Rejected

T cells are established contributors to the pathogenesis of atopic dermatitis (AD) and psoriasis, yet whether they are the key drivers or simply unwitting participants remains incompletely understood. Conversely, malignant T cells are the undisputed culprits of cutaneous T cell lymphoma (CTCL), a group of diseases that share key clinical, histopathological and molecular features with inflammatory skin disease (ISD). Here, we compare the pathogenesis of ISD and CTCL and discuss the resulting insights. Recurrent, skin-limited disease implicates skin-resident T cells (T) in both ISD and CTCL. In CTCL, malignant T cells recruit benign T cells into inflammatory skin lesions, a disease-amplifying function also proposed for pathogenic T cells in ISD. Mechanistically, cytokines produced by malignant T cells in CTCL and by pathogenic T cells in ISD, respectively, are likely both necessary and sufficient to drive skin inflammation and pruritus, which in turn promotes skin barrier dysfunction and dysbiosis. Therapies for ISD target T cell effector functions but do not address the chronicity of disease while treatments for CTCL target malignant T cells but not primarily the symptoms of the disease. By integrating our understanding of ISD and CTCL, important insights into pathogenesis and therapy can be made which may improve the lives of sufferers of both disease groups.

Recent years have seen major advances in our understanding of primary biliary cholangitis, with the condition now renamed to reflect the majority of patients who do not have cirrhosis. Data from large multicentre studies have greatly increased our knowledge of the natural history of primary biliary cholangitis, making the identification of higher risk patients clearer and facilitating the development of new medications. Recent guidelines have emphasised the importance of risk stratification, targeted treatment of symptoms and early prioritisation for second line therapies. The review summarises recent major developments in our understanding of primary biliary cholangitis and its management.

To identify pediatric patient-reported outcomes (PROs) that are associated with chronic conditions and to evaluate the effects of chronic disease activity on PROs.

Incontinence-associated dermatitis is a common, under-recognized painful skin condition associated with poorer quality of life, increased nurse workloads, and costs.

To assess the narcotic use of older patients after oncologic resection.

Evidence about substance use and misuse among adults with disabilities is still emerging, despite increased risk of chronic pain and mental health problems, which are in turn risk factors for substance use and misuse.

Pancreatic-portal vein fistula, portal vein thrombosis and liver abscesses are rare complications of acute pancreatitis which occur in the setting of localised inflammation of the pancreatic tissues and surrounding structures. We discuss a 34-year-old woman with a medical history of intermittently controlled HIV and alcohol use disorder who presents with severe epigastric pain diagnosed with acute pancreatitis. Concerning CT findings showing hypoattenuating liver lesions likely to be abscesses and multiple pancreatic pseudocysts led us to order an MRI which showed thrombosis of the portal vein, porto-pancreatic pseudocyst fistulation and cirrhotic changes. Patient was treated conservatively in the hospital and ultimately given a course of antibiotics for hepatic abscesses. Workup for new diagnosis of cirrhosis revealed positive antimitochondrial antibodies, raising suspicion for autoimmune hepatitis possibly triggered by immune reconstitution in the setting of HIV infection. Patient was discharged on oral antibiotic therapy and home antiretroviral therapy.

Saporin is a ribosome-inactivating protein that can cause inhibition of protein synthesis and causes cell death when delivered inside a cell. Development of commercial Saporin results in a technology termed 'molecular surgery', with Saporin as the scalpel. Its low toxicity (it has no efficient method of cell entry) and sturdy structure make Saporin a safe and simple molecule for many purposes. The most popular applications use experimental molecules that deliver Saporin via an add-on targeting molecule. These add-ons come in several forms: peptides, protein ligands, antibodies, even DNA fragments that mimic cell-binding ligands. Cells that do not express the targeted cell surface marker will not be affected. This review will highlight some newer efforts and discuss significant and unexpected impacts on science that molecular surgery has yielded over the last almost four decades. There are remarkable changes in fields such as the Neurosciences with models for Alzheimer's Disease and epilepsy, and game-changing effects in the study of pain and itch. Many other uses are also discussed to record the wide-reaching impact of Saporin in research and drug development.

We present a case of piriformis syndrome in a woman in her 30's following low energy trauma, presenting with unilateral lower limb weakness, altered sensation and urinary retention. CT imaging revealed a bulky piriformis muscle which was further clarified on MRI as an intramuscular haematoma within the left piriformis causing compression of the left lumbosacral plexus. Haematoma formation was exacerbated due to use of an antiplatelet medication the patient was taking for Moyamoya disease, which carries an increased risk of cerebrovascular accident. Surgical exploration of the piriformis and sciatic nerve was undertaken and confirmed a haematoma within the piriformis. A full release of the piriformis tendon was undertaken, and the sciatic nerve was inspected, no further abnormality was found. After review in clinic post-discharge, the patient reported normal sensation and normal muscle power in her feet.

The impact of tramadol analgesic use before breast cancer diagnosis on survival in patients with chronic pain is unclear. Therefore, we designed a propensity score-matched population-based cohort study to compare the breast cancer-related survival of patients with chronic pain who received long-term tramadol analgesic treatment with that of those who did not receive such treatment.