Improving PD-1 blockade plus chemotherapy for complete remission of lung cancer by nanoPDLIM2.

Immune checkpoint inhibitors (ICIs) and their combination with other therapies such as chemotherapy, fail in most cancer patients. We previously identified the PDZ-LIM domain-containing protein 2 (PDLIM2) as a bona fide tumor suppressor that is repressed in lung cancer to drive cancer and its chemo and immunotherapy resistance, suggesting a new target for lung cancer therapy improvement. In this study, human clinical samples and data were used to investigate genetic and epigenetic changes in lung cancer.

Treatment with Oral or Inhaled Treprostinil in Patients with Pulmonary Arterial Hypertension and Cardiovascular Comorbidities.

Background: An increasing number of patients with pulmonary arterial hypertension (PAH) have cardiovascular comorbidities. However, the effects of comorbidities on responses to PAH treatment are not well understood.

Research Question: Do cardiovascular comorbidities in patients with PAH influence the efficacy and tolerability of inhaled or oral treprostinil?

Study Design And Methods: All patients from phase 3 studies TRIUMPH (N = 235) and FREEDOM-EV (N = 690) were included in this post hoc analysis and were classified as having 0, ≥1, or ≥2 cardiovascular comorbidities of interest based on patients' medical histories.

UKHCDO gene therapy taskforce: Guidance for implementation of haemophilia gene therapy into routine clinical practice for adults.

Introduction: 2022 was a landmark year with two adeno-associated viral vectors (AAVs) receiving conditional marketing authorization from EMA for the treatment of persons with severe haemophilia A and severe to moderately severe haemophilia B and a third in 2024. Gene therapy is a transformative, irreversible treatment with long-lasting effects, necessitating development of new clinical pathways to ensure optimal outcomes.

Aim: To develop a consensus framework and service specification for delivery of AAV gene therapy for haemophilia in adults within the UK using the hub-and-spoke model proposed by the European Association of Haemophilia and Allied Disorders and the European Haemophilia Consortium.

Pain Control after Otologic Surgery: Do Nonopioid Analgesics Suffice?

Objective: Investigate whether nonopioid analgesics (NOA) provide adequate pain control after otologic surgery.

Study Design: Retrospective multicenter cohort.

Setting: Two quaternary academic medical centers.

Ca and Nε-lysine acetylation regulate the CALR-ATG9A interaction in the lumen of the endoplasmic reticulum.

The acetylation of autophagy protein 9 A (ATG9A) in the lumen of the endoplasmic reticulum (ER) by ATase1 and ATase2 regulates the induction of reticulophagy. Analysis of the ER-specific ATG9A interactome identified calreticulin (CALR), an ER luminal Ca-binding chaperone, as key for ATG9A activity. Specifically, if acetylated, ATG9A is sequestered by CALR and prevented from engaging FAM134B and SEC62.