The effect of delirium preventive measures on the occurrence of postoperative cognitive dysfunction in older adults undergoing cardiovascular surgery. The DelPOCD randomised controlled trial.

STUDY OBJECTIVE: This trial examines the effect of delirium preventive measures on the incidence of postoperative cognitive dysfunction in older adults. DESIGN: In a randomised approach, a delirium prevention and a standard care group were compared regarding manifestation of postoperative cognitive dysfunction at seven days, three and twelve months postoperatively (primary outcome). To correct for practice effects and age-depended cognitive decline, a control group of age-matched healthy subjects was included. SETTING: The trial was conducted at the University Medical Centre Hamburg between 2014 and 2018, data assessment took place in the Anaesthesia Outpatient Clinic and on the surgical ward. PATIENTS: A total of 609 patients ≥60 years scheduled for cardiovascular surgery were enrolled, allocated treatment was received by 284 patients in the delirium prevention and 274 patients in the standard care group. INTERVENTION: The intervention consisted of a delirium prevention bundle including reorientation measures, sleeping aids and early mobilisation. MEASUREMENTS: Cognitive functions were assessed via neuropsychological testing of attention, executive functions including word fluency, and verbal memory utilizing a computerised test of attentional performance, the trail making test, the digit span subtest from the Wechsler Adult Intelligence Scale-IV, the verbal learning and memory test, and the Regensburg Word Fluency Test. Assessments were performed preoperatively and at three time points postoperatively (one week, three months and 12 months). MAIN RESULTS: Postoperative cognitive dysfunction was defined as a clinically meaningful decline in at least two out of nine chosen test parameters compared to the preoperative level (reliable change index ≤ - 1.96). The rates of postoperative cognitive dysfunction were 25.9% (delirium prevention group, n = 284) vs. 28.1% (standard care group, n = 274) [X2(1,n = 433) = 0.245;p = 0.621] at postoperative day seven and declined to 7.8% vs. 6.8% [X2(1,n = 219) = 0.081;p = 0.775] and 1.3% vs. 5.6% (p = 0.215, Fisher's exact test) at three and 12 months following surgery, respectively. The postoperative delirium rates did not differ between the two groups (delirium prevention group: 13.4% vs. standard care group: 17.3%). Attentional performance was impaired shortly after surgery, whereas verbal delayed recall was most frequently affected over the whole postoperative period. CONCLUSION: These findings suggest that an intervention combining specific measures extracted from established postoperative delirium prevention programs did not reduce the rate of postoperative cognitive dysfunction in older adults.

Soluble interleukin-2 receptors inhibit interleukin 2-dependent proliferation and cytotoxicity: explanation for diminished natural killer cell activity in cutaneous T-cell lymphomas in vivo?

In patients with cutaneous T-cell lymphomas (CTCL), soluble interleukin-2 receptor serum levels (sIL-2R) were determined by ELISA technique, and natural killer cell (NK) activity, by a 4-h chromium-51 release assay. Decrease of NK activity correlated with the augmentation of serum sIL-2R. After a 4-d stimulation with interleukin 2 CTCL patients' peripheral mononuclear cells (PMC) showed an increase of cytotoxic activity similar to that in healthy donors' PMC. Normal donors' PMC demonstrated a diminished IL-2-induced cytotoxic activity in 25% CTCL serum (sIL-2R of 3000, 7330, and 10700 U/ml, respectively) compared to control serum (sIL-2R of 400, 340, and 420 U/ml, respectively). IL-2-dependent proliferation of 2-d phytohemagglutinin (PHA) blasts was lower in CTCL serum than in control serum. sIL-2R was enriched from one CTCL patient's serum by IL-2 affinity chromatography. Transfection of the Tac gene into NIH/3T3 fibroblasts resulted in the production of a recombinant sIL-2R. The presence of enriched native or recombinant sIL-2R inhibited interleukin-2-dependent generation of cytotoxic activity and PHA blast proliferation. We suggest that elevated sIL-2R levels account for diminished NK activity by neutralizing interleukin 2 in CTCL patients.

Formation of neutralizing antibodies against natural interferon-beta, but not against recombinant interferon-gamma during adjuvant therapy for high-risk malignant melanoma patients.

In an adjuvant clinical trial, 34 high-risk malignant melanoma patients were treated with natural interferon (IFN)-beta and recombinant IFN-gamma. Patients with tumor location on head, neck, and trunk received 3 million IU IFN-beta intravenously (IV) three times weekly for 24 weeks. Patients with tumor location on the extremities received subcutaneous (SC) injection of 2 million IU of IFN-beta distal the locoregional lymph nodes instead. All patients were given 50 micrograms IFN-gamma SC on 3 consecutive days every 4 weeks. Antibody formation was detected by coincubation of IFN and patients' serum and assessment of the inhibition of the cytopathic effect by a virus suspension. Soluble interleukin-2 receptors (sIL-2R) were determined by enzyme-linked immunosorbent assay (ELISA) technique. No antibodies against IFN-gamma were observed. The overall incidence of antibody formation to IFN-beta was 55.8% (19/34). Ninety-two percent of the SC-treated patients (13/14) and 30% (six of 20) of the IV-treated patients developed antibodies. Soluble interleukin-2 receptors were found to be significantly lower in antibody-positive patients than in antibody-negative patients. The authors conclude that IFN-beta antibody formation is frequent and might influence IFN induced sIL-2R elevation in vivo.