MON-LB110 A Phase 2 Evaluation of a Ready-To-Use Liquid Stable Continuous Subcutaneous Glucagon Infusion for the Treatment of Hypoglycemia Associated Autonomic Failure

Abstract OBJECTIVE:A novel, ready-to-use, liquid stable, continuous subcutaneous glucagon infusion (CSGI; Xeris Pharmaceuticals) was evaluated for the treatment of adults with type 1 diabetes (T1D) with documented Hypoglycemia Associated Autonomic Failure (HAAF). METHOD:This was a Phase 2 prospective, multi-center, randomized, placebo-controlled, double-blind, parallel trial in T1D adults with documented HAAF, defined as Gold Scale Score ≥4. Subjects were randomized in a 1:1:1 ratio to receive 4 weeks of continuous treatment (via Omnipod pump) with high rate CSGI (80mcg/hour), low rate CSGI, (20mcg/hour) or placebo (matched infusion rates for low and high rate CSGI). The primary endpoint evaluated at 4 weeks was the percent change of the epinephrine hormone response after 30 minutes of induced hypoglycemia. Epinephrine levels and hypoglycemia symptoms were recorded following a stepwise hypoglycemia clamp, and results compared between study treatment arms. Following the first four weeks, subjects continued for an additional 24 weeks to assess their epinephrine hormone response to hypoglycemia measured at 3 months post-treatment (16 weeks), and 6 months post-treatment (28 weeks). RESULTS:Forty-nine subjects were randomized to receive treatment with high rate CSGI (n=15), low rate CSGI (n=18), or matching placebo (n=16). At the end of study treatment, there were no statistically significant differences between the treatment arms for percent change of epinephrine hormone response during a stepwise hypoglycemia clamp (CSGI vs. placebo; p=0.160). As a result, long-term follow-up of the subjects was stopped early. The long-term follow-up data collected to date will be reported separately. The administration of low and high rate CSGI was associated with mild to moderate nausea (5.9%, 20%, respectively) and vomiting (11.8%, 13.3%, respectively) that was self-limited and required no additional intervention. In this 4-week assessment, CSGI was not associated with pain nor significant injection site reactions, and no SAEs related to CSGI were reported. CONCLUSION:In this proof-of-concept study, CSGI did not demonstrate statistically significant improvements in plasma epinephrine concentration when compared to placebo at 4 weeks. While there were positive epinephrine and improved hypoglycemia awareness responses observed in some subjects, the equivocal efficacy results observed may be explained by the unanticipated and incomplete elimination of hypoglycemia on CSGI therapy, and those on placebo therapy experienced hypoglycemia improvement. CSGI can be safely used with concomitant diabetes medications, and there were no SAEs related to CSGI. The 4-week administration of both low and high rate CSGI was safe and well tolerated.

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High-rate hepatitis and low-rate rejection induced late morbidity and mortality in long-term follow-up after liver transplantation

Transplantation Proceedings ◽

10.1016/s0041-1345(98)00447-3 ◽

1998 ◽

Vol 30 (5) ◽

pp. 1828-1829 ◽

Cited By ~ 3

Author(s):

L Caccamo ◽

G Rossi ◽

B Gridelli ◽

U Maggi ◽

P Reggiani ◽

...

Keyword(s):

Liver Transplantation ◽

Morbidity And Mortality ◽

High Rate ◽

Late Morbidity ◽

Long Term Follow Up ◽

Low Rate

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Endovascular Treatment of Anterior Circulation Aneurysms With the p64 Flow Modulation Device: Mid- and Long-Term Results in 617 Aneurysms From a Single Center

Operative Neurosurgery ◽

10.1093/ons/opaa425 ◽

2021 ◽

Author(s):

Marta Aguilar Pérez ◽

Elina Henkes ◽

Victoria Hellstern ◽

Carmen Serna Candel ◽

Christina Wendl ◽

...

Keyword(s):

Intracranial Aneurysms ◽

High Rate ◽

Long Term Results ◽

Effective Treatment Option ◽

Anterior Circulation ◽

Acute Hemorrhage ◽

Unruptured Aneurysms ◽

Long Term Follow Up

Abstract BACKGROUND Flow diverters have become an important tool in the treatment of intracranial aneurysms, especially when dealing with difficult-to-treat or complex aneurysms. The p64 is the only fully resheathable and mechanically detachable flow diverter available for clinical use. OBJECTIVE To evaluate the safety and effectiveness of p64 for the treatment of intracranial saccular unruptured aneurysms arising from the anterior circulation over a long-term follow-up period. METHODS We retrospectively reviewed our prospectively maintained database to identify all patients who underwent treatment for an intracranial saccular (unruptured or beyond the acute hemorrhage phase) aneurysm arising from the anterior circulation with ≥1 p64 between December 2011 and December 2019. Fusiform aneurysms and dissections were excluded. Aneurysms with prior or concomitant saccular treatment (eg, coiling and clipping) were included. Aneurysms with parent vessel implants other than p64 were excluded. Anatomic features, intraprocedural complications, clinical outcome, as well as clinical and angiographic follow-ups were all recorded. RESULTS In total, 530 patients (388 females; median age 55.9 yr) with 617 intracranial aneurysms met the inclusion criteria. The average number of devices used per aneurysm was 1.1 (range 1-3). Mean aneurysm dome size was 4.8 mm (range 1-27 mm). Treatment-related morbimortality was 2.4%. Early, mid-term, and long-term angiographic follow-up showed complete or near-complete aneurysm occlusion in 76.8%, 89.7%, and 94.5%, respectively. CONCLUSION Treatment of intracranial saccular unruptured aneurysms of the anterior circulation using p64 is a safe and effective treatment option with high rate of occlusion at long-term follow-up and low morbimortality.

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Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial

Journal of Hematology & Oncology ◽

10.1186/s13045-020-01004-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Robert J. Kreitman ◽

◽

Claire Dearden ◽

Pier Luigi Zinzani ◽

Julio Delgado ◽

...

Keyword(s):

Hairy Cell Leukemia ◽

Residual Disease ◽

Braf Inhibitor ◽

Nucleoside Analogs ◽

High Rate ◽

Hairy Cell ◽

Cell Leukemia ◽

Long Term Follow Up

Abstract Background Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy. Trial registration ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711

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A phase 2 study of sequential neoadjuvant chemotherapy with gemcitabine and doxorubicin followed by gemcitabine and cisplatin in patients with large or locally advanced operable breast cancer: results from long-term follow-up

Breast Cancer ◽

10.1007/s12282-012-0343-4 ◽

2012 ◽

Vol 20 (4) ◽

pp. 357-362 ◽

Cited By ~ 4

Author(s):

Pramod K. Julka ◽

Raju T. Chacko ◽

Shona Nag ◽

Rajinder Parshad ◽

Aravindan Nair ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Locally Advanced ◽

Operable Breast Cancer ◽

Phase 2 ◽

Phase 2 Study ◽

Long Term Follow Up ◽

Gemcitabine And Cisplatin

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Extramedullary Plasmacytoma of The Frontal Sinus: A Case Report

FACE ◽

10.1177/27325016211053640 ◽

2021 ◽

pp. 273250162110536

Author(s):

Joshua Harrison ◽

Samantha Marley ◽

Shawhin Shahriari ◽

Christian Bowers ◽

Anil Shetty

Keyword(s):

Frontal Sinus ◽

Surgical Excision ◽

Extramedullary Plasmacytoma ◽

High Rate ◽

Solitary Plasmacytoma ◽

Case Presentation ◽

Long Term Follow Up ◽

History Of

We report a rare case of an extramedullary plasmacytoma (EMP) in the frontal sinus with an indolent clinical presentation. Although a history of trauma was absent, the initial diagnosis was a mucocele, based on the radiological findings. Upon surgical excision, the patient was found to have an EMP. EMP, a form of solitary plasmacytoma, has a significantly high rate of conversion to multiple myeloma. This mandates long-term follow-up, even after successful radiotherapy and/or resection. While radiation therapy is generally considered a first line treatment for EMP, surgical intervention may provide optimal treatment in complicated cases. This case presentation highlights the prognosis of patients diagnosed with EMP.

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Nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (NSCLC): 4-year update from CheckMate 227.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9016 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9016-9016

Author(s):

Luis G. Paz-Ares ◽

Tudor-Eliade Ciuleanu ◽

Jong-Seok Lee ◽

Laszlo Urban ◽

Reyes Bernabe Caro ◽

...

Keyword(s):

Advanced Nsclc ◽

Performance Status ◽

Stage Iv ◽

Ecog Performance Status ◽

Programmed Death ◽

Long Term Follow Up ◽

To Receive ◽

Clinical Trial Information

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 < 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 < 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 < 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]

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Reduction and Association of the Scaphoid and Lunate: A Functional and Radiographical Outcome Study

Journal of Wrist Surgery ◽

10.1055/s-0038-1668154 ◽

2018 ◽

Vol 08 (01) ◽

pp. 037-042

Author(s):

William Aibinder ◽

Ali Izadpanah ◽

Bassem Elhassan

Keyword(s):

Range Of Motion ◽

Grip Strength ◽

High Rate ◽

Salvage Procedure ◽

Level Of Evidence ◽

Long Term Follow Up ◽

The Mean ◽

Ligament Disruption

Background Management of scapholunate (SL) ligament disruption is a challenging problem. The reduction and association of the scaphoid and lunate (RASL) procedure has been described with varying results. This study assessed the outcomes of the RASL procedure. Purpose The objective of this study was to assess the outcomes of patients undergoing the RASL procedure at our institution in regard to pain relief, range of motion, radiographic and functional outcomes, complications, and reoperations. Materials and Methods Twelve patients with symptomatic chronic SL instability underwent the RASL procedure. The mean age was 35 years. The mean time from injury to surgery was 40 weeks. The mean follow-up was 89 months. Outcomes included visual analog score for pain, wrist range of motion, grip strength, and Mayo Wrist Scores. Preoperative and postoperative radiographs were reviewed. Results Pain scores improved in 10 wrists. Range of motion and grip strength worsened. The average Mayo Wrist Score was 63.3. The mean SL diastasis and angle improved, but seven wrists developed progressive degenerative changes, with two requiring a salvage procedure. Symptomatic progressive screw lucency occurred in eight wrists requiring screw removal. Conclusion The RASL procedure can improve SL widening but has a high rate of early failure and reoperation. Following reoperation, long-term follow-up demonstrates reasonable long-term durability in some cases. Level of Evidence This is a Level IV, therapeutic case study.

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