Vincent's Hospital Research Articles

Appropriateness of transthoracic echocardiography in preoperative elective joint arthroplasty patients.

Elective joint arthroplasty is a commonly performed procedure with postoperative cardiovascular complications occurring in up to 3% of elderly patients. Preoperative cardiac evaluation, including transthoracic echocardiography, may improve risk stratification and optimise perioperative outcomes in patients having non-cardiac surgery.This study aimed to investigate the frequency, indications, appropriateness and consequences of preoperative transthoracic echocardiography in elective joint arthroplasty patients. A one-year retrospective audit was conducted for patients who had elective joint arthroplasties performed at St Vincent's Hospital Melbourne. Patient demographics, transthoracic echocardiography indication, time between transthoracic echocardiography being ordered, performed and its impact on date of surgery were obtained via database and manual chart review. Appropriateness of transthoracic echocardiography was determined in accordance with international guidelines. This study analysed 609 elective joint arthroplasties. Of these, 116 (19%) already had a recent transthoracic echocardiography. Of the remaining 493 patients, 192 (39%) received a resting transthoracic echocardiography. Only 92 (48%) of the transthoracic echocardiography's ordered were deemed appropriate. Transthoracic echocardiography resulted in a significant delay of 31 days in time to surgery.This study indicates that almost 40% of elective joint arthroplasty patients with no recent echocardiogram are having a resting transthoracic echocardiography as part of their preoperative assessment. In 52% of cases, these are not clearly appropriate and result in delays to surgery.

Autologous Hematopoietic Stem Cell Transplantation (AHSCT) in Advanced, Treatment Refractory Multiple Sclerosis (MS) — a Phase II Clinical Trial

Aim: Ablation of auto-reactive immune cells followed by autologous hematopoietic stem cell transplantation (AHSCT) in the treatment of multiple sclerosis (MS) has been explored for the previous two decades. Morbidity and mortality rates originally limited referral for AHSCT in auto-immune disease but a reduction in treatment toxicity has facilitated increased clinical trials in the field. Here we present the outcomes of patients withadvanced, treatment refractory MS undergoing AHSCT in a Phase II study at our institute. We evaluate the safety and efficacy of AHSCT with intermediate-intensity immunosuppression in patients with highly aggressive MS.Methods: A single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS) commenced at St Vincent's Hospital in December 2010. Patients eligible for AHSCT had an Expanded Disability Status Scale (EDSS) of 2.0-7, had failed two prior disease-modifying therapies and displayed evidence of ongoing disease activity manifesting as clinical relapses and/or new MRI lesions in the year prior to AHSCT. CD34+ mobilisation with cyclophosphamide and G-CSF was performed, followed by conditioning with a BEAM (carmustine, etoposide, cytarabine, melphalan) + ATG (antithymocyte globulin) chemotherapeutic regimen. Patients underwent clinical assessment and peripheral blood collection for tissue banking at 3, 6, 12 months and yearly to 5 years. Gadolinium enhanced MRI was performed at 6, 12 months and yearly to 5 years. The primary outcomes were event-free survival and overall survival. Event free survival (EFS) was defined as no clinical or radiological relapses and no evidence of disability progression (by EDSS). Polychromic multi-parameter flow cytometry was performed for evaluation of post-transplant immune reconstitution.Results: Forty patients (26 with RRMS and 14 with SPMS) completed AHSCT, with a median follow-up of 24 months (range 3 to 63 months). Median EDSS prior to AHSCT was 6, with 17/40 having an EDSS >6, indicating a significant burden of neurologic disability. Patients were heavily pre-treated with immunosuppressive drugs (DMTs). Fifty-six percent of patients failed >4 disease modifying therapies prior to AHSCT with 2/3 having failed high efficacy treatment with Natalizumab (alpha-4 integrin inhibitor).Progression-free survival, clinical relapse-free survival (RFS), and MRI activity-free survival for the cohort were 80%, 90% and 95% respectively. Event free survival in the RRMS cohort was 90%. Sustained improvement in neurologic function by EDSS was seen in 15/40 (37.5%) of patients; 11 (42.3%) RRMS patients and 4 (28.6%) SPMS patients. MS quality of life score (MSQOL) - physical improved by 14.4 points (p=0.004) and MSQOL - mental improved by 10.3 points (p=0.08). Treatment related mortality was 0%. Adverse effects due to AHSCT were consistent with expected toxicities. One patient required admission to the intensive care unit in the post-transplant period due to serum sickness. There were no significant late neurologic adverse effects noted and no recorded cases of progressive multifocal leukoencephalopathy noted.Conclusion: The relapse-free survival (RFS) in our treatment refractory MS cohort undergoing AHSCT is significantly higher compared to RFS rates in MS patients treated with high-efficacy immunosuppressive therapies. Patients undergoing AHSCT at our institution had comparable rates of EFS to other recent prospective, single centre trials of AHSCT in spite of having higher baseline EDSS, greater evidence of pre-AHSCT disease activity, more heavily pre-treated (Burt et al. 2015, Atkins et al 2016) and use of a less aggressive conditioning regimen (Atkins et al. 2016). In summary, results of this phase II study suggest that AHSCT is effective in inducing sustained remission in the majority of aggressive RRMS and SPMS patients who failed multiple DMTs. DisclosuresNo relevant conflicts of interest to declare.

Fractalkine Treated of CD11b+CX3CR1+ Monocytes Promotes Angiogenesis through Pigment Epithelium-Derived Factor

Introduction: Myelo-monocytic cells expressing CD11b are involved in angiogenesis, but their specific roles and underlying mechanisms are unclear. We successfully identified a subset of CD11b+ monocytes expressing CX3CR1, the only receptor of fractalkine (Fkn; CX3CL1), in G-CSF mobilized peripheral blood stem cell collection (PBSC). We first verified Fkn triggers proangiogenic activities in CD11b+CX3CR1+ monocytes. Subsequently, we found that Fkn-treated CD11b+CX3CR1+ monocytes express pigment epithelium-derived factor (PEDF) once Fkn activates Fkn/CX3CR1 signaling. PEDF is a glycoprotein, which belongs to the serpin family and stimulates various physiologic processes such as angiogenesis, cell proliferation, and survival. In this study, we investigated the role of Fkn-treated CD11b+CX3CR1+ monocytes in angiogenesis and their mechanisms of action involving PEGF expression.Materialsand methods: To mobilize mononuclear cells (MNCs) including CD11b+CX3CR1+ monocytes into peripheral blood (PB), heathy donors were subcutaneously injected with G-CSF (10μg/kg) for 5 days. Apheresis MNCs were collected from donor PB using a COBE spectra cell separator (COBE, Lakewood, CO) after G-CSF injections. Then, CD11b+CX3CR1+cells were isolated by a MoFlo™ XDP Cell Sorter (Beckman Coulter, Brea, CA). HUVECs were isolated from human cords and cultured in either the presence or absence of Fkn-treated CD11b+CX3CR1+ monocytes, or their conditioned media (CM) on top of collagen at 37 °C in 5% CO2. For Fkn treatment, CD11b+CX3CR1+ monocytes were incubated with Fkn (50ng/mL) for 30 minutes. All procedures were approved by the Institutional Review Board at St. Vincent's Hospital, the Catholic University of Korea. All clinical samples were obtained from donors with informed consent.Results: CD11b+CX3CR1+ monocytes were found at 19.6±3.58% of total MNCs in human G-CSF mobilized PBSC. They expressed CD14 and CD16, which are common markers for human monocytes. The average number of CD11b+CX3CR1+ monocytes collected from one apheresis was 9.2±1.2X109. Administration of Fkn (50ng/mL for 30 minutes) in vitro greatly enhanced the angiogenic potential of CD11b+CX3CR1+ monocytes on HUVECs. CM harvested from Fkn-treated CD11b+CX3CR1+ monocytes showed equivalent effects to that of Fkn-treated CD11b+CX3CR1+ monocytes. Their high angiogenic potential is largely attributed to increased expression of PEDF according to angiogenic protein array results, and treating Fkn-treated CD11b+CX3CR1+ monocytes with a specific PEDF inhibitor largely abrogated HUVEC proliferation and vascular structure formation compared to control (p <0.001).Conclusion: We were able to collect enough CD11b+CX3CR1+ monocytes from G-CSF mobilized PBSC. High angiogenic potential of Fkn-treated CD11b+CX3CR1+ monocytes is largely attributed to increased expression of PEDF. Thus, G-CSF mobilization of CD11b+CX3CR1+ monocytes and subsequent Fkn treatment of the monocytes may be a novel therapeutic approach to translate to clinical utility in order to accelerate recovery of blood perfusion in ischemic diseases. DisclosuresNo relevant conflicts of interest to declare.

Seizure likelihood varies with day-to-day variations in sleep duration in patients with refractory focal epilepsy: A longitudinal electroencephalography investigation.

BackgroundWhile the effects of prolonged sleep deprivation (≥24 h) on seizure occurrence has been thoroughly explored, little is known about the effects of day-to-day variations in the duration and quality of sleep on seizure probability. A better understanding of the interaction between sleep and seizures may help to improve seizure management.MethodsTo explore how sleep and epileptic seizures are associated, we analysed continuous intracranial electroencephalography (EEG) recordings collected from 10 patients with refractory focal epilepsy undergoing ordinary life activities between 2010 and 2012 from three clinical centres (Austin Health, The Royal Melbourne Hospital, and St Vincent's Hospital of the Melbourne University Epilepsy Group). A total of 4340 days of sleep-wake data were analysed (average 434 days per patient). EEG data were sleep scored using a semi-automated machine learning approach into wake, stages one, two, and three non-rapid eye movement sleep, and rapid eye movement sleep categories.FindingsSeizure probability changes with day-to-day variations in sleep duration. Logistic regression models revealed that an increase in sleep duration, by 1·66 ± 0·52 h, lowered the odds of seizure by 27% in the following 48 h. Following a seizure, patients slept for longer durations and if a seizure occurred during sleep, then sleep quality was also reduced with increased time spent aroused from sleep and reduced rapid eye movement sleep.InterpretationOur results suggest that day-to-day deviations from regular sleep duration correlates with changes in seizure probability. Sleeping longer, by 1·66 ± 0·52 h, may offer protective effects for patients with refractory focal epilepsy, reducing seizure risk. Furthermore, the occurrence of a seizure may disrupt sleep patterns by elongating sleep and, if the seizure occurs during sleep, reducing its quality.

Reflux Esophagitis and Fatigue: Are They Related?

Gastroesophageal reflux disease (GERD) is a chronic, recurrent disease. Reflux esophagitis can interfere with sleep via acid reflux, which can cause daytime sleepiness or fatigue. However, little is known about the association between reflux esophagitis and fatigue. Objectives: We evaluated the association between fatigue and reflux esophagitis in subjects seen at health check-ups. Methods: Consecutive patients who were scheduled for screening endoscopies were enrolled prospectively at the Comprehensive Medical Examination Center of St. Vincent Hospital and Eunpyeong St. Mary’s Hospital, Korea. Three validated questionnaires were used to assess fatigue, daytime hypersomnolence, anxiety, and depression: the Multidimensional Fatigue Inventory—Korean version (MFI-K), Epworth Sleepiness Scale (ESS), and Hospital Anxiety and Depression Scale (HADS). Results: We investigated 497 consecutive eligible subjects. The reflux esophagitis and symptomatic GERD groups comprised 103 (20.7%) and 92 (18.5%) subjects, respectively. The MFI-K total, ESS, HADS-anxiety, and HADS-depression scores did not differ between the esophagitis and non-esophagitis groups (50.0 ± 11.5 vs. 49.7 ± 10.9, p = 0.661; 6.2 ± 2.8 vs. 6.1 ± 3.1, p = 0.987; 5.8 ± 3.1 vs. 5.2 ± 3.2, p = 0.060; 6.2 ± 3.6 vs. 6.0 ± 3.3, p = 0.561). However, the MFI-K total, ESS, HADS-anxiety, and HADS-depression scores were higher in the symptomatic group than in the non-symptomatic group (54.7 ± 12.7 vs. 48.6 ± 10.3, p < 0.001; 7.1 ± 3.5 vs. 5.9 ± 2.9, p = 0.002; 6.4 ± 3.3 vs. 5.1 ± 3.1, p < 0.001; 7.5 ± 4.0 vs. 5.7 ± 3.1, p < 0.001). Multiple regression analysis showed that the MFI-K total was correlated with GERD symptoms (p = 0.021), women (p = 0.001), anxiety (p < 0.001), and depression (p < 0.001). Conclusion: There was no statistically significant association in which reflux esophagitis could cause daytime sleepiness, fatigue, anxiety, or depression. However, fatigue was associated with GERD symptoms, women, anxiety, and depression. Further studies should clarify the association between fatigue and reflux esophagitis.

Novel Measurements of Respiratory System Mechanics Demonstrate Important Features of Donor-Recipient Lung Volume Matching That May Link to Subsequent Chronic Lung Allograft Dysfunction

<h3>Purpose</h3> The effect of matching donor and lung transplant (LTx) recipient lung volumes on LTx outcomes is unknown. The Forced Oscillation Technique (FOT) is a simple measure of the mechanical properties of the respiratory system. We have recently developed novel measures of airway closure using FOT. This study aims to assess the effect of matching donor and recipient lung volumes on respiratory system mechanics using FOT. <h3>Methods</h3> A multi-centre (Alfred Hospital, Melbourne and St Vincent's Hospital, Sydney) prospective study of (n=19) subjects (63% male, age 56 ±13yrs) at one time point 3-6 months post bilateral LTx were divided into two groups: G1 - Recipient measured pre-LTx total lung capacity (rTLC) < predicted donor TLC (dTLC) n=9; G2 - rTLC > predicted dTLC, n=10. All subjects underwent pulmonary function testing including, spirometry, plethysmography and FOT (Tremoflo 2000, Thorasys, Canada). <h3>Results</h3> In G1, respiratory system elastance (stiffness=AX5) positively correlated with difference between dTLC and rTLC (p<0.01, r²=0.45) in non-obstructed subjects (<b>Figure 1A)</b>; i.e. implanting oversized lungs increases respiratory system stiffness. In G2, airway closure occurred at a higher lung volume as size mismatching increased (p<0.01, r²=0.37); i.e. implanting undersized lungs can increase airway closure (<b>Figure 1B</b>). <h3>Conclusion</h3> Novel measurements of respiratory mechanics from FOT demonstrate both oversizing and under-sizing donor TLC can alter recipient respiratory mechanics post-LTx. Longitudinal studies are underway to correlate these effects with the incidence and extent of baseline or chronic lung allograft dysfunction (BLAD & CLAD).

The Rope

The Rope

Optimal Blood Glucose Monitoring Interval for Insulin Infusion in Critically Ill Non-Cardiothoracic Patients: A Pilot Study.

Objective:The American Diabetes Association and the Society of Critical Care Medicine recommend monitoring blood glucose (BG) every 1-2 hours in patients receiving insulin infusion to guide titration of insulin infusion to maintain serum glucose in the target range; however, this is based on weak evidence. We evaluated the compliance of hourly BG monitoring and relation of less frequent BG monitoring to glycemic status.Materials and Methods:Retrospective chart review performed on 56 consecutive adult patients who received intravenous insulin infusion for persistent hyperglycemia in the ICU at Saint Vincent Hospital, a tertiary care community hospital an urban setting in Northeast region of USA. The frequency of fingerstick blood glucose (FSBG) readings was reviewed for compliance with hourly FSBG monitoring per protocol and the impact of FSBG testing at different time intervals on the glycemic status. Depending on time interval of FSBG monitoring, the data was divided into three groups: Group A (<90 min), Group B (91-179 min) and Group C (≥180 min).Results:The mean age was 69 years (48% were males), 77% patients had preexisting type 2 diabetes mellitus (T2DM). The mean MPM II score was 41. Of the 1411 readings for BG monitoring on insulin infusion, 467 (33%) were in group A, 806 (57%) in group B and 138 (10%) in group C; hourly BG monitoring compliance was 12.6%. The overall glycemic status was similar among all groups. There were 14 (0.99%) hypoglycemic episodes observed. The rate of hypoglycemic episodes was similar in all three groups (p=0.55).Conclusion:In patients requiring insulin infusion for sustained hyperglycemia in ICU, the risk of hypoglycemic episodes was not significantly different with less frequent BG monitoring. The compliance to hourly blood glucose monitoring and ICU was variable, and hypoglycemic episodes were similar across the groups despite the variation in monitoring.Significance of the Study:The importance of glycemic control in ICU has been well established and it is a resource intensive venture. However, there are no major studies highlighting the most optimal time interval for blood glucose checks in critically ill patients on insulin infusion. With this study we hypothesize that time duration between blood glucose checks can be increased safely without any untoward effects. Our study provides evidence for effective resource management with reducing the time spent with every glucose check and directly translating into high value care.

375. COVID 19 infection in a Massachusetts community hospital

BackgroundThe ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has led to 105690 cases and 7647 deaths in Massachusetts as of June 16.MethodsThe study was conducted at Saint Vincent Hospital, an academic health medical center in Worcester, Massachusetts. The institutional review board approved this case series as minimal-risk research using data collected for routine clinical practice and waived the requirement for informed consent. All consecutive patients who were sufficiently medically ill to require hospital admission with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample were included.ResultsA total of 109 consecutive patients with COVID 19 were admitted between March 15 and May 31. Sixty one percent were men, the mean age of the cohort was 67. Forty one patients (37%) were transferred from nursing homes. Twenty seven patients died (24%) and the majority of the dead patients were men (62%). Fifty one patients (46%) required admission to the medical intensive care unit and 34 necessitated mechanical ventilation, twenty two patients on mechanical ventilation died (63%). The most common co-morbidities were essential hypertension (65%), obesity (60%), diabetes (33%), chronic kidney disease (22%), morbid obesity (11%), congestive heart failure (16%) and COPD (14%). Five patients required hemodialysis. Fifty five patients received hydroxychloroquine, 24 received tocilizumab, 20 received convalescent plasma and 16 received remdesivir. COVID 19 appeared in China in late 2019 and was declared a pandemic by the World Health Organization on March 11, 2020. Our study showed a high mortality in patients requiring mechanical ventilation (43%) as opposed to those who did not (5.7%). Hypertension, diabetes and obesity were highly prevalent in this aging population. Our cohort was too small to explore the impact of treatment with remdesivir, tocilizumab or convalescent plasma.ConclusionIn this cohort obesity, diabetes and essential hypertension are risk factors associated with high mortality. Patients admitted to the intensive care unit who need mechanical ventilation have a mortality approaching 50 %.Disclosures All Authors: No reported disclosures

Endoscopic features of buried Barrett’s mucosa

Buried Barrett's mucosa is defined as intestinal metaplasia that is "buried" under the normal-appearing squamous epithelium. This can occur in Barrett's esophagus with or without previous endoscopic therapy. Dysplasia and neoplasia within buried Barrett's mucosa have also been reported. However, endoscopic features of buried Barrett's mucosa have not been described. At our tertiary referral center for Barrett's esophagus, several endoscopic features have been observed in patients who were found to have buried Barrett's mucosa on histology. These features are squamous epithelium which is (1) darker pink on white-light and darker brown on narrow-band imaging and/or (2) has a slightly raised or nodular appearance. It was also observed that either of these 2 features is frequently seen adjacent to a Barrett's mucosa island. This study aimed to (1) evaluate the diagnostic accuracy of these endoscopic features, and (2) evaluate the frequency of endoscopically identifiable buried Barrett's mucosa in patients with dysplastic Barrett's esophagus, before and after endoscopic eradication therapy. This was a retrospective analysis of a prospectively observed cohort of all cases of dysplastic Barrett's esophagus referred to St Vincent's Hospital, Melbourne. Endoscopy documentation software and histopathology reports of esophageal biopsy and EMR specimens between March 2013 and March 2019 were searched for terms "buried" or "subsquamous" Barrett's mucosa. Endoscopic reports, images, and histopathology reports of suspected buried Barrett's mucosa were then reviewed to apply the endoscopic features and correlate with the histologic diagnosis. In a cohort of 506 patients with dysplastic Barrett's esophagus, 33 (7%) patients (73% male, median age at referral 70.5 years) had buried Barrett's mucosa on histology. Twenty-seven (82%) patients had previous treatment for dysplastic Barrett's esophagus; radiofrequency in 2 (6%), EMR in 4 (12%), and both modalities in 21 (64%). Six (18%) had no previous treatment. Histologically confirmed buried Barrett's mucosa was suspected at endoscopy in 26 patients (79%). Endoscopic features were (1) darker pink or darker brown mucosa underneath squamous epithelium (24%), (2) raised areas underneath squamous mucosa (27%), and both features present concurrently (27%). These features were associated with adjacent islands of Barrett's esophagus in 48%. Forty-four cases of buried Barrett's mucosa were suspected endoscopically, and these were sampled by biopsy (50%) and EMR (50%). Buried Barrett's mucosa was confirmed in 26 cases, with a positive predictive value of endoscopic suspicion of 59%. Eighteen cases of endoscopically suspected buried Barrett's mucosa had no buried Barrett's mucosa on histology; inflammation or reflux was identified in 12 (67%) patients. Dysplasia was identified within buried Barrett's mucosa in 12 (36%) patients; 5 intramucosal adenocarcinoma, 1 high-grade dysplasia, and 6 low-grade dysplasia. Endoscopic features of buried Barrett's mucosa were observed in 11 of 12 cases harboring dysplasia or neoplasia, compared with 15 of 21 cases of buried Barrett's mucosa without dysplasia. In this retrospective analysis of prospectively observed patients with dysplastic Barrett's esophagus, buried Barrett's mucosa was identified in 7%, including treatment-naive patients. The proposed endoscopic features of buried Barrett's mucosa were seen in 79% of patients with histology confirmed disease. These endoscopic features may predict the presence of buried Barrett's mucosa, which may contain dysplasia or neoplasia. An overlap between the endoscopic features of inflammation, reflux, and buried Barrett's mucosa was observed. Future prospective studies are required to develop and validate endoscopic criteria for identifying buried Barrett's mucosa.

Denosumab-Related Osteonecrosis of the Jaw May Not Be a Subject of Teriparatide Treatment

Journal of Bone and Mineral ResearchEarly View Letter to the Editor Denosumab-Related Osteonecrosis of the Jaw May Not Be a Subject of Teriparatide Treatment Kyung-Su Park, Corresponding Author Kyung-Su Park pkyungsu@catholic.ac.kr orcid.org/0000-0003-0020-003X Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea Address correspondence to: Kyung-Su Park, MD, Division of Rheumatology, Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea College of Medicine, 93, Jungbu-daero, Paldal-gu, Suwon, Gyeonggi-do, 16247, South Korea. E-mail: pkyungsu@catholic.ac.kr Contribution: Conceptualization, Methodology, Project administration, Supervision, Writing - original draft, Writing - review & editingSearch for more papers by this authorSeung Min Jung, Seung Min Jung Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea Contribution: Conceptualization, Writing - review & editingSearch for more papers by this authorYune-Jung Park, Yune-Jung Park Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea Contribution: Conceptualization, Writing - review & editingSearch for more papers by this authorKi-Jo Kim, Ki-Jo Kim Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea Contribution: Conceptualization, Writing - review & editingSearch for more papers by this author Kyung-Su Park, Corresponding Author Kyung-Su Park pkyungsu@catholic.ac.kr orcid.org/0000-0003-0020-003X Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea Address correspondence to: Kyung-Su Park, MD, Division of Rheumatology, Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea College of Medicine, 93, Jungbu-daero, Paldal-gu, Suwon, Gyeonggi-do, 16247, South Korea. E-mail: pkyungsu@catholic.ac.kr Contribution: Conceptualization, Methodology, Project administration, Supervision, Writing - original draft, Writing - review & editingSearch for more papers by this authorSeung Min Jung, Seung Min Jung Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea Contribution: Conceptualization, Writing - review & editingSearch for more papers by this authorYune-Jung Park, Yune-Jung Park Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea Contribution: Conceptualization, Writing - review & editingSearch for more papers by this authorKi-Jo Kim, Ki-Jo Kim Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea Contribution: Conceptualization, Writing - review & editingSearch for more papers by this author First published: 25 June 2022 https://doi.org/10.1002/jbmr.4625Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

Nicotine replacement treatment, e-cigarettes and an online behavioural intervention to reduce relapse in recent ex-smokers: a multinational four-arm RCT.

Relapse remains an unresolved issue in smoking cessation. Extended stop smoking medication use can help, but uptake is low and several behavioural relapse prevention interventions have been found to be ineffective. However, opportunistic 'emergency' use of fast-acting nicotine replacement treatment or electronic cigarettes may be more attractive and effective, and an online behavioural Structured Planning and Prompting Protocol has shown promise. The present trial aimed to evaluate the clinical effectiveness and cost-effectiveness of these two interventions. A randomised controlled trial. English stop smoking services and Australian quitlines, Australian social media and St Vincent's Hospital Melbourne, Fitzroy, VIC. Ex-smokers abstinent for at least 4 weeks, with some participants in Australia also recruited from 1 week post quit date. The planned sample size was 1400, but the trial was curtailed when 235 participants were recruited. Participants were randomised in permuted blocks of random sizes to (1) oral nicotine replacement treatment/electronic cigarettes to use if at risk of relapse, plus static text messages (n = 60), (2) the Structured Planning and Prompting Protocol and interactive text messages (n = 57), (3) oral nicotine replacement treatment/electronic cigarettes plus the Structured Planning and Prompting Protocol with interactive text messages (n = 58) or (4) usual care plus static text messages (n = 59). Owing to delays in study set-up and recruitment issues, the study was curtailed and the primary outcome was revised. The original objective was to determine whether or not the two interventions, together or separately, reduced relapse rates at 12 months compared with usual care. The revised primary objective was to determine whether or not number of interventions received (i.e. none, one or two) affects relapse rate at 6 months (not biochemically validated because of study curtailment). Relapse was defined as smoking on at least 7 consecutive days, or any smoking in the last month at final follow-up for both the original and curtailed outcomes. Participants with missing outcome data were included as smokers. Secondary outcomes included sustained abstinence (i.e. no more than five cigarettes smoked over the 6 months), nicotine product preferences (e.g. electronic cigarettes or nicotine replacement treatment) and Structured Planning and Prompting Protocol coping strategies used. Two substudies assessed reactions to interventions quantitatively and qualitatively. The trial statistician remained blinded until analysis was complete. The 6-month relapse rates were 60.0%, 43.5% and 49.2% in the usual-care arm, one-intervention arm and the two-intervention arm, respectively (p = 0.11). Sustained abstinence rates were 41.7%, 54.8% and 50.9%, respectively (p = 0.17). Electronic cigarettes were chosen more frequently than nicotine replacement treatment in Australia (71.1% vs. 29.0%; p = 0.001), but not in England (54.0% vs. 46.0%; p = 0.57). Of participants allocated to nicotine products, 23.1% were using them daily at 6 months. The online intervention received positive ratings from 63% of participants at 6 months, but the majority of participants (72%) completed one assessment only. Coping strategies taught in the Structured Planning and Prompting Protocol were used with similar frequency in all study arms, suggesting that these are strategies people had already acquired. Only one participant used the interactive texting, and interactive and static messages received virtually identical ratings. The inability to recruit sufficient participants resulted in a lack of power to detect clinically relevant differences. Self-reported abstinence was not biochemically validated in the curtailed trial, and the ecological momentary assessment substudy was perceived by some as an intervention. Recruiting recent ex-smokers into an interventional study proved problematic. Both interventions were well received and safe. Combining the interventions did not surpass the effects of each intervention alone. There was a trend in favour of single interventions reducing relapse, but it did not reach significance and there are reasons to interpret the trend with caution. Further studies of both interventions are warranted, using simpler study designs. Current Controlled Trials ISRCTN11111428. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 68. See the NIHR Journals Library website for further project information. Funding was also provided by the National Health and Medical Research Council, Canberra, ACT, Australia (NHMRC APP1095880). Public Health England provided the funds to purchase the nicotine products in England.

Sarcopenia Is Associated With Reduced Function on Admission to Rehabilitation in Patients With Diabetes.

This work aims to estimate the prevalence of sarcopenia and to investigate the association between sarcopenia and functional performance in patients with and without diabetes admitted for inpatient rehabilitation. Consecutive patients admitted to the subacute inpatient rehabilitation unit at St Vincent's Hospital Melbourne, Australia (November 2016 to March 2020) were prospectively recruited into this cross-sectional study. Sarcopenia was diagnosed using the European Working Group on Sarcopenia in Older People 2018 algorithm. Participants' functional performance was measured by the total Functional Independence Measure, motor Functional Independence Measure, and the Short Physical Performance Battery. The association between sarcopenia and functional performance was investigated using quantile regression. Of 300 participants, 49 (16%) had a history of diabetes and 44 (14.7%) were diagnosed with sarcopenia. No significant difference in the prevalence of sarcopenia between patients with or without diabetes was identified (11/49, 22.5% vs 33/251, 13.2%, P = .12). In patients with diabetes, those with sarcopenia had significantly reduced functional performance compared to those without sarcopenia on Functional Independence Measure, motor Functional Independence Measure, and the Short Physical Performance Battery, whereas in patients without diabetes no significant difference between patients with and without sarcopenia were identified for either functional performance measure (all P values for interaction < .005). The diagnosis of sarcopenia was associated with a reduced functional performance on admission to inpatient rehabilitation in patients with diabetes, but not in those without diabetes. Further investigation is needed into the progress of patients with dual diagnoses of diabetes and sarcopenia in inpatient rehabilitation.

A Shared Electronic Health Record in a Rural Setting Maintains Hematological Cancer Services Remotely during the COVID-19 Pandemic

IntroductionThe COVID-19 pandemic has had drastic effects on healthcare provision across Australia and the world. Rural hematology patients who may rely on visiting medical officers from larger cities or long distance travel for reviews are particularly vulnerable to having their treatment affected by the recent changes to healthcare delivery given severe travel restrictions.The Griffith Hematology/Oncology Unit is based in Griffith Base Hospital, a regional hospital in New South Wales, Australia. It is serviced by consultant hematologists from St Vincent's Hospital at the capital city of Sydney, Australia, who visit fortnightly to run hematology outreach clinics and supervise chemotherapy delivery. Griffith is located 575km from Sydney and has an estimated population of over 26,000(1). The COVID-19 pandemic imposed significant travel restrictions, such that visiting haematologists have been unable to travel to continue in-person clinics since April 2020. This has led to the exclusive reliance on telemedicine (telehealth and telephone reviews) and remote chemotherapy delivery supervision. Having an electronic health record (EHR) containing all relevant patient information which is remotely accessible to treating physicians has been integral to the continuity of comprehensive specialist cancer care in this rural setting via telemedicine.MethodsThe previously reported shared EHR between Griffith and St Vincent's Hospital, Sydney was used to review the impact of COVID-19 on service delivery in Griffith(2). All rural patient information was accessible from the metropolitan location including comprehensive documentation of a patient's clinical findings, routine observations, diagnostic pathology and radiology results, and details of treatment at the Griffith site. Remote chemotherapy prescribing and telemedicine notes were documented through the EHR.ResultsThe number of new referrals, follow ups and total patients over the four months prior to the COVID-19 related changes (December 2019 to March 2020) and the four months following (April to July 2020) were compared. From April 2020 onwards, the Griffith clinic patients underwent reviews via telemedicine or telephone with no in-person reviews able to be conducted in Griffith due to the travel restrictions. The number of new referrals, follows up visits and the total number of patients seen following the change to telemedicine had all increased with no reduction in service delivery seen (Table 1). The total number of patient reviews was 167 visits over the four months prior to the change, which increased to 186 reviews after the travel restrictions were applied.Despite the travel restrictions, the hematology outreach services to Griffith were maintained through telemedicine reviews in a similar manner to the metropolitan service. Griffith rural hematology patients continue to undergo regular telemedicine reviews with monitoring of laboratory and imaging results through the EHR, receiving the same level of care as metropolitan patients.Chemotherapy is still able to be prescribed, adjusted and reviewed from the Sydney location for all patients. The total number of chemotherapy treatment cycles delivered in Griffith only slightly decreased despite the changes to service provision, which was attributed to normal variation in patients requiring treatment over 2020 (Table 2). 32 chemotherapy treatment cycles were delivered prior to the change compared to 26 cycles following, for the primary indications of lymphoma and myeloma.ConclusionIn recent months, the centralised EHR has proven critical in minimising clinical service disruptions caused by the COVID-19 pandemic by facilitating telemedicine links and remote patient management. We demonstrate how the shared EHR has been integral to the continuation of complex rural patient management during the COVID-19 pandemic due to the availability of remotely accessible patient information and chemotherapy prescribing. No significant change in clinical service activity was seen following the drastic travel restrictions due to the pandemic. Given these travel restrictions are expected to continue, it is encouraging that the shared EHR will allow rural Griffith patients continued access to appropriate specialist hematology care over the coming months. This work demonstrates how an EHR is fundamental to the sustainability of vital cancer services for rural communities.DisclosuresHamad:Abbvie: Honoraria; Novartis: Honoraria.

Weekly Cyclophosphamide, Subcutaneous Bortezomib and Dexamethathasone (CyBorD) for Initial Treatment of Transplant Eligible Patients with Multiple Myeloma: Experience of Two Transplant Centres

Introduction: Induction regimens utilising cyclophosphamide, bortezomib and dexamethasone (CyBorD) prior to autologous stem cell transplant are utilised worldwide where access to a combination immunomodulatory agent/proteasome inhibitor approach is limited due to financial or regulatory constraints. Protocols utilising weekly subcutaneous bortezomib are favoured in order to reduce toxicity, but there is a lack of published data regarding response rates and survival using this approach. Methods: We identified all patients treated between August 2015 and August 2019 at St Vincent's Hospital and January 2012 and August 2019 at Liverpool Hospital in Sydney, Australia who were prescribed four 28 day cycles of CyBorD (subcutaneous bortezomib 1.3mg/m2, cyclophosphamide 300mg/m2 (or 500mg) and dexamethasone 40mg (day 1, 8, 15 and 22) for newly diagnosed MM with an intent to proceed to ASCT. Results: The baseline patient and disease characteristics of the 70 eligible patients are listed in Table 1. Most patients received therapy as planned (62/70) and all but one proceeded to ASCT. Seven patients had additional therapy after 4 cycles of CyBorD due to inadequate response. Best response to CyBorD induction included stable disease (SD) in 16 (23%) partial response (PR) in 30 (43%), and a VGPR or better in 24 (33%) (2 complete response (CR)). No patient had progressive disease. All but one patient had successful stem cell mobilisation. The median number of collection days was 2 (range 1-4) and median number of stem cells collected was 10.4 x 106/kg. 6 patients required plerixafor. The one patient who could not be mobilised received lenalidomide prior to mobilisation. Best response post ASCT (n = 69) prior to unplanned therapy included SD in 2 (3%), PR in 25 (35%), ≥ VGPR in 41 (59%) (4 patients with CR) and undetermined in 1. Of those who had SD following induction, 4 achieved a ≥ VGPR following ASCT, 9 had a PR, 2 had SD and 1 did not undergo ASCT. Five patients underwent a second ASCT due to inadequate response. 37 patients received maintenance. After a median of 3 years follow-up, 12 patients (17%) had died (10 from progressive disease) and 28 (40%) had progressed. Overall survival at 1 year was 100% and 3 years was 85% (95% CI 71-93%) (Figure 1). Progression free survival at 1 year was 92% (95% CI 88-97%) and 3 years was 46% (95% CI 31-60%) (Figure 1). There were no deaths during induction and no documented bortezomib dose reductions. 16 of 70 patients had unplanned hospital admissions during induction. There was no transplant related mortality. Conclusions: To our knowledge, this is the largest study evaluating use of a weekly induction protocol of subcutcutaneous bortezomib, oral cyclosphosphamide and oral dexamethasone in transplant eligible MM. It shows comparable response rates and survival outcomes to other retrospective studies and documented toxicity was low. This induction protocol remains standard of care in many countries, in particular where financial constraints limit use of combined IMID/PI induction and this study confirms the efficacy and tolerability of this commonly used protocol. Disclosures Ling: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene BMS: Membership on an entity's Board of Directors or advisory committees; Specialised Therapeutics: Honoraria.

Multicenter, Retrospective Evaluation of Therapeutic Efficacy of Ruxolitinib for Chronic Gvhd Treatment

Background Several agents have been investigated for beyond second-line treatment of chronic graft-versus-host disease (GVHD). Ruxolitinib has been recently approved for steroid-refractory acute GVHD, while a prospective randomized study is ongoing to examine its efficacy in steroid-resistant chronic GVHD (cGVHD). The present study evaluated the efficacy of Ruxolitinib in terms of 1) overall response rate (ORR), 2) clinical benefit (CB), 3) dose reduction of corticosteroid exposure, 4) failure-free survival (FFS) and 5) overall survival (OS), in patients heavily pretreated for steroid-resistant cGVHD. Patients and methods A total of 47 patients who developed cGVHD after HCT and treated with Ruxolitinib for cGVHD from March 2016 to April 2020, at three different sites (Princess Margaret Cancer Center, Canada; Vancouver General Hospital, Canada and Saint Vincent Hospital, Australia), were evaluated in the retrospective study. Patients and disease characteristics are as follows: median age 52 years; classical 35 (71%), overlap syndrome 14 (29%). Of note, 27 patients (57.4%) had a previous history of acute GVHD. The ORR and CB were assessed at months 3, 6 and 12, retrospectively. Responses were evaluated according to NIH scoring/staging/response assessment as part of standard clinical practice. CB was assessed considering clinical response as well as steroid dose reduction. For systemic steroid dose reduction, prednisone dose per kg per day was captured prior to Ruxolitinib start, at months 3, 6 and 12. Treatment failure was defined as 1) resistance requiring treatment switch, 2) non-relapse mortality (NRM), 3) relapse, 4) intolerance to treatment. FFS and OS were calculated from the day of starting Ruxolitinib therapy for cGVHD treatment. Results A total of 47 patients had moderate (11/47, 24.4%) to severe (33/47, 73.3%) cGVHD except one who had mild grade cGVHD with a high-risk feature (thrombocytopenia at the time of Ruxolitinib start). The median number of organ involvement was 3 (range 1-7). Over half of patients (63.8%) received Ruxolitinib as 4th line or beyond for cGVHD treatment, while median number of previous lines of therapy was 3 (range 1-9). All 47 patients (100%) had been previously treated with systemic steroids; other previous treatments included ECP therapy (53.2%), Imatinib (29.8%), Ibrutinib (23.4%), Rituximab (21.3%). Ruxolitinib was started at 10-15 mg daily as initial dose, then maintained at 20mg daily in two divided doses on months 3, 6 and 12.With a median follow-up duration of 12 months, ORR was attained in 35.7%, 36.0% and 35.0% at 3, 6 and 12 months, respectively (Figure A). Of note, ORR in patients with sclerotic changes was 56%, and 61.5% in those with lung involvement. Patients resistant to TKI (i.e. Imatinib or Ibrutinib) for cGVHD treatment showed similar ORR compared to those naïve to TKI therapy.The CB was observed in 53.5%, 66.7% and 72.2% at months 3, 6 and 12, respectively (Figure B). Patients resistant to TKI for cGVHD treatment did not show any difference in CB compared to those naïve to TKI therapy.In terms of prednisone dose reduction, by 12 months , half of patients (50.0%) could taper prednisone doses below 0.1mg/kg/day, while the proportion of patients on prednisone dose below 0.1mg/kg/day was 9.3%, 20.0%, 17.4%, and 50.0% at month 0, 3, 6 and 12, respectively (Figure C). The group who achieved CB at 3 months showed a significantly lower dose of prednisone at 12 months (0.078mg/kg/day) compared to those without clinical benefit at 3 months (0.197mg/kg/day; p=0.033; Figure D).Out of 37 patients evaluated, 11 failures (29.7%) were noted, including resistance requiring a switch to other therapy (n=7), NRM (n=2) and intolerance (n=2). The FFS rate at 1 year in the overall population was 68.5% (Figure E). The FFS at 1 year in those having CB at 3 months vs not was 86.5% vs 51.4% (p=0.025).The OS at 1 year was 90.9% (Figure F). The OS at 1 year in those having a CB at 3 months vs not was 100% vs 78.8% (p=0.053). Conclusion: This multicenter retrospective study revealed that Ruxolitinib is an effective treatment option for patients with cGVHD, with good ORR and CB. The achievement of CB in the first 3 months correlated well with steroid dose reduction. It suggests that Ruxolitinib is a feasible GVHD treatment option, even for patients who were heavily pretreated for cGVHD or failed previous TKI drug. Figure 1 Disclosures Hamad: Abbvie: Honoraria; Novartis: Honoraria. OffLabel Disclosure: Ruxolitinib treatment for steroid resistant chronic GVHD

Aortic Acceleration Time and the Intraoperative Assessment of Aortic Stenosis

Aortic acceleration time (AAT) and the ratio of AAT to ejection time (AAT/ET) are relatively new echocardiographic measures of the severity of aortic stenosis (AS). This study investigated the utility of transesophageal echocardiography (TEE) measurements of AAT and AAT/ET to predict the severity of AS under intraoperative conditions. Retrospective diagnostic accuracy study. St. Vincent's Hospital, Melbourne, Australia, from July 2007 to February 2017. The study comprised 199 patients who underwent aortic valve replacement (AVR) and whose aortic valves were evaluated with spectral Doppler analysis in both preoperative transthoracic echocardiography (TTE) and intraoperative TEE studies fewer than three months apart. Exclusion criteria included AVR for only aortic regurgitation, AVR of prosthetic aortic valves, and known left ventricular outflow tract obstruction. Standard echocardiography assessment of AS and the AAT and AAT/ET measurements was performed using preoperative TTE and intraoperative TEE. The intraoperative AAT and AAT/ET were increased significantly in patients with both high- and low-gradient severe AS compared with patients without severe AS (p < 0.01). Comparing preoperative TTE and intraoperative TEE measurements showed that the AAT was significantly prolonged during general anesthesia (mean difference 9.67 msec [95% confidence interval -13.54 to -5.81]), whereas the AAT/ET was preserved (mean difference -0.0018 [95% confidence interval -0.013 to 0.0091]). An intraoperative TEE cutoff of 109 msec for AAT and 0.35 for AAT/ET had a 74% and 67% sensitivity and 72% and 78% specificity, respectively, to differentiate severe from non-severe AS. The AAT and AAT/ET may be useful adjuncts for the intraoperative measurement of AS. The agreement between intraoperative TEE and preoperative TTE was better with AAT/ET compared with AAT alone.

Advanced natural language processing technique to predict patient disposition based on emergency triage notes.

To demonstrate the potential of machine learning and capability of natural language processing (NLP) to predict disposition of patients based on triage notes in the ED. A retrospective cohort of ED triage notes from St Vincent's Hospital (Melbourne) was used to develop a deep-learning algorithm that predicts patient disposition. Bidirectional Encoder Representations from Transformers, a recent language representation model developed by Google, was utilised for NLP. Eighty percent of the dataset was used for training the model and 20% was used to test the algorithm performance. Ktrain library, a wrapper for TensorFlow Keras, was employed to develop the model. The accuracy of the algorithm was 83% and the area under the curve was 0.88. Sensitivity, specificity, precision and F1-score of the algorithm were 72%, 86%, 56% and 63%, respectively. Machine learning and NLP can be together applied to the ED triage note to predict patient disposition with a high level of accuracy. The algorithm can potentially assist ED clinicians in early identification of patients requiring admission by mitigating the cognitive load, thus optimises resource allocation in EDs.

Rate Control Versus Rhythm Control in Patients with Left Ventricular Assist Devices and Atrial Fibrillation.

Atrial fibrillation (AF) is a common comorbidity in patients with left ventricular assist devices (LVAD) with no defined guideline treatment strategy of rate versus rhythm control. The purpose of this study is to determine the effects of rate versus rhythm control for AF on the outcomes of patients with LVAD at our institution. Consecutive patients who underwent LVAD implantation at St Vincent Hospital from January 1, 2015 to December 31, 2017 were retrospectively evaluated. Patients with AF were identified and divided into rate control or rhythm control groups. The primary outcome evaluated was a composite of death, heart failure admission, gastrointestinal bleed, ventricular tachycardia, cerebrovascular accident, hemolysis, and pump thrombosis. Secondary outcomes included the individual variables from the primary outcome. Out of 201 patients that underwent LVAD implantation, 81 had AF after implantation and were included with a median follow-up period of 384 days. The rate control group (n = 31; 38%) and the rhythm control group (n = 51; 62%) had no difference in composite outcomes (61% vs 59%, p = 0.83). When taken individually there was no difference in outcomes between the two groups. Thirteen patients underwent electrical cardioversion and successful conversion to normal sinus rhythm occurred in 71% of cases with a 60% recurrence rate. There was no difference in primary outcome between rate and rhythm control groups. These data suggest that maintenance of sinus rhythm may not be necessary in all patients with LVAD.

Supporting black lives 'mattering' with flexible health care.

Black lives 'mattering' should mean intrinsically supporting feasible healthcare options for Aboriginal and Torres Strait Islander people. This requires reimagining outmoded, 'neo-colonial' type models of care with implicit prejudice in hospital emergency departments (EDs). Equitably serving the needs of vulnerable cohorts like First Nations people that currently suffer most from lack of access to suitable healthcare is incumbent on government and society. To 'close the gap' for Aboriginal people, flexible treatment options should be designed with and for indigenous communities; developing models of care that will improve Aboriginal patient's attendance and completion of treatment in emergency departments. Flexiclinic, jointly developed by the Aboriginal Liaison Service and St Vincent's Hospital ED has developed such an innovative model. Since its recent inception, it has already shown enormous benefits, both in promoting equitable access and improving the health and welfare of Aboriginal patients who are receiving ongoing and quality care.