antithrombin III (Atenotiv / ATenativ / ATnativ)

Immune regulation includes an effector arm: therapeutic implications of phase III IDO/PD-L1 vaccination in melanoma.

Andersen Mads Hald MH

Ischemic Limb Necrosis and Symmetrical Peripheral Gangrene During Vasopressor Support in Severe Shock States: Thromboinflammatory Microvascular Injury as the Pathogenic Mechanism.

Levy Jerrold H JH, Shaw Joseph R JR, Connors Jean M JM, Draxler Dominik F DF et al.

Ischemic limb necrosis and resulting symmetrical peripheral gangrene (SPG) are devastating complications of severe shock states, particularly septic shock, and are associated with major morbidity, limb loss, and mortality. These complications usually occur in patients requiring vasopressor support for cardiovascular resuscitation during profound circulatory collapse. In this setting, however, thromboinflammatory microvascular injury represents the principal mechanism underlying ischemic tissue injury. Life-threatening shock is characterized by endothelial injury, glycocalyx disruption, disseminated intravascular coagulation (DIC), impaired fibrinolysis, and ischemic hepatic injury ("shock liver") with endogenous natural anticoagulant factor depletion (antithrombin, protein C, protein S) that promotes diffuse thromboinflammatory microvascular thrombosis and impaired tissue perfusion independent of vasopressor therapy. Importantly, most critically ill patients receiving prolonged or high-dose vasopressor therapy do not develop ischemic limb necrosis in the absence of severe coagulopathy, DIC, or shock liver. In contrast, patients developing SPG typically exhibit DIC (severe thrombocytopenia, greatly elevated D-dimer levels), hepatic dysfunction, and multiorgan failure. Under these conditions, progressive microthrombosis in distal limbs produces acral ischemia and tissue necrosis. This review examines SPG in severe shock states through the framework of thromboinflammatory microvascular dysfunction, hepatic dysfunction, dysregulated coagulation with natural anticoagulant depletion, and endothelial injury, culminating in acral microthrombosis; we evaluate key limitations and confounders in the literature on vasopressor-associated ischemia; and discuss the clinical phenotype of SPG in septic shock and critical illness. Finally, we address some of the important clinical and treatment implications of ischemic limb necrosis during vasopressor support in critically ill patients with shock.

Impact of the Australian National Bowel Cancer Screening Program on Stage at Diagnosis and Stage-Specific Survival in Colorectal Cancer.

Rouse Michael M, Harold Michael M, Wong Vanessa V, Lee Margaret M et al.

The Australian National Bowel Cancer Screening Program began in 2006, offering free faecal occult blood testing every 2 years to Australians aged 50-75 years. We hypothesised a difference in overall survival between screen-detected and non-screen-detected colorectal cancer in an Australian cohort, for each stage I-III. A retrospective cohort study of patients with stage I-III colorectal cancer from 2010 to 2024 was conducted using a prospectively maintained institutional database. Overall survival (OS) was calculated from the date of diagnosis. Kaplan-Meier analysis and log-rank testing were used to compare survival between screen-detected and non-screen-detected cancers, stratified by stage. A total of 881 colorectal cancer episodes were included, of which 254 (28.8%) were screen-detected. The proportion of screen-detected cancers increased significantly over time (Cochran-Armitage trend test, p < 0.001). Screen-detected cancers were diagnosed at an earlier stage, with a significantly higher proportion of stage I disease than non-screen-detected cancers (38.6% vs. 18.0%, p < 0.001). Five-year OS for stage I disease was 93.9% in the screen-detected group and 90.8% in the non-screen-detected group (HR 0.62, 95% CI 0.30-1.28; p = 0.19). Corresponding five-year OS for stage II disease was 91.3% and 85.6%, respectively (HR 0.70, 95% CI 0.33-1.48; p = 0.35). In stage III disease, 81.5% vs. 68.9%, respectively (HR 0.56, 95% CI 0.34-0.92; p = 0.02). Screen-detected colorectal cancer is associated with earlier stage at diagnosis and improved survival in stage III disease. These findings support the role of screening in earlier diagnosis and improved oncological outcomes.

Severe anaphylactic shock suspectedly induced by injection of recombinant humanized type III collagen lyophilized fiber for facial skin improvement: a case report.

Liu Junjie J, Yan Wenjing W, Liu Jing J, Yang Bowen B et al.

Recombinant humanized type III collagen is widely used in facial rejuvenation due to its excellent biocompatibility and overall favorable safety profile; however, severe systemic hypersensitivity reactions are exceedingly rare. We report a case of a 47-year-old woman with no prior history of allergy who received topical lidocaine to the face, followed by injection of recombinant humanized type III collagen lyophilized fibers for skin texture improvement. Immediately after the injection, she developed suspectedly severe anaphylactic shock temporally associated with the recombinant collagen injectionpresenting with confusion, respiratory distress, followed by marked bradycardia (33 beats/min), and loss of palpable arterial pulse. Emergency protocols were activated immediately, including cardiopulmonary resuscitation, intravenous adrenaline, corticosteroids, and fluid resuscitation. The patient's vital signs gradually recovered, and she was discharged after complete recovery two days later after complete recovery. This case suggests that recombinant humanized collagen, as a macromolecular protein, inherently carries the risk of triggering immediate-type anaphylactic shock despite its favorable safety profile. Clinicians should perform rigorous preoperative assessment, adhere to standardized procedures, and be proficient in the emergency management of anaphylactic shock to minimize the risk of severe adverse reactions and ensure medical safety.