AZ Groeninge

Acute ischemic colitis associated with the use of neuroleptic agents is a rare but potentially life-threatening condition, and its true incidence is likely underestimated. The exact pathophysiological mechanisms underlying this complication remain poorly understood. Sigmoidoscopy or colonoscopy is considered the gold standard for diagnosis, although various imaging modalities can also aid in the diagnostic process. Preventive measures primarily involve the management of constipation and the reduction of risk factors. In cases of suspected neuroleptic-induced ischemic colitis, prompt adjustments in medication-either through dose reduction or substitution with alternative antipsychotics-should be considered. This article presents two cases of ischemic colitis caused by neuroleptic treatment, emphasizing the critical importance of early diagnosis and timely intervention.

BackgroundCentral retinal artery occlusion can result in permanent vision loss. Effective treatment is lacking.MethodsWe conducted a phase 3, double-blind, double-dummy, randomized, controlled trial involving adults with acute, nonarteritic central retinal artery occlusion who had symptom onset within 4.5 hours before treatment. Patients were assigned, in a 1:1 ratio, to receive intravenous tenecteplase (at a dose of 0.25 mg per kilogram of body weight) and oral placebo or intravenous placebo and oral aspirin (at a dose of 300 mg). The primary end point was vision recovery, defined as a best corrected visual acuity (BCVA) in the affected eye at 30 days of up to 0.7 logMAR (logarithm of the minimum angle of resolution; equivalent to ≥20/100). Key secondary visual end points were a BCVA of up to 0.5 logMAR (equivalent to ≥20/63), mean improvement in BCVA, and perimetry score at 30 days. Key safety end points included symptomatic intracranial hemorrhage, major bleeding, and death.ResultsA total of 78 patients at 16 sites in six countries underwent randomization, with 40 assigned to receive tenecteplase and 38 to receive aspirin. At 30 days, 8 patients (20%) in the tenecteplase group and 9 patients (24%) in the aspirin group had vision recovery (risk difference, −3.7 percentage points; 95% confidence interval, −22.0 to 14.7; P=0.69). The outcomes with regard to the secondary visual end points did not differ substantially between the groups. There was a greater incidence of adverse events in the tenecteplase group, including one fatal intracranial hemorrhage.ConclusionsIntravenous tenecteplase administered within 4.5 hours after onset of central retinal artery occlusion did not result in significantly greater vision recovery at 30 days than oral aspirin but was associated with serious safety concerns. (Funded by Oslo University Hospital and others; TenCRAOS ClinicalTrials.gov number, NCT04526951; EU Clinical Trials number, 2024-517606-29-00.)

BackgroundBlocking programmed cell death protein 1 (PD-1) has become a standard cancer immunotherapy, increasingly used in kidney, liver, or heart transplant recipients who develop skin cancer or hepatocellular carcinoma, despite the increased risk of graft failure or rejection. The mechanism of action of PD-1 blockade relies on stimulating CD8+ T cell activity, but its impact on humoral immunity in general and on alloimmunization in particular remains uncertain.ObjectiveThe aim of this study was to investigate the impact on anti-PD-1 treatment on alloimmunization.MethodsThe effect of anti-PD-1 treatment on the generation of anti-HLA (Human Leucocyte Antigen) antibodies was investigated in 72 patients with non-small cell lung cancer vaccinated with an allogeneic plasmacytoid dendritic cell line (PDC*line; six weekly injections), with or without pembrolizumab administered every three weeks. The kinetics and functionality of the anti-HLA generated were analyzed.ResultsThe results show that 51.4% of the patients developed anti-HLA antibodies, primarily dependent on the vaccine dose. In 60% of cases, the antibody response appeared after the sixth injection, peaked after one month, and then gradually declined over two years. Anti-HLA class II antibodies appeared earlier than class I antibodies. Functional assays demonstrated complement-dependent cytotoxicity against allogeneic B lymphocytes and PDC*line cells in the serum of some patients, with no difference related to treatment. PD-1 blockade did not alter the magnitude, kinetics, or cytotoxic potential of the vaccine-induced humoral response. ConclusionThese results indicate that, during allogeneic human vaccination, PD-1 signaling exerts a limited effect on antibody production and effector function, suggesting a more complex regulatory role in humoral immunity than previously thought.

Background: Somatostatin receptors (SSTRs), especially subtype 2 (SSTR2), are increasingly recognized as valuable molecular targets in the imaging of chronic inflammatory and immune-mediated diseases. Their expression on activated immune and stromal cells enables specific, non-invasive detection of inflammatory activity using radio-labeled somatostatin analogs. Objective: This review aims to summarize current evidence on SSTR-targeted imaging across a range of chronic inflammatory and immune-mediated diseases, compare its diagnostic value with 18F-FDG PET/CT, and discuss biological mechanisms, clinical applications, and remaining challenges. Methods: A literature-based narrative review was conducted, integrating preclinical studies, clinical trials, and comparative imaging research involving SSTR PET/SPECT tracers such as 68Ga-DOTATATE, 68Ga-DOTANOC, 99ᵐTc-HYNIC-TOC, and 111In-pentetreotide in diseases including vasculitis, sarcoidosis, autoimmune myocarditis, rheumatoid arthritis, and thyroid-associated ophthalmopathy. Results: SSTR-targeted imaging has shown promising specificity for inflammatory lesions and provides favorable lesion-to-background contrast, particularly in tissues with high physiological FDG uptake such as the myocardium and brain. In vasculitis and sarcoidosis, SSTR-targeted tracers may complement FDG PET by improving diagnostic confidence and inter-observer consistency in selected small studies. Mechanistically, SSTR2 expression is closely associated with cytokine-driven immune activation, predominantly involving M1 macrophages. However, current evidence remains limited by heterogeneous receptor expression, variable myocardial uptake, and the lack of standardized imaging protocols. Conclusions: SSTR-targeted molecular imaging represents a biologically grounded and clinically promising complementary approach for assessing immune-mediated inflammation. Future developments in tracer design, quantitative standardization, and multicenter clinical validation are warranted to establish its role in precision diagnostics.

BackgroundPatients with pancreatic ductal adenocarcinoma face a poor prognosis, with radical resection being the only potential cure. Because symptoms typically appear late, many patients are diagnosed with advanced disease. Locally advanced pancreatic tumours are characterised by extensive vascular involvement, which precludes R0 resection. Systemic therapy is therefore indicated, not only for palliation but also for reducing the risk of metastatic disease. Locoregional control remains paramount, irrespective of distant metastases as progressive tumours can cause considerable morbidity, negatively affecting patients’ quality of life. Previous studies investigating conventionally fractionated (chemo)radiotherapy have yielded mixed results, indicating opportunities for further research to optimise treatment outcomes. The TORPEDO study aims to prospectively assess whether adding stereotactic body radiation therapy (SBRT) to standard chemotherapy can improve outcomes in patients with initially inoperable, non-metastasized pancreatic ductal adenocarcinoma.MethodsThis study is a multicentre randomised phase II trial. While it primarily targets locally advanced lesions, patients with borderline resectable tumours who are either medically inoperable or decline surgery are also eligible. After twelve weeks of induction chemotherapy (modified FOLFIRINOX or gemcitabine/nab-paclitaxel), patients without development of distant metastases are randomised 1:1 to receive either continued chemotherapy alone (arm A) or one month of chemotherapy followed by SBRT (5 × 8 Gy) (arm B). Resectability is evaluated through a multidisciplinary tumour board. The primary endpoint is the 2-year progression-free survival. Secondary endpoints include overall survival, local progression-free survival, metastasis-free survival, objective response rate, resectability, R0 resection rates, surgical morbidity, toxicity, quality of life, and the impact of radiation doses on outcomes.DiscussionWe evaluate the efficacy and safety of SBRT following induction chemotherapy in patients with inoperable, non-metastasized pancreatic ductal adenocarcinoma. We hypothesize that adding SBRT enhances outcome by improving local control and increasing overall survival. Effective control of the pancreatic primary tumor may help reduce pain and thereby improve quality of life.Trial registrationThe ethics committee of the GZA Hospitals approved this study on April 8, 2024. It was registered on ClinicalTrials.gov (NCT06691425) on November 15, 2024.