Intermittent Arm Research Articles

The Case for Intermittent Carbapenem Dosing in Stable Haemodialysis Patients.

Purpose: Antimicrobial resistant infections are common in patients on haemodialysis, often needing long courses of carbapenems. This results in a longer hospital stay and risk of iatrogenic complications. However, carbapenems can be given intermittently to allow for earlier discharge. We aim to describe the clinical outcomes of intermittent versus daily meropenem in stable, intermittently haemodialysed patients. Methods: In total, 103 records were examined retrospectively. Data collected include demographics, clinical interventions and outcomes such as hospital length of stay (LOS), 30-day readmission rates and adverse events. Findings: Mean age 61.6 ± 14.2 years, 57.3% male. Most common bacteria cultured were Klebsiella pneumoniae (16.5%). The most common indication was pneumonia (27.2%). Mean duration of therapy on meropenem was 12.4 ± 14.4 days; eight patients needed more than 30 days of meropenem. In total, 55.3% did not have intervention for source control; 86.4% received daily dosing of meropenem; 7.8% patients received intermittent dosing of meropenem only, and 5.8 patients received both types of dosing regimens. LOS of the index admission was shorter for the intermittent arm (15.5 ± 7.6 days versus daily: 30.2 ± 24.5 days), though 30-day readmission was higher (50% versus daily: 38.2%). Implications: We recommend further rigorous randomised controlled trials to investigate the clinical utility of intermittent meropenem dosing in patients on stable haemodialysis.

Abstract CT013: SWOG S1320: Improved progression-free survival with continuous compared to intermittent dosing with dabrafenib and trametinib in patients with BRAF mutated melanoma

Abstract Background: BRAF and MEK inhibitors yield objective responses in the majority of BRAFV600E/K mutant melanoma patients, but acquired resistance limits response durations. Preclinical data suggests that intermittent dosing of these agents may delay acquired resistance by deselecting tumor cells that grow optimally in the presence of these agents. S1320 is a randomized phase 2 clinical trial designed to determine whether intermittent versus continuous dosing of dabrafenib and trametinib improves progression-free survival (PFS) in patients with advanced BRAFV600E/K melanoma. Methods: All patients received continuous dabrafenib and trametinib for 8-weeks after which non-progressing patients were randomized to receive either continuous treatment or intermittent dosing of both drugs on a 3-week-off, 5-week-on schedule. Unscheduled treatment interruptions of both drugs for > 14 days were not permitted. Responses were assessed using RECIST v1.1 at 8-week intervals scheduled to coincide with on-treatment periods for patients on the intermittent dosing arm. Adverse events were assessed using CTCAE v4 monthly. The design assumed exponential PFS with a median of 9.4 months using continuous dosing, 206 eligible patients and 156 PFS events. It had 90% power with a two-sided α = 0.2 to detect a change to a median with an a priori hypothesis that intermittent dosing would improve the median PFS to 14.1 months using a Cox model stratified by the randomization stratification factors. Results: 242 patients were treated and 206 patients without disease progression after 8 weeks were randomized, 105 to continuous and 101 to intermittent treatment. 70% of patients had not previously received immune checkpoint inhibitors. There were no significant differences between groups in terms of baseline patient characteristics. The median PFS was statistically significantly longer, 9.0 months from randomization, with continuous dosing vs. 5.5 months from randomization with intermittent dosing (p = 0.064). There was no difference in overall survival between groups (median OS = 29.2 months in both arms p = 0.93) at a median follow up of 2 years. 77% of patient treated continuously discontinued treatment due to disease progression vs. 84% treated intermittently (p = 0.34). Conclusions: Continuous dosing with the BRAF and MEK inhibitors dabrafenib and trametinib yields superior PFS compared with intermittent dosing. Support: NIH/NCI grants CA180888, CA180819, CA180820 Citation Format: Alain Algazi, Megan Othus, Adil Daud, Roger Lo, Janice Mehnert, Thach-Giao Truong, Robert Conry, Kari Kendra, Gary Doolittle, Joseph I. Clark, Michael Messino, Dennis F. Moore, Christopher Lao, Bryan A. Faller, Rangaswamy Govindarajan, Amy Harker-Murray, Luke Dreisbach, James Moon, Kenneth Grossman, Antoni Ribas. SWOG S1320: Improved progression-free survival with continuous compared to intermittent dosing with dabrafenib and trametinib in patients with BRAF mutated melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT013.

The Use of Upper-Body Intermittent Sequential Pneumatic Compression Arm Sleeves on Recovery From Exercise in Wheelchair Athletes.

The aim of the current study was to investigate the efficacy of an upper-body intermittent sequential pneumatic compression device on recovery after wheelchair team sport activity. Eleven well-trained wheelchair basketball and rugby athletes (male, 8; female, 3; mean ± SD age = 33 ± 10 yrs) performed a series of performance measures pre-exercise, postexercise, and postrecovery (grip strength, pressure-to-pain threshold, medicine ball throw, wheelchair sprints, repeated sprints). Subjective muscle soreness and fatigue measurements were taken at the same time points as performance tests, with an additional 24-hr postrecovery measure. Participants completed two recovery trials, separated by 1 wk, of either passive recovery (control) or 20 mins of wearing recovery arm sleeves (intermittent sequential pneumatic compression) applied to both arms. No statistically significant differences were found between trials for any of the performance or perceptual measures (P > 0.05). However, effect size analysis revealed a moderate decrease (d = -0.67) from postexercise to postrecovery for muscle fatigue in favor of intermittent sequential pneumatic compression. A large decrease (d = -0.96) in muscle soreness was also found after exercise to 24 hrs after recovery in favor of intermittent sequential pneumatic compression over control. Intermittent sequential pneumatic compression may provide some benefit for perceptual recovery measures immediately after and 24 hrs after a high-intensity wheelchair activity with negligible effects on performance recovery.

Investigating the Use of an Intermittent Sequential Pneumatic Compression Arm Sleeve for Recovery After Upper-Body Exercise

Cranston, AW and Driller, MW. Investigating the use of an intermittent sequential pneumatic compression arm sleeve for recovery after upper-body exercise. J Strength Cond Res 36(6): 1548-1553, 2022-The current study aimed to investigate the efficacy of an intermittent sequential pneumatic compression (ISPC) device placed on the arm after a fatiguing upper-body exercise circuit. Fifty resistance-trained athletes (37 males/13 females, mean ± SD; age = 27 ± 4 years) performed 3 physical performance tests (grip strength dynamometer, single-arm medicine ball throw, and preacher bench bicep curls to failure) before and after exercise, following a 30-minute recovery period. During the recovery period, subjects were randomly assigned an experimental arm, which was placed in the ISPC device, and a control arm (no device). Subjects completed a perceptual muscle soreness rating through palpation of 4 muscle groups in the upper body at the same time points and also 24 hours after recovery. There was a statistically significant interaction between conditions for the single-arm medicine ball throw (p < 0.01) in favor of the ISPC after the recovery period; however, the effect size was deemed trivial. There was a small but not statistically significant effect (d = 0.22, p > 0.05) for the bicep curls in favor of the ISPC and no significant difference for the grip strength (d = 0.09, p > 0.05). The perceptual muscle soreness scales resulted in significant differences between conditions immediately after and 24 hours after exercise across all muscle groups (p < 0.05), all in favor of the ISPC condition. This study supports the use of an upper-body ISPC device to reduce perceived muscle soreness for up to 24 hours after exercise, with negligible effects on physical performance when compared with a control trial.

Physiological Responses To Acute Arm Cranking With Blood Flow Restriction

Aerobic exercise with blood flow restriction (BFR) is emerging as an effective method to improve both aerobic capacity and muscular function. Using an inflatable cuff, blood flow is usually restricted during walking and cycling. The extent to which BFR can be applied during upper-body aerobic exercise such as arm cranking is not well documented. Arm cranking with BFR might offer an exercise option for clinical populations that need to exercise upper-body muscles (e.g., wheelchair users, individuals with shoulder injuries). PURPOSE: To evaluate physiological and perceptual responses to acute submaximal arm cranking with BFR. METHODS: Five active adults (age: 23±3yrs, arm cranking VO2peak: 33±8ml/kg/min) performed 4 intermittent arm cranking protocols (6x2 min, 1min recovery): 1) low-load arm cranking (LL, 40% VO2peak), 2) low-load arm cranking with BFR (BFR, 40% VO2peak), and 3) high-load arm cranking (HL, 80% VO2peak). For BFR, blood flow was restricted using 5cm cuffs inflated to 70% of limb occlusion pressure as identified using Doppler ultrasound. Cardiorespiratory and perceptual responses (VO2, HR, perceived effort) and tissue perfusion (tissue saturation, deoxyhemoglobin concentrations) were measured using a metabolic cart and near-infrared spectroscopy, respectively. RESULTS: Oxygen consumption during BFR (1.15±0.32ml/kg/min) did not differ from LL (1.04±0.26ml/kg/min, P=0.31) and was less than HL (2.28±0.60ml/kg/min, P<0.01). Compared to LL (104±6b/min), heart rate during BFR increased (115±13b/min, P=0.04) but was less than HL (166±19b/min, P<0.01). BFR required greater perceived effort in the arms (12±3) compared to LL (9±2, P=0.03) but less effort than HL (16±2, P=0.01). In general, BFR decreased tissue saturation and increased deoxyhemoglobin concentrations compared to arm cranking without BFR (all P<0.05). CONCLUSION: These results suggest that arm cranking with BFR has potential to increase metabolic stress without excessive cardiorespiratory strain. This exercise mode may provide a useful alternative to HL for populations that need to exercise upper-body muscles for rehabilitation. These findings provide guidance for future acute and chronic studies examining the feasibility and efficacy of arm cranking with BFR.

MOMENTUM: A Phase I Trial Investigating 2 Schedules of Capecitabine With Aflibercept in Patients With Gastrointestinal and Breast Cancer

BackgroundAlthough data from preclinical and clinical studies provide a strong rationale for combining capecitabine with anti-angiogenic agents, clinical development of this fluoropyrimidine in combination with aflibercept has lagged behind other treatments. We conducted a nonrandomized, noncomparative, 2-arm, phase I trial to address this unmet need. Patients and MethodsPatients with chemorefractory gastrointestinal and breast cancer were sequentially recruited into a continuous (Arm A, starting dose 1100 mg/m2/day) or intermittent (Arm B, 2 weeks on/1 week off, starting dose 1700 mg/m2/day) capecitabine dosing arm. Aflibercept was administered at a flat dose of 6 mg/kg every 3 weeks in both arms. A classical 3 + 3, dose-escalation design was used. The primary objective was to establish the maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended dose for phase II trials. ResultsThirty-eight eligible patients were recruited of whom 33 were assessable for DLTs (15 in arm A and 18 in arm B). Fourteen had colorectal cancer, 8 gastric cancer, and 11 breast cancer. DLTs included grade 2 hand-foot syndrome, grade 2 anorexia considered unacceptable by the patient, and grade 3 hypertension. The recommended dose for phase II trials for capecitabine was established at 1300 mg/m2/day in Arm A and 2500 mg/m2/day in Arm B with treatment-related grade ≥ 3 adverse events occurring in 47% and 50% of patients, respectively. Among 26 assessable patients, the objective response rate was 15.4% in Arm A and 7.7% in Arm B. ConclusionCombining capecitabine with aflibercept is feasible and associated with a manageable safety profile and some anti-tumor activity in patients with chemorefractory gastrointestinal and breast cancer.

Randomized phase II trial of CAPOX with continuous versus intermittent use of oxaliplatin as an adjuvant chemotherapy after curative resection of stage II/III colon cancer (CCOG-1302 study).

95 Background: The aim of this study was to evaluate the efficacy and safety of CAPOX with intermittent use of oxaliplatin compared to continuous use of oxaliplatin as an adjuvant setting for colon cancer. Methods: Patients with curative resection of stage II or III colon cancer were randomly assigned to receive either CAPOX with continuous use of oxaliplatin (continuous arm: 8 cycles of CAPOX) or CAPOX with intermittent use of oxaliplatin (intermittent arm: 2 cycles of CAPOX→4 cycles of capecitabine→2 cycles of CAPOX). The primary endpoints were frequency of disease-free survival (DFS) rate at 3-year after surgery and peripheral sensory neuropathy (PSN) at 1-year after surgery. The secondary end points included DFS, overall survival (OS), compliance and safety. Results: A total of 200 patients were enrolled. The intent-to-treat and safety population comprised 100 and 99 patients in the continuous arm, and 100 and 98 patients in the intermittent arm, respectively. After a median follow-up period of 39 months, disease recurrence and death occurred in 37 patients (19%) and 8 patients (4%) in the ITT population, respectively. The 3-year DFS was 78% (95% CI, 70-87%) in the continuous arm and 82% (95% CI, 74-90%) in the intermittent arm (HR, 0.80; 95% CI, 0.42-1.52; p = 0.49). In the patients with stage III disease, the 3-year DFS was 76% (95% CI, 66-86%)in the continuous arm and 80% (95% CI, 71-88) in the intermittent arm(HR, 0.75; 95% CI, 0.38-1.51; p = 0.43). The frequencies of PSF at 1-year after surgery were 58% (95% CI, 48-68%) in the continuous arm and 19% (95% CI, 11-26%) in the intermittent arm (p &lt; 0.01), and those at 3-year after surgery were 37% (95% CI, 27-47%) and 9% (3-15%), respectively (p &lt; 0.01). Conclusions: CAPOX with planned intermittent use of oxaliplatin could be equally effective as an adjuvant setting for colon cancer, and substantially reduce long-term PSN and potential improve patient quality of life. Clinical trial information: UMIN 000012535.

Intermittent gastric feeds lower insulin requirements without worsening dysglycemia: A pilot randomized crossover trial.

Introduction:We hypothesized that critically ill medical patients would require less insulin when fed intermittently.Methods:First, 26 patients were randomized to receive intermittent or continuous gastric feeds. Once at goal nutrition, data were collected for the first 4-hr data collection period. Next, the enteral feed type was switched, goal nutrition was repeated, and a second 4-h data collection period was completed. The primary endpoint was the total amount of insulin infused; secondary endpoints were glucose concentration mean, maximum, minimum, and standard deviation, as well as episodes of hypoglycemia.Results:Sixteen of the 26 patients successfully completed the protocol. One patient experienced a large, rapid, and sustained decline in insulin requirement from liver failure, creating a bias of lesser insulin in the intermittent arm; this patient was removed from the analysis. For the remaining 15 patients, the average total amount of insulin infused was 1.4 U/patient/h less following intermittent feeds: P =0.027, 95% confidence interval (0.02, 11.17), and effect size 0.6. Secondary endpoints were statistically similar.Conclusions:Critically ill medical patients who require an insulin infusion have a reduced insulin requirement when fed intermittently, whereas dysglycemia metrics are not adversely affected. A larger clinical study is required to confirm these findings.

480 Successful anticoagulation treatment of an ascending aortic thrombus associated with myocardial infarction and systemic embolism

Abstract Background The ascending aorta is an uncommon site for non-infective mural thrombus. The detection of such a thrombus is of particular importance, given the risk of systemic and coronary embolisation. We present a case of a 60-year-old female with an ascending aortic thrombus complicated by non-ST-elevation myocardial infarction (NSTEMI), and associated systemic embolism in the form of renal and splenic infarcts. Case Report A 60-year-old female was admitted to a local secondary hospital with a 4-day history of crampy abdominal pain and intermittent bilateral arm pain associated with nausea and vomiting. Past medical history included known hypertrophic cardiomyopathy, gastroesophageal reflux disease, carpal tunnel syndrome, hepatic steatosis, but no known thrombophilia or coronary artery disease. Computer tomography (CT) scan of the abdomen revealed subacute infarction of the right kidney and spleen in keeping with a thrombo-embolic event. A CT pulmonary angiogram revealed a small pulmonary embolus in the right lower lobe. Troponin I level was elevated at 11 mg/L (normal &amp;lt;0.04 mg/L). She was treated with aspirin, clopidogrel and therapeutic enoxaparin for a NSTEMI, and transferred to a metropolitan tertiary centre for ongoing investigation. A transthoracic echocardiogram performed showed known hypertrophic cardiomyopathy, but negative for intracardiac shunting via bubble study. Coronary angiography revealed an acutely occluded distal left anterior descending (LAD) artery with no collaterals, and mild irregularities in all other coronary arteries. A transoesophageal echocardiogram performed to exclude any intracardiac sources of emboli showed a pedunculated and mobile non-calcific mass measuring 1.0cm X 0.5cm in the posterior aspect of the ascending aorta, associated with atheroma in the aortic arch. A laboratory workup for antiphospholipid syndrome, antithrombin III, protein S and protein C deficiency were negative. After discussion with the multidisciplinary Heart team, the consensus was that the aortic mass was likely thrombus formation relating to erosion of aortic atheroma. It was hypothesised that this may have resulted in distal embolisation to the left kidney and spleen, and possibly also caused embolisation to the LAD artery, although the cause of the pulmonary embolism was still unknown. The patient was then discharged on rivaroxaban and aspirin. A repeat transoesophageal echocardiogram was performed 4 months after discharge to assess the ascending aortic mass. It showed complete resolution of the mass in the ascending aorta, with no change in any other cardiac structures. Discussion Although thrombus formation is uncommon in the ascending aorta, certain conditions, such as pregnancy and thrombophilia increase its risk. Several case reports of ascending aortic thrombus were found in the literature, but this will be the first to report complete resolution with treatment using a direct oral anticoagulant. Abstract 480 Figure. Ascending Aortic Thrombus + Resolution

The influence on quality of life of intermittent scheduling in first- and second-line chemotherapy of patients with HER2-negative advanced breast cancer

BackgroundThe Stop&Go study randomized patients with advanced breast cancer to intermittent (two times four) or continuous (eight subsequent cycles) first- and second-line chemotherapy.MethodsQoL was measured with RAND-36 questionnaires every 12 weeks. The primary objective was to estimate differences in changes from baseline between intermittent and continuous treatment. An effect size of 0.5 SD (5 points) was considered clinically meaningful.ResultsA total of 398 patients were included with a median follow-up of 11.4 months (IQR 5.6–22.2). Mean physical QoL baseline scores were 38.0 resp. 38.2, and mental scores 45.0 resp. 42.4 for intermittent and continuous treatment. Physical QoL declined linearly in the intermittent arm causing a clinically meaningful difference of 5.40 points at 24 months (p < 0.001), while scores in the continuous arm stabilized after a small decline of ± 3.4 points at 12 months. Conversely, mental QoL was fairly stable and even improved with 1.58 (p = 0.005) and 2.48 points (p < 0.001) at 12 months for intermittent and continuous treatment, respectively. When comparing arms for both components in changes from baseline, the maximum differences were 2.46 (p = 0.101) and 1.95 points (p = 0.182) for physical and mental scores, both measured at 30 months and in favor of continuous treatment.ConclusionIntermittent first- and second-line chemotherapy in patients with HER2-negative advanced breast cancer showed a trend for worse impact on QoL compared to continuous chemotherapy, with neither significant nor meaningful differences in course. We recommend prescribing chemotherapy continuously until progressive disease or unacceptable toxicity.Trial registration EudraCT 2010-021519-18; BOOG 2010-02

Continuous versus intermittent infusion of cefotaxime in critically ill patients: a randomized controlled trial comparing plasma concentrations.

In critical care patients, reaching optimal β-lactam concentrations poses challenges, as infections are caused more often by microorganisms associated with higher MICs, and critically ill patients typically have an unpredictable pharmacokinetic/pharmacodynamic profile. Conventional intermittent dosing frequently yields inadequate drug concentrations, while continuous dosing might result in better target attainment. Few studies address cefotaxime concentrations in this population. To assess total and unbound serum levels of cefotaxime and an active metabolite, desacetylcefotaxime, in critically ill patients treated with either continuously or intermittently dosed cefotaxime. Adult critical care patients with indication for treatment with cefotaxime were randomized to treatment with either intermittent dosing (1 g every 6 h) or continuous dosing (4 g/24 h, after a loading dose of 1 g). We defined a preset target of reaching and maintaining a total cefotaxime concentration of 4 mg/L from 1 h after start of treatment. CCMO trial registration number NL50809.042.14, Clinicaltrials.gov NCT02560207. Twenty-nine and 30 patients, respectively, were included in the continuous dosing group and the intermittent dosing group. A total of 642 samples were available for analysis. In the continuous dosing arm, 89.3% met our preset target, compared with 50% in the intermittent dosing arm. Patients not reaching this target had a significantly higher creatinine clearance on the day of admission. These results support the application of a continuous dosing strategy of β-lactams in critical care patients and the practice of therapeutic drug monitoring in a subset of patients with higher renal clearance and need for prolonged treatment for further optimization, where using total cefotaxime concentrations should suffice.

LBA58 - BAROCCO: A randomized phase II study of weekly paclitaxel vs cediranib-olaparib combination given with continuous or intermittent schedule in patients with recurrent platinum resistant ovarian cancer (PROC)

BackgroundHypoxia induced by antiangiogenic agents could cause a functional impairment of homologous recombination, thus sensitizing wild-type (wt) BRCA tumor cells to PARP inhibition. In a phase II study the combination of cediranib-olaparib increased progression free survival (PFS) in women with recurrent platinum sensitive OC with respect to olaparib. Methods123 patients were allocated in a 1:1:1 ratio to receive: 80mg/m2 weekly paclitaxel up to 24 weeks (control), olaparib 600mg tablet (300mg twice daily) together with 20mg cediranib daily (continuous schedule) or 20mg cediranib given 5 days/week (intermittent schedule) until progression. PFS comparison between experimental schedules and the control arm (alpha one-sided 5%; power 80% to detect a HR of 0.5) was the primary objective. ResultsMedian platinum-free interval was 1.8 mos, 59% of patients were pretreated with >3 chemotherapy lines. Median PFS for paclitaxel, the continuous, and the intermittent schedules were 3.1, 5.7, and 3.8 mos. Estimated HR for PFS in continuous arm vs control was 0.76 (90% CI: 0.49-1.17), p=0.28 by log-rank test. HR for PFS in intermittent arm vs. control was 1.08 (90% CI: 0.71-1.64), p=0.76 by log-rank test. In the subgroup gBRCA wt (n=109) the median PFS for paclitaxel, the continuous, and the intermittent schedules were 2.1, 5.8 and 3.8 mos and HR for PFS in continuous arm vs control was 0.63 (95% CI: 0.36 to 1.10; p=0.10). The toxicity profile of the study arms was as expected and similar between experimental arms. 11%, 18%, and 7% in control, continuous and intermittent arm discontinued treatment for adverse events. Five serious adverse drug reactions occurred and two of these were fatal: one in the control and one in the continuous arm. ConclusionsThe combination of cediranib and olaparib is effective in heavily pretreated PROC patients with the advantage of an oral administration and good tolerability. The continuous schedule of cediranib-olaparib showed a promising trend towards improved PFS in comparison with weekly paclitaxel particularly in the BRCA wt population. Clinical trial identificationIRFMN-OVA-7289, EudraCT: 2016-003964-38, NCT03314740. Legal entity responsible for the studyIstituto di Ricerche Farmacologiche Mario Negri IRCCS. FundingAstraZeneca. DisclosureN. Colombo: Honoraria (self), Advisory / Consultancy: Roche/Genentech; Honoraria (self), Advisory / Consultancy: PharmaMar; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: BioCad; Advisory / Consultancy: Takeda. G. Tognon: Advisory / Consultancy: Amgen; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony: Tesaro. M. Ratti: Travel / Accommodation / Expenses: Tesaro Bio. All other authors have declared no conflicts of interest.

CATASTROPHIC AIRWAY COMPLICATIONS STATUS POST ANTERIOR CERVICAL DISCECTOMY AND FUSION

SESSION TITLE: Tuesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Anterior cervical discectomy and fusion is a commonly performed spine surgery and considered a relatively safe procedure. It usually carries a small risk of postoperative complications, however, airway compromise after cervical spine surgery can be catastrophic and one that all providers should be aware of. Here we present a case of catastrophic airway complication status post anterior cervical discectomy and fusion. CASE PRESENTATION: We present a 75 year-old female with long history of C2 fracture with anterior displacement secondary to fall with intermittent left arm numbness and weakness who presented for a scheduled C3/4/5 Anterior Cervical Discectomy and Fusion. Patient had a prolonged surgical fixation resulting in prolonged duration of time in the prone position. The patient had significant facial and upper airway swelling and was therefore not extubated postop due to the concerns of the above mentioned swelling. The following morning, the swelling improved and the patient was extubated with no complications. Postop day 2, the patient developed stridor which did not respond to dexamethasone or racemic epinephrine. The neck swelling quickly worsened and fiberoptic intubation was planned. The patient was found to have an edematous larynx with difficulty passing the endotracheal tube through the vocal cords. The patient was noted to desaturate and subsequently became pulseless; CPR was initiated. Emergent crychothyroidotomy which was successfully performed however patient's end tidal and oxygen saturations remained flat. Bedside echo showed no cardiac activity and the patient unfortunately did not obtain ROSC. DISCUSSION: Anterior cervical discectomy and fusion is considered a relatively safe procedure, but can be related to catastrophic complications. Airway compromise requiring reintubation are rare, but have never been quantified. Potential causes of airway obstruction include pharyngeal edema, hematoma, cerebrospinal fluid leak and angioedema. Risk factors for airway complication include prolonged anesthetic time, extensive cervical dissections above C4 and estimated blood loss greater than 300 mL. The average time to respiratory insufficiency in these patients is 23 hours after surgery. Therefore, we suggest that intensive observation of respiratory function should be monitored for at least 48 hours following an anterior cervical discectomy and fusion procedure. CONCLUSIONS: This case shows that airway complications following anterior cervical discectomy and fusion can be catastrophic. This is a complication that all Pulmonary Critical Care physicians should be aware of. The above mentioned risk factors should be checked and intense observation of respiratory function should be monitored for at least 48 hours after surgery. Reference #1: Lim, S., Kesavabhotla, K., Cybulski, G. R., Dahdaleh, N. S., & Smith, Z. A. (2017). Predictors for Airway Complications Following Single- and Multilevel Anterior Cervical Discectomy and Fusion. Spine, 42(6), 379-384. Reference #2: Sagi, H. C., Beutler, W., Carroll, E., & Connolly, P. J. (2002). Airway Complications Associated With Surgery on the Anterior Cervical Spine. Spine, 27(9), 949-953 DISCLOSURES: No relevant relationships by Armand Golchin, source=Web Response No relevant relationships by William McGee, source=Web Response No relevant relationships by Mitchell Onwochei-Ashei, source=Web Response No relevant relationships by Quazi Kamran Uddin, source=Web Response

Efficacy and safety of anti-PD-1 antibody SHR-1210 combined with apatinib in patients with advanced triple-negative breast cancer.

1066 Background: PD-1/PD-L1 blockade monotherapy delivered positive outcomes in early-phase trials in advanced triple-negative breast cancer (TNBC). However, t he highest objective response rate (ORR) is 18.5%. IMPassion130 trial has demonstrated that only PD-L1+ TNBC had overall survival benefit from anti-PD-L1 antibody combined with chemotherapy. Preclinical studies found that antiangiogenic therapy could sensitize anti-PD-1 treatment via inducing PD-L1 expression and increasing CTLs infiltration in tumor microenvironment. Thus, we designed a phase II, open-label trial (NCT03394287) of SHR-1210 (anti-PD-1 antibody) in combination with apatinib (VEGFR2 inhibitor) in patients with advanced TNBC. Methods: 20-58 advanced TNBC patients whose systemic therapy lines in the metastatic setting was less than 3, will be randomly (1:1) enrolled from Sun Yat-sen Memorial Hospital to receive either SHR-1210 200mg Q2W plus apatinib 250mg, continuous dosing (d1-d14), or SHR-1210 200mg Q2W plus apatinib 250mg, intermittent dosing (d1-d7), until progression or unacceptable toxicities. Primary endpoint was ORR. Secondary end points included PFS, DCR, TTR, DoR, CBR, one year-OS and toxicity. Results: Until Jan 30, 2019, 34 patients were enrolled, 10 in the intermittent dosing arm, and 24 in the continuous dosing arm. 26 (76.5%) patients had prior systemic therapy in the metastatic setting. At the cutoff date (Jan 30, 2019), 28 patients were evaluable for ORR as per RECIST. The ORR was 47.4% (9 of 19) in the continuous dosing cohort, and no confirmed objective response was found in the intermittent dosing arm. The DCR was 68.4% in the continuous dosing arm, whereas it was 44.4% in the other arm. The median PFS was 2 months in the intermittent dosing cohort, while it was not reached in the continuous dosing cohort. The most common adverse events (AEs) was fatigue (65.0%), hand-foot syndrome (63.3%), and elevated aspartate aminotransferase and/or alanine aminotransferase (73.3%). There were no treatment-related deaths. Another 5 patients will be enrolled into the continuous dosing arm because of its favorable response. Conclusions: Anti-PD-1 antibody SHR-1210 combined with apatinib demonstrates favorable clinical activity and a manageable safety profile in patients with advanced TNBC. Clinical trial information: NCT03394287.

SAT-LB022 Effects of Intermittent Versus Continuous Phentermine Therapy on Weight Reduction and Inflammatory Markers in Obese Non-diabetic Patients

Introduction: Intermittent phentermine therapy has been proposed as an alternative to overcome tolerance associated with continuous daily use of phentermine to promote greater weight loss. Aim: To compare the effects of intermittent versus continuous phentermine therapy on weight reduction, cardiometabolic profile, inflammatory and anti-inflammatory markers in obese non-diabetic patients. Methods: Non-diabetic obese adults [body mass index (BMI) 27.5 to 35kg/m2] were recruited from obesity clinic. Eligible subjects were randomized to receive either continuous phentermine (30mg daily) or intermittent phentermine therapy (30mg daily for 4 weeks alternate with 2 weeks of treatment-free periods) for a total of 24 weeks, in addition to lifestyle modification (comprising of calorie restriction of 1200 kcal per day and at least 150 minutes per week of moderate intensity exercise). Primary endpoints were change in body weight from baseline as well as proportion of subjects losing at least 5% and 10% of baseline body weight at week 24 respectively. Results: Thirty-eight subjects [86.8% females, median age 36.5 years (interquartile range, IQR 32, 41.3), BMI 31.8kg/m2 (IQR 30.4, 33.4) and waist circumference 94.9cm (IQR 90.2, 99.1)] were randomised to either continuous (n=19) or intermittent phentermine arm (n=19). Fourteen subjects in the former and all in the latter completed the study. There were no significant differences in the degree of weight reduction [ - 7.3 kg (IQR - 10.1, - 3.4) vs - 9.7 kg (IQR -11.2, -7.2), p=0.10] as well as the proportion of subjects who achieved at least 5% and 10% of weight loss (78.9% vs 94.7%, p=0.34; 47.4% vs 73.7%, p=0.18 respectively) at week 24 in both arms. Nonetheless, intermittent phentermine therapy resulted in greater decrease in waist circumference while continuous phentermine therapy produced greater reduction in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hsCRP). Both regimes reduced the prevalence of insulin resistance and showed no difference in reduction of the proportion of subjects with high cardiovascular risk (as defined by hsCRP > 3mg/L). No significant between-group differences were seen in changes of blood pressure, pulse rate, glycaemic indices, lipids, adiponectin, binge eating scale scores and 36-item Short Form Survey version 2 (SF-36v2) scores. The most common side effects were dry mouth and insomnia. There was no difference in the occurrence of adverse events between the 2 treatment arms. Conclusion: Intermittent phentermine therapy is as effective as conventional daily phentermine treatment in promoting weight reduction while having similar side effect profile. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Fanning as an alternative to air conditioning – A sustainable solution for reducing indoor occupational heat stress

We assessed whether increasing airflow with an electric fan is similarly effective as decreasing air temperature with air cooling (AC) in preventing heat-related reductions in productivity, and elevations in body temperatures and discomfort in a warm/humid indoor environment. In 48 experimental trials, we compared the reduction in the human heat stress response of sixteen participants during 135 min of intermittent arm ergometry at a fixed heart rate of 110 beats min−1, from a simulated tropical environment (HOT; 30 °C, 70%RH; wind < 0.2 m s−1) to that observed with either a, (i) 7 °C reduction in air temperature (AC; 23 °C, 70%RH, wind < 0.2 m s−1); or (ii) facilitated airflow (FAN; 30 °C, 70%RH, wind = 4.2 m s−1). Cumulative work was similarly improved (+11%) by FAN compared to AC. Likewise, reductions in rectal temperature, thermal sensation, and thermal discomfort were similar with the two different cooling strategies. Sweat losses in the FAN trial were higher compared to AC but lower than HOT without fanning. In conclusion, fanning offers an effective method for alleviating thermal stress and preventing productivity losses for workers exposed to environmental heat. Moving air instead of chilling it may require a little more sweating, but it can save electricity and hence lower greenhouse gas emissions compared to AC.

Remote ischaemic preconditioning ameliorates sinus rhythm restoration rate through Cox maze radiofrequency procedure associated with inflammation reaction reduction.

Remote ischaemic preconditioning (RIPC) as adjuvant to selective heart surgery attenuates cardiac injury and atrial fibrillation (AF) occurrence. We investigated its effect on sinus rhythm (SR) restoration rate in permanent AF patients undergoing Cox maze (CM) radiofrequency ablation with concomitant mitral valve surgery. From May 2013 to May 2017, 206 patients with rheumatic valve disease concomitant with permanent AF were randomized to receive prosthesis valve replacement and CM radiofrequency ablation procedure with (n = 104) or without (n = 102) RIPC (intermittent arm ischaemia through three cycles of 5-min inflation, followed by 5-min deflation of a blood pressure cuff). The primary end point of the study was freedom from cumulative AF without using antiarrhythmic drugs 1year after operation; the secondary end points included inflammation reaction index over 48h postoperatively and clinical outcomes. Baseline characteristics and preoperative data did not differ between groups. The SR restoration rates were significantly higher in the RIPC group, 85.6%, 83.7%, and 82.7%, than those in the control group, 72.5%, 70.6%, and 69.6%, at discharge, 6months and 12months, respectively, after the radiofrequency ablation procedure (P < 0.05). The serum concentration of high sensitivity C-reactive protein and neutrophil-lymphocyte ratio were significantly decreased at 12h, 24h, and 48h postoperatively in the RIPC group compared to those in the control group (P < 0.05). RIPC induced by brief ischaemia and reperfusion of the arm ameliorated SR restoration rate in patients with permanent AF through CM radiofrequency ablation procedure and was associated with reduction of postoperative systemic inflammation reaction index.

Abstract NS5: Is the Extended Time Window Approach Safe in Pediatric AIS? Lessons Learned From 3 Cases

Background: Pediatric stroke is a rare but important cause of mortality and morbidity in this population. Endovascular therapy up to 24 hours after symptoms onset is beneficial in adults LVO acute ischemic stroke (AIS), but no safety or efficacy data of this approach is available for patients &lt;18. Methods and Results: We present three pediatric AIS cases (age 15-17) treated at GUH and WVU with endovascular techniques using extended time-window with selection based on perfusion criteria. Case 1 : 17 year old patient with history of Ebstein’s anomaly presented the day after a cardiac catheterization procedure with right hemiparesis and aphasia (NIHSS = 22). CTP identified left proximal ICA occlusion (ASPECTS score 7). Using the Penumbra device successful clot retrieval was achieved at 9:19 hours from onset. She was found to have a venous clot and right-to-left shunt from an atrial septal defect. 3 months mRS was 1. Case 2 : 17 y.o. female with 2 weeks history of intermittent right arm numbness presented with left hemiparesis and hemi-sensory loss (NIHSS 12). ER arrival time was 18:43 hours from the onset of sensory symptoms. CTP demonstrated complete right M1 occlusion secondary to right sub-clavian thrombus (ASPECTS score 8). Using the Solitaire stent retriever, recanalization was obtained at 20:05 hours after clinical onset. 3 months mRS was 1. Case 3 : 15 y.o female with Down syndrome, recently started on BCP woke up with right hemiparesis and aphasia (NIHSS = 22). MR perfusion demonstrated a distal M1/M2 clot with a large mismatch in the left MCA territory. Using a stent retriever device complete recanalization was obtained at 14:46 hours from the last time she was well. On the day of discharge her NIHSS was 7. Complete recanalization (TICI 3) was obtained in all three patients. No complications were observed during or following the procedure. NIHSS before and after the procedure improved by 11-to-17 points. Conclusions: A controlled study regarding endovascular approach in pediatric stroke is unlikely to occur. Therefore, case series must be reported in order to understand the safety of this approach. Strict patient selection and a team approach involving multiple pediatric and adult expertise are needed for a pediatric AIS response that includes endovascular intervention.

Systematic Review of Non-Conventional Dosing of Oral Anticancer Therapies in Malignant Haematology

IntroductionSurvival outcomes for patients with lymphoid, myeloid and plasma cell malignancies, have improved with the use of oral small molecule inhibitory agents. Oral anti-cancer therapies are often administered continuously and can have significant side-effects, which can adversely impact adherence, quality of life (QoL) and survival outcomes. In order to improve tolerability, non-standard dosing strategies are increasingly adopted in clinical practice; although, with limited guidance. A systematic review was conducted to identify evidence of, and outcomes from, non-conventional dosing of oral anti-cancer therapy in malignant haematology.MethodsA comprehensive search of all oral anti-cancer therapy listed in the British National Formulary for use to treat haematological malignancies was undertaken using the following databases: MEDLINE®, EMBASE®, and Cochrane Library©, and Cumulative Index to Nursing and Allied Health Literature (CINAHL©). The search was expanded using prospective citation chaining in the Web of Science and retrospective snowballing of reference lists of included studies to ensure a sensitive, comprehensive search. Studies were selected based on predefined inclusion/exclusion criteria, and were critically appraised. Extracted data were tabulated to summarise key findings, which were analysed by type of non-dosing strategy: dose interruption; dose reduction; and other dosing strategies.ResultsEleven studies were included and reviewed: two late phase clinical trials, four cohort studies, and five case reports. Findings from each included study (aim, design, treatment schdeule, reported efficacy/toxicty/QoL outcomes) are presented in the accompanying Table 1. These studies evaluated non-standard dosing of dasatinib, imatinib, lenalidomide and thalidomide. Four studies were conducted in Italy, four in the US, and one in Brazil, South Korea and UK. Dose reductions were the most commonly reported strategy (five studies). Two studies reported dose interruptions and four reported other dosing strategies. The quality of the studies ranged from moderate to high (e.g. clinical trials) to moderate to low (e.g. case reports).Russo et al (2015) conducted a single arm, open-label trial, in which the use of one month on/one month off schedule of imatinib was investigated in 96 CML patients aged ≥65 years. Although this trial did not report toxicity or QoL outcomes, there were no transformations (progressions) of CML to an accelerated or blast phase of disease using this alternative schedule. Therefore, results do not draw definitive conclusions that intermittent treatment can be offered to optimal and stable responders. However, they indicate a role for alternative treatment schedules tailored to individual patients, particularly those experiencing significant toxicities.Mangiacavalli et al (2012) investigated efficacy and adverse effects of a one-week interruption of thalidomide following daily administration for three weeks, compared to continuous therapy. Limited patient numbers (13 vs. 10) prevented this trial from obtaining definitive data regarding efficacy, but there was a trend for worse overall survival (OS, p< 0.001) and progression free survival (PFS, p=0.02) in the intermittent arm compared to the continuous one, with no difference in peripheral neuropathy.Dose reduction was reported in two imatinib retrospective cohort studies and three case reports (2 dasatinib, 1 imatinib). Results were inconclusive, primarily due to limitations in the design of the studies, small sample sizes and lack of detail in reporting toxicities and QoL outcomes. Lenalidomide was investigated in two small prospective cohort studies using alternate-day dosing in myelodysplastic syndrome and multiple myeloma. Toxicity outcomes were only reported in the myeloma study and QoL outcomes were reported in neither study.ConclusionsThis review identified limited evidence to support non-standard dosing strategies in malignant haematology. Imatinib dose interruption in optimally responsive CML patients warrants further investigation in large-scale, prospective, ideally blinded trials. DisclosuresDjebbari:Pfizer: Other: conference registration; Takeda: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding.

Abstract P5-18-01: Extended continuous vs intermittent adjuvant letrozole in postmenopausal women with lymph node-positive, early breast cancer (IBCSG 37-05/BIG 1-07 SOLE): Impact on patient-reported symptoms and quality of life

Abstract Background: SOLE efficacy results presented at ASCO 2017 showed that extended intermittent vs continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women who had received 4-6 years of adjuvant endocrine therapy for hormone-receptor positive (HR+), lymph-node positive breast cancer. Previous studies showed that the burden by symptoms related to endocrine therapy can be substantial. Even if symptoms improve during the treatment course, extending treatment implies continuation of symptoms. We compared differences in patient-reported symptoms (PRS) and quality of life (QoL) between extended continuous and intermittent letrozole over the first two years of trial treatment. Methods: From Nov 2007 to Dec 2010, 956 postmenopausal women who were disease-free following 4-6 years of prior adjuvant endocrine therapy for HR+, node-positive breast cancer were enrolled in the QoL substudy of the randomized phase III trial SOLE at selected centers. Patients receive extended continuous letrozole (2.5 mg daily) for 5 years or intermittent letrozole, taken for the first 9 months of years 1-4, and 12 months in year 5. 955 patients completed the 18-item Breast Cancer Prevention Trial (BCPT) Symptom Scales and further symptom-specific and global QoL indicators at baseline, and at 6, 12, 18 and 24 months after randomization. Differences in change of PRS and QoL from baseline between the two administration schedules were tested at 12 and 24 months for 8 symptom scales, 4 additional symptom and 4 global QoL indicators using mixed models with repeated measures. Results: Small changes in PRS and QoL scores were observed between baseline and 12 months after randomization, i.e. at the end of the first treatment-free interval in the intermittent arm. These changes showed a consistent pattern of greater worsening for patients receiving continuous compared to patients receiving intermittent letrozole. Patients receiving continuous letrozole reported a significantly greater worsening in vaginal problems (p&amp;lt;.02), musculoskeletal pain (p&amp;lt;.03), sleep disturbance (p&amp;lt;.01), physical wellbeing (p&amp;lt;.01) and mood (p&amp;lt;.03). At 24 months (after 2nd treatment-free interval) patients with intermittent letrozole reported a greater improvement in hot flushes (p&amp;lt;.03) than those with continuous letrozole. Changes in the other outcomes did not significantly differ between arms at 24 months. Conclusion: Although changes in PRS and QoL were small, there was a consistent pattern favoring the intermittent arm. For several symptoms and global QoL indicators, significantly less worsening was observed with the intermittent administration, mainly during the first year of extended treatment, due to small improvements during the treatment-free interval. Froma QoL perspective, women who suffer from endocrine side-effects in the extended setting may benefit from an intermittent administration. Citation Format: Ribi K, Luo W, Colleoni M, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Di Lauro V, Gomez HL, Ruhstaller T, Abdi E, Di Leo A, Müller B, Maibach R, Gelber RD, Goldhirsch A, Coates AS, Regan MM, Bernhard J. Extended continuous vs intermittent adjuvant letrozole in postmenopausal women with lymph node-positive, early breast cancer (IBCSG 37-05/BIG 1-07 SOLE): Impact on patient-reported symptoms and quality of life [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-18-01.