Rejected

Bipolar disorders (BDs) are associated with significant risk of suicide. BD patients (age ≥18 years) admitted to the hospital were identified from the National Inpatient Sample dataset. Based on the secondary diagnosis of chronic pain disorder (CPD), patients were stratified into two groups (1) BD with CPD (BD + CPD) and (2) BD without CPD (BD – CPD). Groups were matched (1:1) for the type of BD and compared for baseline characteristics and suicidal ideation/attempt (SI/SA). Compared with BD – CPD, most patients in the BD + CPD group were older (mean age, 47.6 vs. 40.4 years), female (58.4% vs. 55.2%), and white (77.2% vs. 66.7%). After adjusting for covariates, compared with the BD – CPD group, the BD + CPD group had 21% more risk of SI/SA (odds ratio, 1.21, p < 0.001). CPD is independently associated with the increased risk of suicide among patients with BD. Thus, comorbid CPD among patients admitted for BD can be an essential risk factor for suicide.

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by inflammatory back pain and spinal ankylosis due to pathological new bone formation. Here, we identified CXCL12 as a critical contributor to pathological new bone formation through recruitment of osteogenic precursor cells (OPCs). CXCL12 was found highly expressed in the regions that would potentially develop pathological new bone. OPCs were recruited to the regions where CXCL12 was up-regulated. Inhibition of CXCL12/CXCR4 axis with AMD3100 or conditional knockout of CXCR4 attenuated OPCs migration and subsequent pathological new bone formation in animal models of AS. By contrast, a genetically engineered animal model with CXCL12 overexpression developed a joint ankylosis phenotype. Furthermore, Rac1 was found essential for OPCs migration and pathological new bone formation. These findings ravel the novel role of CXCL12 in AS and indicate a potential strategy for targeting the CXCL12/CXCR4-Rac1 axis to prevent progression of axial skeleton ankylosis.

Multi-centre randomized clinical trial.

Opioid misuse and addiction have become a national crisis. New pain management guidelines call for the use of multimodal analgesia to manage acute pain. In hospital settings, a clinical decision aid that emphasizes multimodal analgesia may improve nurses' use of this opioid-sparing strategy.

Recalcitrant complex regional pain syndrome (CRPS) type 1 is a devastating condition.

To report a severe bilateral frosted branch angiitis associated with acute onset of systemic dermatomyositis.

The aim of this study was to gain deeper knowledge about how people with chronic widespread pain (CWP) experience the co-creation of a health plan for sustainable physical activity, working in partnership with a physiotherapist, supported by a digital platform.

Glutamate, the main excitatory neurotransmitter in the central nervous system, plays an essential role in several cognitive activities such as memorizing and learning. Excessive glutamate release and disturbance of glutamate homeostasis participates in multiple neuronal pathologies including cerebral ischemia (inadequate blood supply), traumatic brain injury (e.g., from a fall or an accident), multiple sclerosis, epilepsy, migraine, fetal hypoxia, or Alzheimer's disease. Attenuating excitotoxicity by, for example, targeting glutamate receptors has proved to be beneficial in animal models but has largely failed in clinical trials because of toxic side effects. New therapeutic concepts have been explored to reduce the excitotoxic effect caused by the excessive glutamate release by using or stimulating glutamate-depleting enzymes in the bloodstream. These enzymes indirectly act upon the brain by depleting glutamate in the bloodstream, which is believed to siphon it out of the brain. Recent studies have shown that bioconjugate approaches applied to such enzymes exacerbate this therapeutic effect but raise additional questions for future research. This Perspective provides an overview of lessons learned by our group when exploring bioconjugate approaches for combatting glutamate excitotoxicity as an illustration of how research on therapeutic bioconjugates is evolving.

A man in his 70s with background vascular disease presented with 7 months of painful non-resolving lower leg ulcers with eschar and petechiae, left lower ear lobe ulceration and dusky inflammation of the right ear. He demonstrated good bilateral pedal pulses and no peripheral oedema. No lymphadenopathy was palpated.Biopsy suggested leucocytoclastic vasculitis on chronic stasis changes. Blood investigations showed elevated rheumatoid factor and mixed polyclonal IgG and monoclonal IgM cryoglobulins. He was diagnosed with mixed cryoglobulinaemia, and consequent conducted flow cytometry revealed CD5 +marginal zone lymphoma with elevated serum free light chains and kappa/lambda ratio.One-month following rituximab and chlorambucil therapy, the patient's pain had much improved, ear ulcers had healed and several leg ulcers had reduced in width and depth. The petechial eruption had also resolved.

A previous investigation regarding contralateral seventh cervical nerve transfer (CC7) revealed a novel and effective approach to improve arm function in patients with chronic spastic paralysis. The patients who underwent both CC7 and standard rehabilitation showed greater functional improvements and spasticity reductions than patients in the control group, who underwent rehabilitation only. Additional efforts are needed to maximize the benefits in patients and establishing a supporting nursing program is a promising method for achieving this goal.