽

Cited By ~ 77

Author(s):

J. Paul Muizelaar ◽

Marike Zwienenberg ◽

Nancy A. Rudisill ◽

Stephen T. Hecht

Keyword(s):

Subarachnoid Hemorrhage ◽

Pilot Study ◽

Balloon Angioplasty ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Pilot Trial ◽

Neurological Deficits ◽

Content Type ◽

Fisher Grade ◽

Grade 3 ◽

Fine Print

Object. Recent advances in neuroradiology have made it possible to dilate vasospastic human cerebral arteries after aneurysmal subarachnoid hemorrhage (SAH), but the time window is short and the success rate for reversal of delayed ischemic neurological deficits (DINDs) varies between 31% and 77%. In a dog model of vasospasm, transluminal balloon angioplasty (TBA) performed on Day 0 totally prevented the development of angiographically demonstrated narrowing on Day 7. Because the effect of preventive TBA in this animal model was better than any pharmacological treatment described previously for experimental vasospasm, the authors conducted a pilot trial in humans to assess the safety and efficacy of TBA performed within 3 days of SAH.Methods. The study group consisted of 13 patients with Fisher Grade 3 SAH who had a very high probability of developing vasospasm. In all patients, regardless of the site of the ruptured aneurysm, target vessels for prophylactic TBA were as follows: the internal carotid artery, A1 segment, M1 segment, and P1 segment bilaterally; the basilar artery; and one vertebral artery. Prophylactic TBA was considered satisfactory when it could be performed in at least two of the three parts of the intracranial circulation (right and/or left carotid system and/or vertebrobasilar system), and included the aneurysm-bearing part of the circulation. Of the 13 patients, none developed a DIND or more than mild vasospasm according to transcranial Doppler ultrasonography criteria. At 3 months posttreatment eight patients had made a good recovery, two were moderately disabled, and three had died; one patient died because of a vessel rupture during TBA and two elderly individuals died of medical complications associated with poor clinical condition on admission.Conclusions. Compared with large series of patients with aneurysmal SAH reported in the literature, the results of this pilot study indicate an extremely low incidence of vasospasm and DIND after treatment with prophylactic TBA. A larger randomized study is required to determine whether prophylactic TBA is efficacious enough to justify the risks, and which vessels need to be dilated prophylactically.

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Phase 2a Pilot Study to Explore Safety and Efficacy of NBMI Treatment in Patients With Beta Thalassemia Major, Requiring Iron Chelation

Case Medical Research ◽

10.31525/ct1-nct04092205 ◽

2019 ◽

Author(s):

Keyword(s):

Pilot Study ◽

Iron Chelation ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Safety And Efficacy ◽

Beta Thalassemia Major

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Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

Current Drug Safety ◽

10.2174/1574886313666181001120752 ◽

2019 ◽

Vol 14 (1) ◽

pp. 31-36

Author(s):

Raafat Abdel-Malek ◽

Kyrillus S. Shohdy ◽

Noha Abbas ◽

Mohamed Ismail ◽

Emad Hamada ◽

...

Keyword(s):

Pilot Study ◽

Adverse Events ◽

Urothelial Carcinoma ◽

Transitional Cell ◽

Chemotherapeutic Agents ◽

Serious Adverse Events ◽

Platinum Based Chemotherapy ◽

Number Of Patients ◽

Advanced Urothelial Carcinoma ◽

Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

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Carbon ion radiotherapy for prostate cancer with bladder invasion

BMC Urology ◽

10.1186/s12894-021-00871-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuhei Miyasaka ◽

Hidemasa Kawamura ◽

Hiro Sato ◽

Nobuteru Kubo ◽

Tatsuji Mizukami ◽

...

Keyword(s):

Prostate Cancer ◽

Locally Advanced ◽

Therapeutic Benefit ◽

Carbon Ion Radiotherapy ◽

Safety And Efficacy ◽

Carbon Ion ◽

Grade 3 ◽

Bladder Invasion

Abstract Background The optimal management of clinical T4 (cT4) prostate cancer (PC) is still uncertain. At our institution, carbon ion radiotherapy (CIRT) for nonmetastatic PC, including tumors invading the bladder, has been performed since 2010. Since carbon ion beams provide a sharp dose distribution with minimal penumbra and have biological advantages over photon radiotherapy, CIRT may provide a therapeutic benefit for PC with bladder invasion. Hence, we evaluated CIRT for PC with bladder invasion in terms of the safety and efficacy. Methods Between March 2010 and December 2016, a total of 1337 patients with nonmetastatic PC received CIRT at a total dose of 57.6 Gy (RBE) in 16 fractions over 4 weeks. Among them, seven patients who had locally advanced PC with bladder invasion were identified. Long-term androgen-deprivation therapy (ADT) was also administered to these patients. Adverse events were graded according to the Common Terminology Criteria for Adverse Event version 5.0. Results At the completion of our study, all the patients with cT4 PC were alive with a median follow-up period of 78 months. Grade 2 acute urinary disorders were observed in only one patient. Regarding late toxicities, only one patient developed grade 2 hematuria and urinary urgency. There was no grade 3 or worse toxicity, and gastrointestinal toxicity was not observed. Six (85.7%) patients had no recurrence or metastasis. One patient had biochemical and local failures 42 and 45 months after CIRT, respectively. However, the recurrent disease has been well controlled by salvage ADT. Conclusions Seven patients with locally advanced PC invading the bladder treated with CIRT were evaluated. Our findings seem to suggest positive safety and efficacy profiles for CIRT.

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Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial

BMJ Open ◽

10.1136/bmjopen-2020-048541 ◽

2021 ◽

Vol 11 (6) ◽

pp. e048541

Author(s):

Anna-Maria Hoffmann-Vold ◽

Håvard H Fretheim ◽

Vikas K Sarna ◽

Imon Barua ◽

Maylen N Carstens ◽

...

Keyword(s):

Systemic Sclerosis ◽

Pilot Study ◽

Phase Ii ◽

Intestinal Microbiome ◽

Induction Phase ◽

Inflammatory Disorder ◽

Faecal Microbiota ◽

Safety And Efficacy ◽

Faecal Microbiota Transplantation ◽

Patient Reported

IntroductionIn the multisystem inflammatory disorder systemic sclerosis (SSc), gastrointestinal tract (GIT) affliction is highly prevalent. There are no known disease modifying therapies and the negative impact is substantial. Aiming for a new therapeutic principle, and inspired by recent work showing associations between gut microbiota changes and GIT symptoms in SSc, we performed a pilot study on faecal microbiota transplantation (FMT) with the single-donor bacterial culture ‘Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)’. Motivated by positive pilot study signals, we designed the ReSScue trial as a phase II multicentre, placebo-controlled, randomised 20-week trial to evaluate safety and efficacy on lower GIT symptoms of FMT by ACHIM in SSc.Methods and analysesWe aim to include 70 SSc participants with moderate to severe lower GIT symptoms, defined by the validated patient-reported University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 2.0 questionnaire. The trial includes three parts. In part A1 (induction phase) lasting from week 0 to week 12, participants will be randomised 1:1 to repeat infusions of 30 mL ACHIM or placebo at week 0 and 2 by gastroduodenoscopy. In part A2, which is an 8-week subsequent maintenance phase, all study participants will receive 30 mL ACHIM at week 12 and followed until week 20 on continued blind. In part B, which will last until the last participant completes part A2, the participants will be followed through a maximum 16-week extended monitoring period, for longer-term data on safety and intervention effects. Primary endpoint is change from baseline to week 12 in UCLA GIT subscale scores of diarrhoea or bloating, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are safety measures and changes in UCLA GIT scores (total, diarrhoea and bloating).Ethics and disseminationThis protocol was approved by the Northern Norwegian Committee for Medical Ethics. Study findings will be published.Trial registration numberNCT04300426; Pre-results.Protocol versionV.3.1.

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