Diabetic gastroparesis: Therapeutic options

Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient’s quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG

Best practices for detection, assessment and management of suspected immune-mediated liver injury caused by immune checkpoint inhibitors during drug development

Immune checkpoint inhibitors (ICIs) have shown significant efficacy in patients with various malignancies, however, they are associated with a wide range of immune-related toxicities affecting many organs, including the liver. Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) is a distinctive form of drug induced liver injury (DILI), that differs from most DILI types in presumed underlying mechanism, incidence, and response to therapeutic interventions. Despite increased awareness of ILICI and other immune-related adverse effects of ICIs reflected by recent guidelines for their management in post marketing clinical practice, there is lack of uniform best practices to address ILICI risk during drug development. As efforts to develop safer and more effective ICIs for additional indications grow, and as combination therapies including ICIs are increasingly investigated, there is a growing need for consistent practices for ILICI in drug development. This publication summarizes current best practices to optimize the monitoring, diagnosis, assessment, and management of suspected ILICI in clinical trials using ICI as a single agent and in combination with other ICIs or other oncological agents. It is one of several publications developed by the IQ DILI Initiative in collaboration with DILI experts from academia and regulatory agencies. Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, ILICI detection, approach to a suspected ILICI signal, causality assessment, hepatic discontinuation rules and additional medical treatment

Magnetic resonance imaging of penile paraffinoma: Case report

Penile paraffinoma is a well-known delayed complication of paraffin oil injection into the penis for penile girth augmentation but its MRI features have not been previously described. Case presentation: A 35-year-old Ukraine man presented with erectile dysfunction, voiding difficulty and an irregular, hard and painful penile mass that had progressively grown over the last year. He reported having received, seven years before, several penile injections of paraffin oil for penile girth augmentation. On physical examination, the mass was tender, poorly delimited, and involved the whole penile shaft and the cranial part of the scrotum. Preoperative MRI, performed to determine the extent of tissue to be removed and the possibilities of penile reconstruction, showed a newly-formed homogeneous tissue, compressing but not infiltrating Buck's fascia, iso-hypointense relative to muscle on T1-weighted sequences, and with a low signal intensity at T2-weighted sequences. On T1-weighted fat suppressed sequences, it did not enhance with contrast administration. MRI data were confirmed by surgical findings, as the newly-formed scar tissue did not infiltrate Buck's fascia. Pathology confirmed the diagnosis of penile paraffinoma. Conclusion: MRI seems to provide an adequate imaging of the histological events occurring after injection of paraffin oil in the subcutaneous tissues. Penile paraffinoma remains a clinical diagnosis, but MRI features may be helpful in planning an adequate surgical strategy and, in selected cases, establishing the differential diagnosis with other penile diseases, including cancer