Tubarial salivary glands on PSMA ligands based PET imaging and post 177Lu PSMA therapy scan: reiterating its importance

68Ga-PSMA PET/CT has been routinely utilized in patients with intermediate to high-risk category prostate carcinoma for staging, biochemical recurrence and before planning the PSMA radioligand therapy (RLT). 177Lu-PSMA RLT has also been approved by FDA as a novel treatment modality in metastatic carcinoma prostate patients who have failed to other lines of treatment. The non-target organs like salivary and lacrimal glands have shown to have high physiological PSMA uptake on PSMA PET/CT. Recently, strong uptake of PSMA ligand has also been noted in the dorsal wall of the nasopharynx in the region of torus tubarius on PSMA PET/CT, which has led to the identification of new pair of salivary gland structures called “tubarial salivary glands”. The clinical significance of these distinct anatomical structures lies in the fact these structures might be involved in a variety of immune related, inflammatory disorders, malignancies and could be a probable organ at risk during radiotherapy in case of head and neck malignancies, causing adverse effects to the patient

Acute-on-Chronic Liver Failure (ACLF): The ‘Kyoto Consensus’-Steps From Asia

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the APASL ACLF Research Consortium (AARC) was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the \u27Golden Therapeutic Window\u27, the \u27transplant window\u27, and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The \u27Kyoto APASL Consensus\u27 presented below carries the final recommendations along with the relevant background information and areas requiring future studies

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

TRANSFORMATION OF BUSINESS USING GAMIFICATION

Mike Joshi (MJ) - IT Director of ABC Corp (ABC) just got done with a meeting with Bob – Executive Vice President of Global Field Operations and Assurance for ABC Corp. MJ was asked to improve the output of ABC Corp’s current workforce to stay competitive in the hyper competitive telecommunications sector using technology. Bob demanded that MJ figure out a way to improve efficiency in ABC’s staff as they needed to push for the 5G deployment as well as Intelligent Edge Network. MJ was already aware of the fact that T-Mobile, one of ABC Corp’s fiercest competitors, was gaining traction on them on network connectivity, customer satisfaction and plethora of services it was providing. T-Mobile was offering incentives to ABC Corp’s existing customer to leave ABC Corp and move their service. 5G was in the midst of deployment and could become a game changer in terms of mobile connectivity and data throughput. It was a necessity in the world of social media, where the majority of the world population had handheld devices. Bob knew he needed skilled technology workers as well as customer care to support this mobile technology. How would he achieve such a goal when he was faced with a trimmed workforce? Bob wanted to know how he could squeeze higher performance from his top performers in the company using technology. Could he drive someone to put in the hard work required with the implementation of 5G and supporting existing technology and services? Bob needed a leaner and much more agile workforce especially after the recent job restructuring at ABC Corp. Bob needed employees to keep moving the goal line for the performance metric when T-Mobile was able to win over some contracts with large corporations due to the output and quality of its workforce. T-Mobile was able to offer a faster time for implementation of network services and Bob knew in order to improve efficiency at ABC Corp he needed a cultural transformation inside the workforce. MJ knew he did not have much time to come up with a presentable plan to management. Bob was wondering if IT can build and implement any solution to help with the cultural transformation he needed. Bob also had an idea that there was an efficiency problem with the ABC Corp’ task force, he knew he would need MJ to pull some reports and analyze them to make sure he could back up his gut instinct.</jats:p