Macrophage-based cancer immunotherapy: Challenges and opportunities.

Macrophages play crucial roles in the tumor microenvironment (TME), exerting diverse functions ranging from promoting tumor growth and metastasis to orchestrating anti-tumor immune responses. Their plasticity allows them to adopt distinct activation states, often called M1-like (pro-inflammatory) and M2-like (anti-inflammatory or pro-tumoral), significantly influencing tumor progression and response to therapy. Harnessing the potential of macrophages in cancer immunotherapy has emerged as a promising strategy, with increasing interest in targeting these cells directly or modulating their functions within the TME. This review explores the intricate interplay between macrophages, the TME, and immunotherapeutic approaches. We discuss the dynamic phenotypic and functional heterogeneity of tumor-associated macrophages (TAMs), their impact on disease progression, and the mechanisms underlying their response to immunotherapy. Furthermore, we highlight recent advancements in macrophage-based immunotherapeutic strategies, including macrophage-targeting agents, adoptive cell transfer, and engineering approaches. Understanding the complex crosstalk between macrophages and the TME is essential for developing effective immunotherapeutic interventions that exploit the immunomodulatory functions of macrophages to enhance anti-tumor immunity and improve clinical outcomes for cancer patients.

Reduction of clinically irrelevant alarms in patient monitoring by adaptive time delays.

The problem of high rates of false alarms in patient monitoring in anesthesiology and intensive care medicine is well known but remains unsolved. False alarms desensitize the medical staff, leading to ignored true alarms and reduced quality of patient care. A database of intra-operative monitoring data was analyzed to find characteristic alarm patterns. The original data were re-evaluated to find relevant events and to rate the severity of these events. Based on this analysis an adaptive time delay was developed that individually delays the alarms depending on the grade of threshold deviation. The conventional threshold algorithm led to 4893 alarms. 3515 (71.84 %) of these alarms were annotated as clinically irrelevant. In total 81.0 % of all clinically irrelevant alarms were caused by only mild and/or brief threshold violations. We implemented the new algorithm for selected parameters. These parameters equipped with adaptive validation delays led to 1729 alarms. 931 (53.85 %) alarms were annotated as clinically irrelevant. 632 alarms indicated the 645 clinically relevant events. The positive predictive value of occurring alarms improved from 28.16 % (conventional algorithm) to 46.15 % (new algorithm). 13 events were missed. The false positive alarm reduction rate of the algorithm ranged from 33 to 86.75 %. The overall reduction was 73.51 %. The implementation of this algorithm may be able to suppress a large percentage of false alarms. The effect of this approach has not been demonstrated but shows promise for reducing alarm fatigue. Its safety needs to be proven in a prospective study.

Transcapsular arterial neovascularization of liver transplants increases the risk of intraoperative bleeding during retransplantation.

Arterial neovascularization of liver grafts can be a source of significant blood loss during retransplantation. This study evaluated the effect of transcapsular arterial neovascularization on intraoperative blood loss during retransplantation and long-term follow-up. Eleven consecutive patients with transcapsular arterial neovascularization (seven male, four female; nine children, two adults; mean age 12.3 ± 16.3 years) and the same number of matched control patients were analysed. Blood loss was calculated based on transfusion requirements. The volume of transfused units of red blood cells per kilogram bodyweight until hepatectomy and during the entire procedure was significantly higher in patients with neovascularization than in control patients (0.32 ± 0.21 vs. 0.14 ± 0.11, and 0.94 ± 0.83 vs. 0.36 ± 0.38 respectively; P-values 0.027). Neovascularization was associated with extensive intra-abdominal adhesions and a longer operating time until hepatectomy (175.6 ± 52.1 min vs. 124.3 ± 34.9 min, P-value 0.015). Postoperative revisions were performed more frequently in patients with neovessels. Graft survival did not differ between groups. Assessment for transcapsular arterial neovascularization should be included in preoperative Doppler ultrasound protocols to identify patients at risk of a complicated intra- and postoperative course in case of retransplantation.

Biogenic Analysis of the Effect of TERC on Cell Proliferation and Migration of Oral Squamous Cell Carcinoma under Digital Minimally Invasive Treatment.

Objective: To investigate the correlation between TERC gene and cell proliferation and migration of oral squamous cell carcinoma. Methods: By comparing the traditional surgical treatment with the minimally invasive treatment of digital technology, the influence of Shengxin analysis method on the proliferation and migration of oral squamous cell carcinoma cells was analyzed. Results: Digital technology minimally invasive treatment has a great impact on the operation and survival rate of patients. TERC has a significant impact on the proliferation and migration of oral squamous cell carcinoma cells. Digital technology minimally invasive treatment can prevent TERC from great changes. Conclusion: TERC under the minimally invasive treatment of digital technology has little effect on the proliferation and migration of oral squamous cell carcinoma cells. It can promote the proliferation of oral squamous cell carcinoma cells. The inhibitors of migration and invasion can play an effective role in antiproliferation.

The wolf is crying in the operating room: patient monitor and anesthesia workstation alarming patterns during cardiac surgery.

BACKGROUND: Vital sign monitors and ventilator/anesthesia workstations are equipped with multiple alarms to improve patient safety. A high number of false alarms can lead to a "crying wolf" phenomenon with consecutively ignored critical situations. Systematic data on alarm patterns and density in the perioperative phase are missing. Our objective of this study was to characterize the patterns of alarming of a commercially available patient monitor and a ventilator/anesthesia workstation during elective cardiac surgery. METHODS: We performed a prospective, observational study in 25 consecutive elective cardiac surgery patients. In all patients, identically fixed alarm settings were used. All incoming patient data and all alarms from the patient monitor and the anesthetic workstation were digitally recorded. Additionally, the anesthesia workplace was videotaped from 2 different angles to allow retrospective annotation and correlation of alarms with the clinical situation and assessment of the anesthesiologists' reaction to the alarms. RESULTS: Of the 8975 alarms, 7556 were hemodynamic alarms and 1419 were ventilatory alarms. For each procedure, 359 ± 158 alarms were recorded, representing a mean density of alarms of 1.2/minute. CONCLUSION: Approximately 80% of the total 8975 alarms had no therapeutic consequences. Implementation of procedure-specific settings and optimization in artifact and technical alarm detection could improve patient surveillance and safety.

Endovascular treatment of malignant superior vena cava syndrome: is bilateral wallstent placement superior to unilateral placement?

PURPOSE: To report our experience with unilateral versus bilateral stent placement in the treatment of malignant superior vena cava syndrome (SVCS). METHODS: The records and films of 84 consecutive patients (69 men; mean age 64+/-10 years, range 39-79) referred for stent placement in malignant SVCS were reviewed for venous compromise, technical and clinical success, complications, and reocclusions. Wallstents were placed covering the SVC and both (bilateral technique) brachiocephalic veins (BCV) preferentially; unilateral stenting of only one BCV in addition to the SVC was performed based on operator preference or inability to access both sides. Technical success was defined as the ability to stent the SVC and at least one BCV; clinical success was the elimination of SVCS symptoms. RESULTS: Technical success was achieved in 83 (99%) patients, using the unilateral technique in 22 and bilateral stenting in 61 patients. The groups did not differ with regard to age, sex, underlying diseases, or location and extent of venous compromise. Immediate clinical success was achieved in 20 (91%) of 22 patients in the unilateral group and 55 (90%) of 61 patients in the bilateral group. Two patients suffered late occlusion in the unilateral group, while in the bilateral group, 8 patients had early occlusion and 9 had late occlusion. Thus, the total occlusion rate was significantly (p<0.05) lower in the unilateral group. There was 1 other complication (pericardial tamponade) in the bilateral group, for a 28% total complication rate, which was significantly higher (p=0.039) than the 9% in the unilateral group. The 1, 3, 6, and 12-month primary stent patency rates were 90%, 81%, 76%, and 69%, respectively. Patency tended to last longer in the unilateral group, but the difference was not significant (p=0.11). CONCLUSIONS: Although bilateral Wallstent placement achieved equal technical and clinical success, it tended to confer shorter-lived patency and caused more complications.