Rejected

Primary biliary cholangitis (PBC) is a progressive, autoimmune, cholestatic liver disease affecting approximately 15 000 individuals in the UK. Updated guidelines for the management of PBC were published by The European Association for the Study of the Liver (EASL) in 2017. We report on the first national, pilot audit that assesses the quality of care and adherence to guidelines.

Increases in cat ownership worldwide mean more cats are requiring veterinary care. Illness, trauma and surgery can result in acute pain, and effective management of pain is required for optimal feline welfare (ie, physical health and mental wellbeing). Validated pain assessment tools are available and pain management plans for the individual patient should incorporate pharmacological and non-pharmacological therapy. Preventive and multimodal analgesia, including local anaesthesia, are important principles of pain management, and the choice of analgesic drugs should take into account the type, severity and duration of pain, presence of comorbidities and avoidance of adverse effects. Nursing care, environmental modifications and cat friendly handling are likewise pivotal to the pain management plan, as is a team approach, involving the cat carer.

Diabetic muscle infarction (DMI), which is also referred to as diabetic myonecrosis, is a rare and long-term complication of poorly controlled diabetes mellitus, while we found that acute diabetes decompensation, such as diabetic ketoacidosis (DKA), could also stimulate the occurrence and development of DMI.

Cat-scratch disease (CSD) is an infectious disease that usually presents with fever, headache, loss of appetite, weight loss, tender lymphadenopathy, and other symptoms. CSD is also the most common cause of infectious lymphadenitis in children, adolescents, and young adults. This contagious disease most often results from a scratch or bite of a cat. The course of this disease depends on the patient's immune status. CSD sometimes presents as a systemic disease and leads to various disease entities. In this study, we describe the case of a 23-year-old man exhibiting fever, generalized weakness, and neck swelling. The patient was unconscious when presented to the Emergency Department. He was given at least 3-4 liters IV bolus of 0.9% normal saline, but it failed to raise the blood pressure. He was then given an inotropic drug (noradrenaline) for low blood pressure and antibiotics (azithromycin) for fever. Venereal disease research laboratory (VDRL) and human immunodeficiency virus (HIV) serology came out negative. Histopathology ruled out tuberculosis and malignancy and confirmed necrotizing/suppurative granulomatous inflammation. These features favor the diagnosis of CSD.

The role of astrocytes in major depressive disorder has received great attention. Increasing evidence indicates that decreased astrocyte numbers in the hippocampus may be associated with depression, but the role of necroptosis in depression is unknown. Here, in a chronic unpredictable mild stress (CUMS) mouse model and a corticosterone (Cort)-induced human astrocyte injury model , we found that mice treated with chronic unpredictable mild stress for 3-5 weeks presented depressive-like behaviors and reduced body weight gain, accompanied by a reduction in astrocytes and a decrease in astrocytic brain-derived neurotropic factors (BDNF), by activation of necroptotic kinases, including RIPK1 (receptor-interacting protein kinase 1)/p-RIPK1, RIPK3 (receptor-interacting protein kinase 3)/p-RIPK3 and MLKL (mixed lineage kinase domain-like protein)/p-MLKL, and by upregulation of inflammatory cytokines in astrocytes of the mouse hippocampus. In contrast, necroptotic kinase inhibitors suppressed Cort-induced necroptotic kinase activation, reduced astrocytes, astrocytic necroptosis and dysfunction, and decreased Cort-mediated inflammatory cytokines in astrocytes. Treatment with fluoxetine (FLX) for 5 weeks improved chronic unpredictable mild stress-induced mouse depressive-like behaviors; simultaneously, fluoxetine inhibited depression-induced necroptotic kinase activation, reversed the reduction in astrocytes and astrocytic necroptosis and dysfunction, decreased inflammatory cytokines and upregulated brain-derived neurotropic factors and 5-HT1A levels. Furthermore, fluoxetine had no direct inhibitory effect on receptor-interacting protein kinase 1 phosphorylation. The combined administration of fluoxetine and necroptotic kinase inhibitors further reduced corticosterone-induced astrocyte injury. In conclusion, the reduction in astrocytes caused by depressive-like models and may be associated with the activation of necroptotic kinases and astrocytic necroptosis, and fluoxetine exerts an antidepressive effect by indirectly inhibiting receptor-interacting protein kinase 1-mediated astrocytic necroptosis.

To analyze and explore the clinical efficacy of ultrasound guided femoral nerve block combined with modified swelling anesthetic solution in high ligation and stripping of the great saphenous vein.

The syndrome of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare diagnosis that is often missed due to lack of both definitive diagnostic criteria and awareness of the disease. This case report describes a patient with chronic lymphocytic leukemia whose diagnosis of RS3PE was possibly delayed due to concomitant treatment-related arthralgias. The pathophysiology, presentation, and treatment of RS3PE are discussed. Greater awareness of malignancy-related RS3PE is crucial from a palliative care perspective as typical opioid pain management will prove ineffective and delay appropriate treatment.

Cyclovirobuxine D (CVB-D), the main active constituent of traditional Chinese medicine , was developed as a safe and effective cardiovascular drug in China. has also been used to relieve various pain symptoms for centuries. In this study, we examined and uncovered strong and persistent analgesic effects of cyclovirobuxine D against several mouse models of pain, including carrageenan- and CFA-induced inflammatory pain and paclitaxel-mediated neuropathic hypersensitivity. Cyclovirobuxine D shows comparable analgesic effects by intraplantar or intraperitoneal administration. Cyclovirobuxine D potently inhibits voltage-gated Ca2.2 and Ca3.2 channels but has negligible effects on a diverse group of nociceptive ion channels distributed in primary afferent neurons, including Na1.7, Na1.8, TRPV1, TPRA1, TRPM8, ASIC3, PX and PX. Moreover, inhibition of Ca3.2, rather than Ca2.2, plays a dominant role in attenuating the excitability of isolated dorsal root ganglion neurons and pain relieving effects of cyclovirobuxine D. Our work reveals that a currently in-use cardiovascular drug has strong analgesic effects mainly blockade of Ca3.2 and provides a compelling rationale and foundation for conducting clinical studies to repurpose cyclovirobuxine D in pain management.

Literature suggests an association between patent foramen ovale (PFO) and migraine, mostly migraine with aura (MA). Previous data suggest that air microembolism through PFO can lead to bioelectrical abnormalities detectable at electroencephalogram (EEG) in patients with MA, thus suggesting a pathophysiological mechanism for the MA-PFO association. However, those data lack replication.

To evaluate the association of tracheostomy timing with all-cause mortality in patients with mechanical ventilation (MV).