Primary and secondary nonresponse to infliximab: mechanisms and countermeasures

Introduction: Primary and secondary non-response to infliximab are common in patients with inflammatory bowel disease and remain a management challenge in clinical practice.

Areas covered: This article describes the epidemiology, mechanisms and risk factors for primary and secondary nonresponse to infliximab in patients with inflammatory bowel disease. Data on proactive and reactive therapeutic drug monitoring are examined in this review. An algorithm for evaluation and management of non-response to infliximab is provided. Preventative measures are also discussed. Relevant articles were identified after a literature search using PubMed. Search terms included ‘infliximab’, ‘loss of response’, ‘immunogenicity’, and ‘drug monitoring’. References of identified articles were also reviewed to identify additional references.

Expert opinion: A common cause for primary and secondary non-response include inadequate dosing of infliximab; inadequate dosing can be identified through assessment of drug and anti-drug antibody levels. Therapeutic drug monitoring should be done in patients losing response to infliximab. Use of drug monitoring proactively is still under debate.     

Schwann cell-derived exosomes: Janus-faced mediators of regeneration and disease

The phenotypic plasticity of Schwann cells (SCs) has contributed to the regenerative potential of the peripheral nervous system (PNS), but also pathological processes. This double-sided effect has led to an increasing attention to the role of extracellular vesicles (EVs) or exosomes in SCs to examine the intercellular communication between SCs and their surroundings. Here, we first describe the current knowledge of SC and EV biology, which forms the basis for the updates on advances in SC-derived exosomes research. We seek to explore in-depth the exosome-mediated molecular mechanisms involved in the regulation of SCs and their microenvironment. This review concludes with potential applications of SC-derived exosomes as delivery vehicles for therapeutics and biomarkers. The goal of this review is to emphasize the crucial role of SC-derived exosomes in the functional integration of the PNS, highlighting an emerging area in which there is much to explore and re-explore.     

Therapeutic Advances in the Treatment of Holmes Tremor: Systematic Review

ObjectiveWe aimed to formulate a practical clinical treatment algorithm for Holmes tremor (HT) by reviewing currently published clinical data.Materials and MethodsWe performed a systematic review of articles discussing the management of HT published between January 1990 and December 2018. We examined data from 89 patients published across 58 studies detailing the effects of pharmacological or surgical interventions on HT severity. Clinical outcomes were measured by a continuous 1-10 ranked scale. The majority of studies addressing treatment response were case series or case reports. No randomized control studies were identified.ResultsOur review included 24 studies focusing on pharmacologic treatments of 25 HT patients and 34 studies focusing on the effect of deep brain stimulation (DBS) in 64 patients. In the medical intervention group, the most commonly used drugs were levetiracetam, trihexyphenidyl, and levodopa. In the surgically treated group, the thalamic ventralis intermedius nucleus (VIM) and globus pallidus internus (GPi) were the most common brain targets for neuromodulation. The two targets accounted for 57.8% and 32.8% of total cases, respectively. Overall, compared to the medically treated group, DBS provided greater tremor suppression (p = 0.025) and was more effective for the management of postural tremor in HT. Moreover, GPi DBS displayed greater benefit in the resting tremor component (p = 0.042) and overall tremor reduction (p = 0.022).ConclusionsThere is a highly variable response to different medical treatments in HT without randomized clinical trials available to dictate treatment decisions. A variety of medical and surgical treatment options can be considered for the management of HT. Collaborative research between different institutions and researchers are warranted and needed to improve our understanding of the pathophysiology and management of this condition. In this review, we propose a practical treatment algorithm for HT based on currently available evidence.     

Is neck tilt and shoulder imbalance the same phenomenon? A prospective analysis of 89 adolescent idiopathic scoliosis patients (Lenke type 1 and 2)

Purpose

To introduce a new clinical neck tilt grading and to investigate clinically and radiologically whether neck tilt and shoulder imbalance is the same phenomenon in AIS patients.

Methods

89 AIS Lenke 1 and 2 cases were assessed prospectively using the new clinical neck tilt grading. Shoulder imbalance and neck tilt were correlated with coracoid height difference (CHD), clavicle\rib intersection distance (CRID), clavicle angle (CA), radiographic shoulder height (RSH), T1 tilt and cervical axis.

Results

Mean age was 17.2 ± 3.8 years old. 66.3 % were Lenke type 1 and 33.7 % were type 2 curves. Strong intraobserver (0.79) and interobserver (0.75) agreement of the clinical neck tilt grading was noted. No significant correlation was observed between clinical neck tilt and shoulder imbalance (0.936). 56.3 % of grade 3 neck tilt, 50.0 % grade 2 neck tilt patients had grade 0 shoulder imbalance. In patients with grade 2 shoulder imbalance, 42.9 % had grade 0, 35.7 % grade 1, 14.3 % grade 2 and only 7.1 % had grade 3 neck tilt. CHD, CRID, CA and RSH correlated with shoulder imbalance. T1 tilt and cervical axis measurements correlated with neck tilt.

Conclusions

In conclusion, neck tilt is distinct from shoulder imbalance. Clinical neck tilt has poor correlation with clinical shoulder imbalance. Clinical neck tilt grading correlated with cervical axis and T1 tilt whereas clinical shoulder grading correlated with CHD, RSH CRID and CA.