Rejected

A 33-year-old male presenting with subacute abdominal pain was found to have hyperbilirubinaemia, hypokalaemia and hyponatraemia. This was in the setting of transitioning between deferasirox iron chelator formulations, from dispersible tablets to film-coated tablets for ongoing treatment of chronic iron overload secondary to transfusion requirement for beta-thalassemia major. A liver biopsy demonstrated acute cholestasis with patchy confluent hepatocellular necrosis and mild to moderate microvesicular steatosis. Based on the histological, biochemical and clinical findings, the diagnosis of hepatotoxicity and Fanconi-like syndrome was made. The patient improved clinically and biochemically with cessation of the deferasirox film-coated tablets and supportive management. To our knowledge, this is the first case report of hepatotoxicity and Fanconi-like syndrome occurring due to deferasirox film-coated tablets with previous tolerance of dispersible deferasirox tablets. It is important to raise clinical awareness of this potentially severe complication.

Chronic cough can be a troublesome clinical problem. Current thinking is that increased activity and/or enhanced sensitivity of the peripheral and central neural pathways mediates chronic cough processes similar to those associated with the development of chronic pain. While inflammation is widely thought to be involved in the development of chronic cough, the true mechanisms causing altered neural activity and sensitisation remain largely unknown. In this back-to-basic perspective article we explore evidence that inflammation in chronic cough may, at least in part, involve neuroinflammation orchestrated by glial cells of the nervous system. We summarise the extensive evidence for the role of both peripheral and central glial cells in chronic pain and hypothesise that the commonalities between the pain and cough pathogenesis and clinical presentation warrant investigations into the neuroinflammatory mechanisms that contribute to chronic cough. We open the debate that glial cells may represent an underappreciated therapeutic target for controlling troublesome cough in disease.

Iatrogenic nerve injuries are rare complications of total hip and knee arthroplasty, which may cause chronic pain and loss of function, severely affecting the patient's daily activities and quality of life. Nerves "at risk" include the sciatic nerve, the femoral nerve, the lateral femoral cutaneous nerve and the superior gluteal nerve during total hip arthroplasty, and the infrapatellar branch of the saphenous nerve as well as the peroneal nerve during total knee arthroplasty. Multiple procedure-related and patient-related factors have been identified to modify the risk of nerve injury in the course of lower limb joint replacement surgery. These include the surgeon's skills, the surgical approach, the type of implant fixation, the intraoperative positioning of the patient, as well as pre-existing scars, the patient's sex, age and comorbidities. Diagnostic and therapeutic approaches should be based on the aetiology of the lesion: iatrogenic nerve lesions can result from direct (compression or transection) and/or indirect (traction, ischemia) trauma. The majority of nerve injuries encountered in hip or knee arthroplasty has been referred to as "minor" nerve lesions, which generally respond very well to non-operative treatment. "Major" nerve lesions, such as complete motor nerve transection, may result in lifelong impairment. Any perioperatively encountered neurological deficit requires a meticulous diagnostic work-up and an individually tailored treatment strategy, respecting aetiology and anatomic site of the nerve lesion as well as the individual patient's needs and comorbidities.

A 73-year-old female with past medical history of essential hypertension, hyperlipidemia, seasonal allergies, and chronic back pain presented to the hospital with complaints of headaches, fevers, fatigue, generalized body aches, shortness of breath, and diarrhea. Initial complete blood count was remarkable for leukopenia with an absolute lymph count of 0.60 K/µL and severe thrombocytopenia (platelet count < 3 K/µL). She was tested for COVID-19 via nasopharyngeal swab polymerase chain reaction (PCR) testing and found positive. Additional labs showed an elevated D-dimer, C-reactive protein, fibrinogen, and lactate dehydrogenase. Vitamin B12 and folate levels were obtained and found to be normal. Peripheral smear showed no schistocytes or additional hematologic abnormalities apart from thrombocytopenia. The patient was transfused one unit of platelets with no improvement in platelet count. Fibrinogen count was obtained and found in normal range at 458 mg/dL. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) were all found to be normal. Immune thrombocytopenia purpura (ITP) was suspected and intravenous immunoglobulin (IVIG) was administered at a dose of 1 g/kg/day for two doses. By day 4, the patient had marked response to treatment with platelet recovery to 105 K/µL and subsequently discharged by day 5 with complete resolution of symptoms and platelet count of 146 K/µL. Twenty-eight days after discharge, she presented to hematology clinic with platelet count of 8 K/µL. Repeat nasopharyngeal swab PCR COVID testing was negative and she was treated with IVIG and pulse dexamethasone with prompt response, confirming suspicion of underlying, undiagnosed ITP prior to COVID infection.

Prior research studies on the association of obstructive sleep apnea (OSA) and pain intensity have examined older patients, there is a need to understand the relationship between OSA and pain intensity among younger adults.

Administration of NSAIDs for acute post-traumatic analgesia is increasing in popularity as an alternative to opioids despite reservations regarding its potential impact on the development of acute kidney injury (AKI). We hypothesized that early NSAID administration for analgesia would be associated with worsened renal function in severely injured trauma patients.

ATP and its ultimate degradation product adenosine are potent extracellular signalling molecules that elicit a variety of pathophysiological functions in the kidney through the activation of P2 and P1 purinergic receptors, respectively. Extracellular purines can modulate immune responses, balancing inflammatory processes and immunosuppression; indeed, alterations in extracellular nucleotide and adenosine signalling determine outcomes of inflammation and healing processes. The functional activities of ectonucleotidases such as CD39 and CD73, which hydrolyse pro-inflammatory ATP to generate immunosuppressive adenosine, are therefore pivotal in acute inflammation. Protracted inflammation may result in aberrant adenosinergic signalling, which serves to sustain inflammasome activation and worsen fibrotic reactions. Alterations in the expression of ectonucleotidases on various immune cells, such as regulatory T cells and macrophages, as well as components of the renal vasculature, control purinergic receptor-mediated effects on target tissues within the kidney. The role of CD39 as a rheostat that can have an impact on purinergic signalling in both acute and chronic inflammation is increasingly supported by the literature, as detailed in this Review. Better understanding of these purinergic processes and development of novel drugs targeting these pathways could lead to effective therapies for the management of acute and chronic kidney disease.

Peyronie's disease (PD), a fibrotic disorder of the tunica albuginea fully described in 1793 by French physician Francois de la Peyronie, is characterized by pain, plaque formation, penile deformity, and ultimately sexual function decline. The epidemiological data on PD vary considerably across previous studies, with recent evidence reporting a prevalence of up to 9%. PD is generally divided into two different phases: active or acute and stable or chronic. Plaque formation generally occurs during the acute phase, while during chronic phase pain usually tends to complete resolution and penile deformity stabilizes. PD's pathophysiology is still subject of great discussion. Tunical mechanical stress and microvascular trauma are major contributory factors. However, better understanding of the molecular pathophysiology of this condition remains paramount towards an in-depth comprehension of the disorder and the development of newer and more effective disease-targeted interventions. In this review we provide a detailed overview of natural history of PD, specifically focusing on clinical manifestations and the underlying molecular regulation patterns.