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Intravital imaging and microcomputed tomography revealed preserved PTC permeability and better terminal capillary density in caspase-3-/- mice. Collectively, these results demonstrate the pivotal importance of caspase-3 in regulating long-term renal function after IRI and establish the predominant role of PTC dysfunction as a major contributor to progressive renal dysfunction.NEW & NOTEWORTHY Our findings demonstrate the pivotal importance of caspase-3 in regulating renal microvascular dysfunction, fibrogenesis, and long-term renal impairment after acute kidney injury induced by ischemia-reperfusion injury. Ulixertinib in vivo Furthermore, this study establishes the predominant role of peritubular capillary integrity as a major contributor to progressive renal dysfunction after ischemia-reperfusion injury.The relevance of primary cilia shortening in kidney disease and its pathomechanism are largely unknown. Tubular damage in acute kidney injury (AKI) is strongly associated with mitochondrial dysfunction. Thus, we investigated the interaction between primary cilia and mitochondria in cisplatin-induced AKI mouse models. We observed that the expression of intraflagellar transport 88 (IFT88), a ciliary maintenance protein, was decreased in the renal cortex following tubular damage due to cisplatin-induced AKI. This result was consistent with the decreased IFT88 expression in cisplatin-treated RPTEC/TERT1 cells (human primary proximal tubular cells) parallel to the shortening of primary cilia, suggesting a causative link between tubular damage and IFT88-mediated cilia regulation. To address the effect of impaired primary cilia with decreased IFT88 expression on tubular function, RPTEC/TERT1 cells treated with cisplatin and knocked down for IFT88 using siRNA (IFT88-KD) were assessed for phenotypic changes and mitochy open new avenues for the development of novel therapeutic approaches in the treatment of acute kidney injury.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune orbital disease characterized by edema of extraocular muscles (EOMs).

To characterize the inflammation of EOMs in patients with TAO before and after radiation therapy using apparent diffusion coefficient (ADC) and to analyze the correlation between ADC and clinical activity of TAO.

The ADCs of superior rectus (SR), inferior rectus (IR), medial rectus (MR), and lateral rectus (LR) muscles were measured in 52 eyes of 26 patients with TAO before and three months after orbital radiation therapy. In addition, 38 eyes of 20 healthy volunteers were included. The clinical activity score (CAS) was evaluated. The ADC maps were reconstructed and measured on the coronal diffusion-weighted imaging (DWI) sequence and calculated in mm

/s.

The mean ADCs of EOMs before treatment were 1.42 ± 0.23 in SR, 1.37 ± 0.23 in IR, 1.41 ± 0.21 in MR, and 1.28 ± 0.25 in LR. The mean ADCs after treatment were 1.27 ± 0.18, 1.22 ± 0.26, 1.30 ± 0.22, and 1.15 ± 0.21, respectively. The ADCs were significantly decreased after treatment (all

 < 0.001). The ADCs of patients with TAO were significantly higher than those of controls. There was a statistically significant correlation between the mean ADCs and the CAS in each patient with TAO both before and after treatment (before r = 0.520;

 < 0.001; after r = 0.625;

 < 0.001).

The ADC values of EOMs can be exploited as a quantitative indicator to evaluate the clinical activity and monitor the therapeutic responses of patients with TAO.

The ADC values of EOMs can be exploited as a quantitative indicator to evaluate the clinical activity and monitor the therapeutic responses of patients with TAO.This brief report describes our experiences and the holiday service project that was safely conducted at the height of the COVID-19 resurgence in Michigan. As COVID-19 resurgence emerged in the United States and Europe, many establishments were forced to decrease their services and or cease functioning altogether. While other organizations faltered, our chapter found the means to continue to work during the pandemic.Epistaxis is commonly seen as an acute presentation to the emergency department. The level of severity can range from a minor ooze to a life-threatening bleed. The initial management is often the responsibility of junior doctors working in otolaryngology or the emergency department, so they must be familiar with the initial steps in treating this often distressing condition. The COVID-19 pandemic has complicated matters further as much of the management takes place in the upper airway. This article outlines the key considerations in the management of epistaxis, especially during the COVID-19 pandemic.Bronchiectasis is a common respiratory condition, characterised by abnormal bronchial dilatation, that often leads to recurrent airway infection and inflammation. It is an increasingly recognised respiratory condition, both as a primary lung disease but also co-existing with other respiratory diseases, such as chronic obstructive pulmonary disease and asthma. Diagnosis can have important treatment implications. There are shared systematic approaches to treatment, such as sputum clearance techniques, prompt treatment of exacerbations and, in certain circumstances, regular antibiotic therapy. It is vital to target antibiotic therapy appropriately, and knowledge of the patient's airway microbiology can assist with this. Certain infective and colonising organisms, such as Pseudomonas aeruginosa, cause worse patient outcomes and so need prompt treatment with appropriate antibiotics. In addition to this general management approach, there are many different underlying causes of bronchiectasis that should be identified wherever possible, to support more targeted therapy and prevent disease progression. This article provides a guide to the key principles of diagnosing and managing bronchiectasis, and outlines situations where more specialist respiratory support is required.Lunate dislocation is an uncommon but serious wrist injury, often resulting from a high energy mechanism of trauma. Advanced trauma life support protocols should be followed to diagnose and treat concomitant life-threatening pathology. Thorough neurovascular and soft tissue examination is required to identify open wounds and median nerve dysfunction, including acute onset carpal tunnel syndrome. Imaging is undertaken to appreciate injury severity, which is graded by the Mayfield classification. Closed reduction in the emergency department is the initial management, which alleviates pressure on neurovascular structures. Definitive management is surgical, most commonly via open reduction and direct ligamentous stabilisation. The aims of surgery are to restore anatomical carpal alignment and maintain stability, allowing repair and healing of the important wrist ligaments. Medium-to long-term functional outcomes are adequate, with most patients returning to work within 6 months. However, progressive radiographic midcarpal arthrosis is common, as well as permanent loss of grip strength, range of motion and chronic pain. This article considers the anatomy, diagnosis and management of acute lunate and perilunate dislocations.The NHS has always struggled to effectively adopt innovative medical technologies. A report by The Medical Technology Group argues that a new system for the widespread adoption of technology is needed. The report argues that, considering the growing backlog of procedures caused by the COVID-19 pandemic, medical technology can increase efficiency and deliver better outcomes for patients, while helping the NHS to recover.Interstitial lung diseases are a complex group of conditions that cause inflammation and scarring of the lung interstitium. This article discusses the diagnosis and management of common interstitial lung diseases including idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, connective tissue disease associated-interstitial lung disease, sarcoidosis and drug-induced interstitial lung disease. A multidisciplinary approach to diagnosis of interstitial lung disease is the gold standard; key history and examination features, blood panel, pulmonary function tests, high resolution computed tomography imaging, and when required bronchoalveolar lavage and lung biopsy results are discussed to reach a multidisciplinary consensus diagnosis. Advances, including the development of the disease-modifying anti-fibrotic medications nintedanib and pirfenidone, continue to shape the future management of interstitial lung disease. A holistic approach to the care of patients with interstitial lung disease is paramount, as they often have a high symptom burden and considerable palliative care needs.Lateral condyle fracture of the humerus is the second most common paediatric elbow fracture and is often missed, which can result in severe consequences including malunion, growth arrest and tardy ulnar nerve palsy. The difficulty in managing this fracture stems from a lack of awareness and the often subtle findings on radiographs. Patients can also present with quite vague symptoms; clinicians who do not have a high index of suspicion may not investigate beyond the initial clinical assessment and could miss vital cues. This article provides a guide to managing this common paediatric fracture, from initial presentation to definitive treatment, and discusses the complications that can ensue if managed incorrectly.Central venous catheters are sited for a variety of reasons in the adult critically ill patient. There is clear guidance for indications and maintenance of central venous catheters, but there is no clear guidance on how long a central venous catheter should remain in situ. This article looks at evidence to answer this question.People with severe and difficult to control asthma can be a complex and heterogenous group of patients often with multiple comorbidities. Living with this disease imposes a huge physical and psychological burden upon the patient which requires a comprehensive, systematic and patient-focused assessment, using a wide range of clinical expertise from within the multidisciplinary team. This article describes a severe asthma systematic and multidimensional day case assessment, and the positive benefits that the authors perceive it offers for patient care. These benefits include a confirmed diagnosis, consideration of alternative diagnosis, enhanced adherence, medication optimisation, access to and gatekeeping of high-cost specialist medications, improved patient self-management skills and signposting to appropriate therapies. As a consequence, they believe that this facilitates better patient outcomes through a reduction in corticosteroid exposure, exacerbations and hospitalisation. This severe asthma multidisciplinary team day case approach offers more than just physical benefits when compared with the traditional medical model. Patient feedback reports an excellent patient experience, feeling listened to, understood, empowered and hopeful for the future.Pulmonary embolism remains a common and potentially deadly disease, despite advances in diagnostic imaging, treatment and prevention. Managing pulmonary embolism requires a multifactorial approach involving risk stratification, determining appropriate diagnostics and selecting individualised therapy. This article reviews the pathophysiology, risk factors, clinical presentation, diagnostic evaluation and therapeutic management and early outpatient management of pulmonary embolism. The second part summarises pulmonary embolism in the setting of pregnancy, COVID-19, recurrent disease and chronic thromboembolic pulmonary hypertension.