Canakinumab: Promises and Future in Cardiometabolic Diseases and Malignancy

Inflammation has proven in multiple studies to be responsible for the progression of cardiometabolic diseases and malignancies. The interleukin family has been critically associated with progression of atherosclerosis, insulin resistance, and various malignancies. Given the advent of pharmacologic interleukin-1 (IL-1) inhibition, this pathway can potentially be targeted to improve outcomes. In the recently concluded Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial, investigators looked at the potential role of IL-1 (especially IL-1β) inhibition in halting the progression of atherosclerosis. In the subset analysis of the data from this trial, IL-1β inhibition with canakinumab was found to have beneficial effects in other cardiometabolic diseases characterized by inflammation, like diabetes, stroke, and chronic kidney disease, and also in patients with lung cancer. In this article, we will try to review the current literature on the role of canakinumab in the treatment of cardiometabolic diseases and malignancies.     

Diabetes Mellitus and Heart Failure: A Consensus Statement

International Journal of Diabetes in Developing Countries -     

Transperineal ultrasonography in perianal Crohn disease: A valuable imaging modality

Aims of treatment for Crohn disease have moved beyond the resolution of clinical symptoms to objective end points including endoscopic and radiological normality. Regular re-evaluation of disease status to safely, readily and reliably detect the presence of inflammation and complications is paramount. Improvements in sonographic technology over recent years have facilitated a growing enthusiasm among radiologists and gastroenterologists in the use of ultrasound for the assessment of inflammatory bowel disease. Transabdominal intestinal ultrasound is accurate, affordable and safe for the assessment of lumi-nal inflammation and complications in Crohn disease, and can be performed with or without the use of intravenous contrast enhancement. Perianal fistulizing disease is a common, complex and often treatment-refractory complication of Crohn disease, which requires regular radiological monitoring. Endoanal ultrasound is invasive, uncomfortable and yields limited assessment of the perineal region. Although magnetic resonance imaging of the pelvis is established, timely access may be a problem. Transperineal ultrasound has been described in small studies, and is an accurate, painless and cost-effective method for documenting perianal fluid collections, fistulas and sinus tracts. In the present article, the authors review the literature regarding perineal ultrasound for the assessment of perianal Crohn disease and use case examples to illustrate its clinical utility.     

Increasing economic burden of tyrosine kinase inhibitor treatment failure by line of therapy in chronic myeloid leukemia

Objective:

To assess the economic burden of tyrosine kinase inhibitor (TKI) treatment failure in chronic myeloid leukemia (CML), by assessing all-cause health care resource use (HCRU) and costs in the year after treatment failure by line of therapy (LOT; 1L/2L/3L) using real-world data.

Methods:

Treatment episodes initiating a TKI of interest (index TKI) during June 2008–December 2011 were identified from the IMS PharMetrics Plus Health Plan Claims Database for adult patients with CML diagnosis (ICD-9-CM 205.1x), 120 days pre-index continuous enrollment (CE) and no clinical trial participation. Episodes experiencing treatment failure, defined as switch to a non-index TKI or discontinuation of index TKI (gap of?≥?60 days), and with 1 year CE post-failure, were analyzed. LOT was determined by number of unique TKIs used in the pre-index. All-cause HCRU and costs (2012 USD) in the 1 year post-failure were assessed by LOT, and the comparisons between 1L and 2L failures were also adjusted using multivariate generalized linear models (GLMs) to control for underlying differences.

Results:

A total of 706 episodes were identified (518 1L; 180 2L; 8 3L). Unadjusted HCRU over 1 year post-failure increased significantly. This was accompanied by a significant increase in unadjusted mean costs for 2L failures vs. 1L failures ($99,624 vs. $78,667, p?=?0.021, Δ$20,957). Following the adjustment using GLMs, adjusted mean costs were 38% higher (95% CI 1.14–1.68), driven primarily by use of medical services. In adjusted analyses, compared to 1L, 2L failures had: 45% more ambulatory visits (mean 31 vs. 21, 95% CI 1.26–1.66), 75% higher risk of hospitalization (33% vs. 23% hospitalized, 95% CI 1.16–2.64), and 73% higher medical costs (95% CI 1.31–2.29). Medical costs comprised a greater proportion of total costs in 2L vs. 1L (55% vs. 44%); pharmacy costs did not increase significantly.

Conclusions:

The economic burden over 1 year post TKI failure increased with each sequential line of TKI treatment failure.     

Guillain–Barre syndrome: demographics,clinical features,and outcome in a single tertiary care hospital,Oman

Objectives:Guillain–Barre syndrome (GBS) is an acute autoimmune-mediated peripheral nervous system disease. Different studies from various geographical regions have reported considerable variability regarding its epidemiology, clinical features, and outcome. Our study aimed to document demographics, clinical features, and outcomes among GBS patients admitted to a single tertiary care hospital in Muscat, Oman.Methods:A retrospective data analysis of 44 GBS patients, who were admitted during a two-year period from January 2016 to December 2018 at Khoula hospital, was carried out. Demographics, antecedent illness, duration of symptoms, muscle power graded by the Medical Research Council scale (MRCs), sensory & autonomic involvements, nerve conduction study results, CSF study, need for ventilation, condition at discharge and subsequent follow-up status were obtained.Results:Ninety-one percent of the patients were Omanis, with male predominant 63.6% and the average age was 42.69 years. Quadriparesis was the predominant presenting complaint (61.3%) and AIDP was the commonest variant (52%). All patients received a single cycle of IVIg and (13.6%) patients admitted to the ICU for mechanical ventilation. The study showed good outcome and recovery in 18 months follow up.Conclusion:The clinical presentation of GBS in the majority of patients in Oman is similar to those reported in previous studies, and most patients had favorable prognoses. Our results can be used as baseline data for understanding the characteristics of GBS in Oman and, consequently, for better management.

Guillain–Barre syndrome (GBS), also known as Landry’s paralysis, is an acute immune-mediated polyradiculoneuropathy;1,2,3 with males are about 1.5 times more affected than females, and an overall incidence rate of 1–2 per 100,000 population per year worldwide.4,5 The syndrome is characterized by an acute or subacute progressive generalized muscle weakness of upper and lower limbs with relative or complete areflexia, and limb paraesthesia.1 The typical pattern starts with typically ascending flaccid paralysis, which progresses over a few days to a few weeks. Patients may also develop cranial nerves involvement, usually as a facial or pharyngeal weakness. In addition, autonomic dysfunction is common in the disease, which manifests as postural hypotension, loss of vasomotor control (causing wide fluctuation in blood pressure), and a variety of cardiac arrhythmias. Ventilator assistance is required when respiratory failure and oropharyngeal weakness develop in the course of the disease, which has been reported to be required in approximately one-third of hospitalized patients; these data indicate that early management is vitally important for GBS.1,3Proceeding infections (such as infections with Campylobacter jejuni, Cytomegalovirus, Epstein–Barr virus, Mycoplasma pneumonia, and HIV)2,4,5,6,7 may activate the immune response, owing to molecular mimicry, to cross-react with the peripheral nerve’s components (the myelin and/or the axon) resulting in the endoneural inflammation of spinal nerve roots, nerve’s distal segments, and at potential nerve entrapments sites.2 Some triggering factors (e.g., immunization, trauma, bone marrow transplantation, and surgery) may also affect the pathogenesis of GBS .6–8Seasonal variability is reported for GBS, which can reflect seasonal changes in the peaks of the predisposing factors, such as infections, although GBS may occur during any season.9,10 Seasonal occurrence has been reported to peak during the summer season in Asian countries.11,12The GBS is believed to include a variety of acute neuropathies with underlying immune-mediated pathogenic mechanisms rather than a single disease; therefore, GBS recognized variants are considered as syndromes [including acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor-sensory axonal neuropathy (AMSAN), and Miller–Fisher syndrome]. The most prevalent form of GBS reported is AIDP which is responsible for 70–90% of cases.5,6 In addition to history and clinical examination, confirming the diagnosis of GBS may include cerebrospinal fluid (CSF) analysis and electroneurodiagnostic testing, both of which can be normal in the early phase of the disease.3,4Therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) are used effectively for adult and pediatric patients with GBS; and if these treatments are administered during the first few weeks of the disease along with a efficient supportive care, they can minimize mortality and improve the outcome of the disease.13,14 Physical therapy is considered as an essential part of the supportive management for decreasing complications’ incidence, such as respiratory complications and deep venous thrombosis (DVT), as well as for pain management and to enhance early mobilization.15The understanding of clinical presentation and epidemiology of GBS in each population can help us better understand the pathogenesis of the disease, its risk factors, and prognosis.16 Moreover, the evaluation of GBS outcome may be effective for planning an appropriate therapeutic strategy and for determining disease-related morbidity and mortality. The results of different studies from various geographical regions have reported considerable variability regarding the epidemiology, clinical features, and outcomes of GBS.17,18 Therefore, our study aims to assess the presentation, clinical findings, demographics, seasonal variations, and outcomes among patients with GBS in a tertiary care institute in Muscat, Oman.