Evaluating Safety and Efficacy of Follow-up for Patients With Abdominal Pain Using Video Consultation (SAVED Study): Randomized Controlled Trial.

BACKGROUND: The benefits of telemedicine include cost savings and decentralized care. Video consultation is one form that enables early detection of deteriorating patients and promotion of self-efficacy in patients who are well but anxious. Abdominal pain is a common symptom presented by patients in emergency departments. These patients could benefit from video consultation, as it enables remote follow-up of patients who do not require admission and facilitates early discharge of patients from overcrowded hospitals. OBJECTIVE: The study aimed to evaluate the safety and efficacy of the use of digital telereview in patients presenting with undifferentiated acute abdominal pain. METHODS: The SAVED study was a prospective randomized controlled trial in which follow-up using existing telephone-based telereview (control) was compared with digital telereview (intervention). Patients with undifferentiated acute abdominal pain discharged from the emergency department observation ward were studied based on intention-to-treat. The control arm received routine, provider-scheduled telereview with missed reviews actively coordinated and rescheduled by emergency department staff. The intervention arm received access to a platform for digital telereview (asynchronous and synchronous format) that enabled patient-led appointment rescheduling. Patients were followed-up for 2 weeks for outcomes of service utilization, efficacy (compliance with their disposition plan), and safety (re-presentation for the same condition). RESULTS: A total of 70 patients participated, with patients randomly assigned to each arm (1:1 ratio). Patients were a mean age of 40.0 (SD 13.8; range 22-71) years, predominantly female (47/70, 67%), and predominantly of Chinese ethnicity (39/70, 56%). The telereview service was used by 32 patients in the control arm (32/35, 91%) and 18 patients in the intervention arm (18/35, 51%). Most patients in control (33/35, 94%; 95% CI 79.5%-99.0%) and intervention (34/35, 97%; 95% CI 83.4%-99.9%) arms were compliant with their final disposition. There was a low rate of re-presentation at 72 hours and 2 weeks for both control (72 hours: 2/35, 6%; 95% CI 1.0%-20.5%; 2 weeks: 2/35, 6%, 95% CI 1.0%-20.5%) and intervention (72 hours: 2/35, 6%; 95% CI 1.0%-20.5%; 2 weeks: 3/35, 9%, 95% CI 2.2%-24.2%) arms. There were no significant differences in safety (P>.99) and efficacy (P>.99) between the two groups. CONCLUSIONS: The application of digital telereview for the follow-up of patients with abdominal pain may be safe and effective. Future studies are needed to evaluate its cost-effectiveness and usefulness for broader clinical application. TRIAL REGISTRATION: ISRCTN Registry ISRCTN28468556; http://www.isrctn.com/ISRCTN28468556.

Gene silencing of receptor-interacting protein 2 protects against cigarette smoke-induced acute lung injury.

BACKGROUND AND PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by progressive alveolar damage and generally irreversible airflow limitation. Nuclear factor-κB (NF-κB) plays a critical role in COPD pathogenesis. Receptor-interacting protein 2 (Rip2), a 60 kDa adaptor protein, is a positive regulator of NF-κB pathway and also an inducible transcriptional product of NF-κB activation. We sought to investigate if Rip2 gene silencing could protect against cigarette smoke (CS)-induced acute lung injury. EXPERIMENTAL APPROACH: Gene silencing efficacy of Rip2 siRNA was characterized in mouse macrophage and mouse lung epithelial cell lines, and in a CS-induced acute lung injury mouse model. Bronchoalveolar lavage (BAL) fluid cell counts, levels of pro-inflammatory and oxidative damage markers, lung section inflammatory and epithelium thickness scorings, and nuclear NF-κB translocation were measured. KEY RESULTS: CS was found to upregulate Rip2 level in mouse lungs. Rip2 siRNA was able to suppress Rip2 levels in both macrophage and lung epithelial cell lines and in mouse lungs, block CS extract (CSE)-induced mediator release by the cultured cells, and abate neutrophil counts in BAL fluid from CS-challenged mice. Rip2 siRNA suppressed CS-induced inflammatory and oxidative damage markers, and nuclear p65 accumulation and transcriptional activation in lung tissues. Besides, Rip2 siRNA was able to disrupt CSE-induced NF-κB activation in a NF-κB reporter gene assay. CONCLUSIONS AND IMPLICATIONS: Taken together, we report for the first time that Rip2 gene silencing ameliorated CS-induced acute lung injury probably via disruption of the NF-κB activity, postulating that Rip2 may be a novel therapeutic target for COPD.

Oligonucleotide Therapy for Obstructive and Restrictive Respiratory Diseases.

Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology. Corticosteroids have been widely prescribed for the treatment of asthma, COPD, and IPF. However, the effectiveness of corticosteroids as an anti-inflammatory drug is limited by steroid resistance in severe asthma, the majority of COPD cases, and pulmonary fibrosis. There is an urgent medical need to develop target-specific drugs for the treatment of these respiratory conditions. Oligonucleotide therapies, including antisense oligonucleotide (ASO), small interfering RNA (siRNA), and microRNA (miRNA) are now being evaluated both pre-clinically and clinically as potential therapeutics. The mechanisms of action of ASO and siRNA are highly target mRNA specific, ultimately leading to target protein knockdown. miRNA has both biomarker and therapeutic values, and its knockdown by a miRNA antagonist (antagomir) has a broader but potentially more non-specific biological outcome. This review will compile the current findings of oligonucleotide therapeutic targets, verified in various respiratory disease models and in clinical trials, and evaluate different chemical modification approaches to improve the stability and potency of oligonucleotides for the treatment of respiratory diseases.

Collagen membranes for host-implant integration: a pilot clinical study.

PURPOSE: To evaluate host-implant integration with collagen membranes in 14 patients who underwent limb salvage surgery for musculoskeletal oncological disease. METHODS: 8 females and 6 males aged 10 to 69 (mean, 30) years underwent limb savage surgery with collagen membranes (Tutomesh; Tutogen Medical, Germany) for osteosarcoma (n=7), chondrosarcoma (n=3), giant cell tumour (n=1), malignant fibrous histiocytoma (n=1), arteriovenous malformation (n=1), and pigmented villonodular synovitis (n=1). The procedures performed were proximal humeral resection (n=3), partial scapulectomy (n=1), proximal femoral resection (n=2), total femoral resection (n=2), proximal tibial resection (n=3), and wide resection of soft tissues of the knee (n=3). In addition, 10 patients underwent endoprosthesis reconstruction. Reconstruction of musculoskeletal defects was classified into type I (intercalary, n=2), type II (joint, n=4), and type III (both, n=8). Graft incorporation and local recurrence were monitored. Clinical outcome measures entailed the Short Form-36, Toronto Extremity Salvage Score (TESS), and Musculoskeletal Tumor Society Score (MSTS). RESULTS: Two patients with proximal tibial resection and one with total femoral resection had wound healing problems. No patient had any infection or any foreign body reaction necessitating implant removal. Eight patients with type II or III reconstruction were followed up for a mean of 11 (range, 1-23) months. Their scores in the Short Form-36, TESS, and MSTS were similar to those who had undergone reconstructions without the membrane, with the exception of type II reconstructions for which the membrane conferred good results. CONCLUSION: The Tutomesh membrane facilitated host-implant integration and provided a feasible anatomic reconstruction for ligaments in the shoulder, knee, and hip.