Search Results (100)

Background: While trefoil factor 3 (TFF3) has been linked to cardiovascular disease, its role in peripheral artery disease (PAD) remains largely unexplored. In this prospective study, we assessed three pre-selected circulating biomarkers and found that TFF3 demonstrated the strongest association with the presence of PAD. Building on this finding, we integrated plasma TFF3 concentrations with clinical characteristics to construct predictive models aimed at identifying individuals with PAD and estimating their risk of major adverse limb events (MALE) over a two-year follow-up period. Methods: A total of 476 individuals were prospectively recruited, including 312 patients with PAD and 164 controls without PAD. At study entry, circulating concentrations of TFF3, oncostatin M (OSM), and brain-derived neurotrophic factor (BDNF) were quantified, and all participants were subsequently monitored for a two-year period. The primary endpoint was the occurrence of MALE within two years, comprising acute limb ischemia, major amputation, or lower extremity revascularization by either open surgical or endovascular approaches. PAD diagnosis served as the secondary outcome and was established by an ankle–brachial index (ABI) ≤ 0.9 or toe–brachial index (TBI) ≤ 0.67 in the presence of reduced or absent pedal pulses. For predictive model development, the cohort was randomly divided into training (70%) and testing (30%) sets. A random forest algorithm incorporating clinical variables and plasma TFF3 levels was developed and optimized using 10-fold cross-validation. Model discrimination was quantified using the area under the receiver operating characteristic curve (AUROC). For prognostic evaluation, patients were classified into low- and high-risk groups based on the optimal ROC-derived probability threshold of 0.60, and MALE-free survival between groups was assessed using Cox proportional hazards regression. Results: Among the three candidate biomarkers evaluated, only TFF3 demonstrated a significant association with PAD. Patients with PAD exhibited higher circulating TFF3 concentrations than those without PAD (7.27 ± 3.36 vs. 5.89 ± 2.67 pg/mL; p < 0.001), whereas OSM and BDNF showed no significant differences between groups. Over the two-year follow-up period, MALE occurred in 28 patients (9%). Predictive models combining plasma TFF3 measurements with clinical variables achieved strong performance for both PAD detection and 2-year MALE risk estimation, yielding AUROCs of 0.79 and 0.85, respectively. Furthermore, patients classified as high risk by the model experienced a significantly increased hazard of MALE during follow-up (HR 1.12, 95% CI 1.10–1.19; p = 0.003). Variable importance analysis revealed that TFF3 was the most influential predictor of MALE, followed by age and smoking history. Conclusions: Combining plasma TFF3 levels with readily available clinical characteristics enabled the development of a predictive model with good discriminatory ability for both PAD diagnosis and estimation of 2-year MALE risk. Such an approach may enhance risk stratification by identifying patients at elevated risk earlier in their disease course, thereby informing decisions related to vascular testing, referral for specialist evaluation, and implementation of targeted treatment strategies. Full article

Background and Clinical Significance: Acute compartment syndrome is a rare but limb-threatening emergency in pediatric patients. While most cases follow high-energy trauma or displaced fractures, acute compartment syndrome precipitated by initially underestimated forearm injuries is uncommon and may create a significant diagnostic challenge, particularly in young children who exhibit atypical clinical presentations, such as escalating anxiety and analgesic requirements, rather than classic ischemic signs. Case Presentation: We report the case of a 4-year-old girl who developed severe forearm and hand compartment syndrome following a delayed presentation after a fall from a height of 2–2.5 m onto the left upper extremity. Initial evaluation revealed progressive tense swelling, severe pain with passive stretch, diminished distal perfusion, and radiographic evidence of distal radius-ulna buckle fractures associated with a proximal ulna fracture. Emergent surgical decompression via extensive volar and dorsal fasciotomies revealed markedly elevated compartment pressures. Intraoperatively, deep volar muscle ischemia and necrosis were identified, requiring carpal tunnel release, serial debridements, and complex staged wound management. Multidisciplinary care and ongoing rehabilitation were essential for limb salvage and functional recovery. Conclusions: This case underscores the profound unpredictability of pediatric compartment syndrome and demonstrates that even classically stable, benign fractures can initiate a devastating ischemic cascade. A high index of suspicion, regardless of the injury mechanism, along with early recognition and prompt surgical intervention, is absolutely critical for preventing irreversible myoneural damage and optimizing management outcomes in pediatric patients. Full article

Background: Refractory cardiac arrest, cardiogenic shock, and severe acute respiratory failure remain associated with substantial mortality despite advances in advanced life support and extracorporeal membrane oxygenation (ECMO). Transportable ECMO platforms may enable rapid deployment, uninterrupted extracorporeal support, and safer in-hospital transport, but early real-world experience with newer systems remains limited. Methods: We conducted a retrospective single-center observational cohort study including all VitalFlow veno-arterial ECMO (VA-ECMO) and veno-venous ECMO (VV-ECMO) deployments performed between November 2025 and March 2026 at a high-volume tertiary cardiac surgery center. Fifteen cases were analyzed, comprising 12 VA-ECMO and 3 VV-ECMO deployments. Data were extracted from electronic health records, perfusion protocols, and ICU documentation. Outcomes included survival to hospital discharge, 30-day survival, neurological outcomes, and complications. Analyses were descriptive. Results: The cohort was exclusively male and clinically unstable at implantation, with high lactate and low pH levels consistent with severe hypoperfusion. Median time-to-flow was 33 min, and median ECMO duration was 8 days. Survival to discharge was 60% overall (66.7% VA-ECMO, 33.3% VV-ECMO), with ECMO weaning success in 86.7% and the primary death cause being multiorgan failure (83.3% of non-survivors). All survivors achieving a favorable neurologic outcome (CPC 1). Thirty-day survival was 73.3%. No major bleeding or stroke occurred. Limb ischemia was observed in 4 patients, with 2 patients requiring fasciotomy, all in the VA-ECMO group. Bronchial infection occurred in 3 patients. Lactate levels improved within the first 24 h, and survivors showed a more pronounced metabolic response. Conclusions: In this early single-center experience, VitalFlow ECMO was feasible and associated with rapid flow establishment, survival to discharge of 60% of patients, and good neurologic outcome among survivors. The complication profile was acceptable, with limb ischemia as the main adverse event. These findings support further evaluation of this transportable ECMO platform in larger multicenter cohorts. Full article

Background: Acute limb ischemia (ALI) is a vascular emergency characterized by abrupt limb hypoperfusion, ischemia–reperfusion injury, and a high risk of thromboinflammatory and organ complications. Complement activation has been implicated in endothelial dysfunction, glycocalyx injury, and ischemia–reperfusion damage, but the clinical relevance of ongoing terminal complement blockade in patients presenting with ALI remains unclear, highlighting a gap between mechanistic understanding and real-world clinical outcomes. Methods: A retrospective cohort study was performed using the TriNetX federated research network. Adult patients with ALI were identified and stratified according to ongoing treatment with the C5 inhibitors eculizumab or ravulizumab. Outcomes included ischemic stroke, venous thrombosis, pulmonary embolism, arterial embolism, thrombotic disorders, acute kidney injury (AKI), and the composite outcome major adverse cardiovascular events (MACE) within 31 days. Propensity score matching was performed for demographic characteristics, cardiovascular comorbidities, complement-associated diseases and medications. Results: After propensity score matching, 112 patients remained in each cohort. Compared with matched controls, patients receiving C5 inhibition had a significantly higher risk of venous thrombosis (27.9% vs. 13.7%; p < 0.001), AKI (18.9% vs. 9.4%; p = 0.001), MACE (50.0% vs. 35.1%; p = 0.001), and thrombotic disorders (46.7% vs. 31.3%; p = 0.001). Time-to-event analyses confirmed significantly lower event-free survival for venous thrombosis (HR 2.3), AKI (HR 2.1), MACE (HR 1.6), and thrombotic disorders (HR 1.7). No significant differences were observed for ischemic stroke, pulmonary embolism, or arterial embolism. Conclusions: In patients with ALI, ongoing treatment with eculizumab or ravulizumab was not associated with an apparent reduction in short-term thromboinflammatory or cardiovascular complications. Instead, the observed outcome pattern suggests persistent vulnerability in this clinically uncommon but increasingly relevant high-risk population, although substantial residual confounding by indication and disease severity remains likely. These findings support further investigation of complement-targeted therapy, endothelial injury, and short-term vascular outcomes in ALI, and emphasize the translational relevance of linking mechanistic insights with clinical data to inform risk stratification and management strategies in this population. Full article

Background: Peripheral artery disease (PAD) impacts more than 200 million individuals globally. Despite its prevalence, management remains suboptimal, partly due to the lack of reliable blood-based biomarkers. The ankle–brachial index (ABI), the current gold-standard test for PAD, is limited by inter-operator variability, misinterpretation, and reduced accuracy in patients with diabetes. Fatty acid binding protein 3 (FABP3) has emerged as a potential biomarker for PAD; however, its prognostic performance relative to ABI remains unclear. This study compared FABP3 and ABI for predicting PAD outcomes using statistical and machine learning approaches. Methods: A total of 1001 participants were prospectively recruited, including 644 patients with PAD and 357 without PAD. The primary outcome was 2-year major adverse limb event (MALE), defined as a composite of vascular intervention, major amputation, or acute limb ischemia. At enrollment, plasma FABP3 was quantified using a validated multiplex immunoassay. Kaplan–Meier analysis of MALE-free survival was performed across pre-specified FABP3 tertiles (high [>3.55 ng/mL], moderate [1.55–3.55 ng/mL], and low [<1.55 ng/mL]) and ABI tertiles (severe [<0.40], moderate [0.40–<0.70], and mild [0.70–0.90]), with curve separation assessed using log-rank tests. Multivariable Cox proportional hazards modelling was used to evaluate the independent relationships of FABP3 and ABI with 2-year MALE after adjustment for baseline demographic and clinical covariates. To assess predictive performance for 2-year MALE, an extreme gradient boosting (XGBoost) classification model incorporating 10-fold cross-validation was trained using a combination of clinical covariates, plasma FABP3 levels, and ABI. Discriminatory performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: The average participant age was 68 years (SD 12), and 34% (n = 340) were women. Mean ABI was 0.75 ± 0.25 and mean FABP3 concentration was 2.97 ± 2.06 ng/mL. Among the 644 participants with PAD, 558 (86.6%) had complete time-to-event data for MALE status, FABP3, and ABI. Over the median follow-up period of 2 years, 140 (25.1%) participants with PAD experienced MALE. Kaplan–Meier analyses demonstrated significant separation in MALE-free survival across FABP3 tertiles (log-rank p < 0.001). At 24 months, MALE-free survival was 100.0% in the FABP3 < 1.55 group, compared with 71.1% in the FABP3 1.55–3.55 group and 67.7% in the FABP3 > 3.55 group. In contrast, ABI severity groups showed less pronounced separation, with 24-month MALE-free survival rates of 80.3% for mild ABI, 73.2% for moderate ABI, and 71.3% for severe ABI, without a statistically significant overall difference (p = 0.170). In adjusted Cox proportional hazards models, FABP3 demonstrated strong prognostic performance for 2-year MALE. A 1 SD increase in log-transformed FABP3 was independently associated with a higher risk of 2-year MALE (HR 1.90, 95% CI 1.60–2.25; p < 0.001), with minimal change after additional adjustment for ABI (HR 1.90, 95% CI 1.60–2.24; p < 0.001). Machine learning analyses similarly favored FABP3 over ABI, with the FABP3-based model achieving an AUC of 0.773 compared to 0.686 for the ABI-based model. Adding ABI to the FABP3 model did not improve discrimination. Conclusions: Circulating plasma levels of FABP3 are strongly associated with PAD outcomes. Specifically, FABP3 demonstrated a stronger and more robust association with 2-year MALE compared to ABI. This study validates the prognostic value of FABP3 for PAD outcomes in comparison to ABI. Full article

Background: Acute type A aortic dissection (ATAAD) is a life-threatening condition that may be complicated by malperfusion, particularly in patients with prior aortic interventions such as Thoracic Endovascular Aortic Repair (TEVAR). Management becomes increasingly complex when the dissection involves supra-aortic branches and compromises previously placed stents. Methods: We report the case of a 58-year-old male presenting with ATAAD and left lower limb paralysis, with a history of prior TEVAR. Imaging demonstrated an entry tear in the ascending aorta with extension into the distal left main and supra-aortic branches, resulting in a dissection flap obstructing the proximal end of the TEVAR stent. The patient underwent emergency surgical intervention including a Bentall procedure, coronary artery bypass grafting (CABG), and deployment of a small Ascyrus Medical Dissection Stent (AMDS) distally within the TEVAR stent. Pre-operatively, the patient had severe lower limb ischemia due to near-complete obstruction of distal flow. Results: Following surgical intervention, there was restoration of true lumen perfusion with resolution of malperfusion. The patient was successfully weaned from cardiopulmonary bypass, extubated on post-operative day 4, and discharged on day 7 with stable hemodynamics and intact bilateral lower limb perfusion. Post-operative computed tomography (CT) demonstrated a well-seated AMDS with no evidence of ongoing false lumen perfusion. At 30-day follow-up, there was no clinical or biochemical evidence of organ malperfusion. Conclusions: The use of an AMDS deployed within a pre-existing TEVAR stent may represent an effective strategy for managing complex ATAAD with malperfusion, particularly in cases requiring combined surgical interventions. Full article

Background: Combat-related lower extremity injuries frequently require prolonged tourniquet application to control life-threatening hemorrhage. Although effective for hemorrhage control, prolonged ischemia followed by reperfusion substantially increases the risk of rhabdomyolysis, acute kidney injury (AKI), limb loss, and mortality. The optimal timing of anti-rhabdomyolysis infusion therapy in relation to tourniquet release remains uncertain. Methods: This retrospective single-center cohort study analyzed 120 Ukrainian military casualties with combat-related lower extremity injuries requiring prolonged tourniquet application and subsequent surgical management, including fasciotomy and tourniquet release. Patients were divided into two groups based on infusion strategy: standard therapy initiated after tourniquet release and early anti-rhabdomyolysis infusion therapy initiated before tourniquet removal during the ischemic phase. Primary outcomes included dialysis-requiring AKI, limb amputation, and death. Multivariable logistic regression models were adjusted for baseline physiological severity, including shock index at admission and baseline acid–base status. Model performance was evaluated using the Akaike Information Criterion (AIC) and receiver operating characteristic (ROC) analysis. Propensity score–based inverse probability of treatment weighting (IPTW) was applied as a sensitivity analysis. Results: After adjustment, early infusion therapy was independently associated with lower rates of dialysis-requiring AKI (adjusted odds ratio [OR] 0.33; 95% confidence interval [CI] 0.13–0.84; p = 0.020), limb amputation (OR 0.32; 95% CI 0.11–0.95; p = 0.040), and mortality (OR 0.23; 95% CI 0.07–0.77; p = 0.017). Adjusted models demonstrated good discriminative ability, with areas under the ROC curve of 0.813 for AKI, 0.838 for amputation, and 0.823 for mortality. Sensitivity analyses using IPTW yielded consistent results. Conclusions: In combat-related lower extremity injuries requiring prolonged tourniquet application, early initiation of anti-rhabdomyolysis infusion therapy prior to reperfusion is associated with significantly reduced risks of severe AKI, limb loss, and death. These findings suggest that preventive renal-protective strategies initiated before tourniquet release may improve outcomes in high-risk military trauma settings and warrant further prospective investigation. Full article

Type B aortic dissection (TBAD) requires management tailored to the disease phase and clinical presentation, with the subacute period representing a favorable window for endovascular intervention due to improved procedural safety and remodeling potential. We report the case of a 38-year-old male with hypertension, dyslipidemia, and bicuspid aortic valve disease who presented one month after symptom onset with persistent chest pain and progressive bilateral lower-limb numbness. Clinical examination suggested early spinal cord ischemia, while laboratory tests demonstrated acute hepatic and renal dysfunction. CT angiography revealed a subacute TBAD with a markedly expanded false lumen and near-complete compression of the true lumen, resulting in visceral, renal, and potential spinal malperfusion. Given the high-risk anatomy and evolving organ dysfunction, a staged hybrid strategy was undertaken. A left carotid–subclavian bypass was performed to secure proximal landing for endovascular repair, followed the next day by thoracic endovascular aortic repair (TEVAR) using two thoracic stent grafts. Postoperative recovery was favorable, with rapid resolution of neurological symptoms and normalization of hepatic and renal parameters, allowing discharge on postoperative day seven. This case underscores the importance of early recognition of malperfusion and timely hybrid intervention in subacute TBAD with severely compressed true lumen, demonstrating excellent early clinical outcomes. Full article

Background: Acute infrainguinal bypass graft occlusion is a critical vascular emergency that threatens limb viability and challenges both surgical and endovascular management. Despite progress in revascularization strategies, outcomes remain suboptimal, and consensus on the optimal treatment approach is lacking. Methods: This narrative review summarizes current evidence on the epidemiology, etiology, diagnosis, and treatment of acute infrainguinal graft occlusion. Particular attention is given to the evolving role of catheter-directed thrombolysis and mechanical thrombectomy, as well as to prevention strategies based on structured surveillance and medical optimization. Results: Infrainguinal bypass failure is influenced by technical, anatomical, and systemic factors, with distinct mechanisms affecting vein and prosthetic grafts. While surgical thrombectomy remains a viable option in selected cases, endovascular techniques have gained prominence due to their minimally invasive nature and promising short-term outcomes. Prevention of occlusion through duplex surveillance and best medical therapy is crucial to preserving graft patency and reducing major amputation risk. Conclusions: Management of acute graft occlusion requires timely diagnosis and a tailored, multidisciplinary approach. Although endovascular therapies have expanded treatment options, further prospective studies are needed to define optimal strategies and improve long-term outcomes in this high-risk population. Full article

The myeloproliferative neoplasms (MPN), a heterogeneous group of disorders characterized by specific genetic mutations, have the development of arterial and venous thrombosis as their main complication. Almost 40–50% of MPN patients encountered arterial or venous thrombosis during the course of their disease. Moreover, arterial thrombosis is linked to significant mortality, progression to myelofibrosis, and an increased risk of developing second cancers. Despite significant advancements in medical research, there are still unmet needs in this field. Our narrative review provides clinical and genetic insights into thrombosis associated with myeloproliferative neoplasms. We focus on the underlying pathophysiological processes, assessment methods, and risk stratification related to thrombotic events. This information aims to assist clinicians in accurately assessing the risks associated with MPN thrombosis, enabling a more personalized and effective approach to patient care. We based our review on a rare case of MPN-associated thrombosis, whose clinical presentation was marked by acute ischemia in both lower limbs. The thrombosis affected the distal aortic arch, thoracic and abdominal aorta, celiac trunk, common and proper hepatic arteries, proximal left renal artery, several segmental arteries in the right kidney, and the portal vein thrombosis. Our review presents various therapeutic options for these conditions. In the presented case, the multiple thrombi were treated medically, except for the popliteal artery thromboses, which required surgical management. This case may serve as a valuable reference for choosing treatment options for aortic and portal vein thrombosis, highlighting the multidisciplinary approach. Full article

Background/Objectives: The diagnosis of acute compartment syndrome (ACS) of the extremities is typically based on subjective clinical signs and symptoms, highlighting the need for user-friendly diagnostic tools to improve accuracy and reliability. This study evaluates the performance of two commercial devices, the MY01^® continuous pressure monitoring system and the Moxy Monitor near-infrared spectroscopy-based system, against a reference standard of continuous intracompartmental pressure (ICP) monitoring in a preclinical ACS model. Methods: ACS was induced in the anterior compartment of the distal hind limb in eight Yorkshire pigs using a balloon displacement model. ICP was incrementally elevated and maintained for four hours at >30 mmHg above mean arterial pressure. This was followed by balloon deflation and reperfusion. Final assessments were performed at 24 h post-injury. ICP measurements from the MY01^® and muscle oxygen saturation (SmO₂) data from the Moxy Monitor were compared to reference ICP measurements. Histologic analysis of muscle tissue was performed to assess the severity of necrosis. Results: The MY01^® provided accurate ICP measurements, with a mean bias of 2.21 ± 18.77 mmHg during pre-ischemia, 4.86 ± 10.43 mmHg during reperfusion, and 4.69 ± 3.28 mmHg 24 h post-injury, compared to reference probes. Correlation at 24 h post-injury was (r = 0.86, R² = 0.73, p < 0.0001). In contrast, the Moxy Monitor failed to detect significant differences in SmO₂ between injured and control limbs at 24 h post-injury, despite pronounced ICP differences. Our volumetric displacement ACS model demonstrated its efficacy as a testing platform by allowing for controlled, incremental elevation in ICP and sustaining elevated ICP levels after 24 h. Histologic evaluation confirmed extensive muscle damage, including edema and necrosis. Conclusions: The MY01^® provides accurate, continuous ICP monitoring, supporting its clinical utility in ACS diagnosis. However, the use of near-infrared spectroscopy-based systems such as the Moxy Monitor for ACS diagnosis and management should continue to be critically scrutinized. Full article

Peripheral artery disease is a common manifestation of atherosclerosis, characterized by insufficient tissue perfusion and chronic ischemia. Arteriogenesis and angiogenesis are essential endogenous mechanisms to restore blood flow and limit ischemic injury. The metalloprotease ADAMTS13, known for cleaving ultra-large von Willebrand factor, has been implicated in thrombotic and inflammatory regulation. However, its role in ischemic vascular remodeling remains unclear. Using a murine hind limb ischemia model, we investigated the effect of ADAMTS13 deficiency on arteriogenesis and angiogenesis by comparing male ADAMTS13^−/− and wild-type control mice. Perfusion recovery, vascular cell proliferation, immune cell infiltration, and thrombotic activity were evaluated using laser Doppler measurements, immunohistochemical analysis of adductor and gastrocnemius muscle tissues, and in vivo microscopy. ADAMTS13 deficiency did not impair perfusion recovery, collateral artery growth, or capillarization. While platelet adhesion was slightly increased in ADAMTS13^−/− mice, no thrombotic occlusions were observed. Inflammatory responses, including macrophage and neutrophil infiltration as well as macrophage polarization, were largely unaffected. Despite previous in vitro evidence indicating an angiogenic role for ADAMTS13, its absence did not compromise angiogenesis in vivo. Our findings suggest that ADAMTS13 does not play a critical role in ischemia-related angiogenesis and arteriogenesis under sterile conditions and may be relevant only in contexts involving acute and sufficiently strong thromboinflammatory stimuli. Full article

Complete detachment of a cardiac myxoma represents an exceptionally rare but potentially catastrophic complication. This case report describes a young female patient who developed acute abdominal pain following vigorous physical exertion, with rapid progression to visceral ischemia and bilateral lower limb ischemia within an extremely short timeframe. Comprehensive diagnostic imaging and postoperative pathological examination confirmed this as a remarkably rare case of complete cardiac myxoma detachment. This condition has been reported in only a handful of cases in the existing medical literature. Full article

Background: Acute aortic occlusion (AAO) is a rare but life-threatening condition which can present with a spectrum of symptoms, ranging from mild cramping pain in the lower extremities (with or without sensory loss) to more dramatic motor loss and paraplegia. Once a diagnosis has been established, the treatment remains ambiguous, especially in a resource-limited setting. Treatment ranges from direct vascular intervention to systemic or directed thrombolysis—however, there is a lack of published literature on systemic thrombolysis, and thereby, consensus guidelines are nonexistent. Additionally, systemic thrombolysis bears a risk of hemorrhagic complications; however, the risk of death due to AAO is up to 57 times greater than the risk of intracerebral hemorrhage from systemic thrombolysis. Methods: This case report explores the prompt diagnosis of an acute aortic occlusion causing bilateral acute lower extremity ischemia in a sixty-three-year-old female patient treated with systemic thrombolysis. Results: The patient received 100 mg of tPA (without a bolus dose, over a two-hour period) in the Emergency Department (similar to that which is administered for the full-dose pulmonary embolism protocol). One hour after administration, the patient had restored flow to the bilateral lower extremities verified using bedside color-flow Doppler, with a drastic improvement in her symptoms. Two days after systemic thrombolysis, a repeat CTA showed evidence of complete resolution of her aortic clot. Her condition was complicated by a brief episode of retroperitoneal bleeding (presenting with flank pain) while on a heparin drip after admission (day two), which was resolved through discontinuation of the heparin drip and a two-unit blood transfusion. Conclusion: The patient was discharged with full function of the lower extremities on day six without anticoagulation. At her 2-week follow-up appointment, she was noted to be ambulatory without any neurodeficit, with a persistently restored arterial flow to the lower extremity. The application of systemic tPA could be paramount in the treatment of AAO in the setting of ischemic limb pathology, particularly at rural hospitals and healthcare centers where urgent direct vascular intervention may not be possible. Full article

Background: Unvaccinated individuals with peripheral arterial occlusive disease (PAOD) are more likely to develop acute limb ischemia (ALI) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We assessed the protective effect of the COVID-19 vaccine in preventing ALI in PAOD patients with SARS-CoV-2 infection. Methods: This retrospective cohort study was conducted using the United States TriNetX (Cambridge, MA, USA), using patients with PAOD who were diagnosed with SARS-CoV-2 infection between 1 November 2020 and 31 December 2023. Propensity score matching was performed to adjust for demographic variables, lifestyle factors, medical utilization, and comorbidities. Cox proportional hazards models were used to compare the two matched cohorts. Kaplan–Meier analysis estimated the 3-year cumulative probability of lower limb amputation incidence. We selected 12,948 PAOD patients who received the COVID-19 vaccine and 44,064 PAOD patients who were unvaccinated against COVID-19. Results: A total of 11,822 pairs of COVID-19 vaccinated PAOD patients and unvaccinated individuals were compared. The mean (SD) age was 66.5 (14.1) years; there were 4849 male patients (41%) and 6569 female (55.6%) compared to unvaccinated PAOD patients, and those who received the COVID-19 vaccine had a significantly lower risk of 3-year all-cause mortality (log-rank test, p < 0.001; hazard ratio (HR) was 0.857; 95% CI, 0.796–0.922) and lower limb amputation (log-rank test, p = 0.001, HR = 0.716; 95% CI, 0.587–0.873), though there was no significant difference in ischemic stroke (log-rank test, p = 0.174; HR = 0.958; 95% CI, 0.902–1.019). Conclusions: This study found that patients who received the COVID-19 vaccine had a significantly lower risk of 3-year all-cause mortality and lower limb amputation, though there was no significant difference in ischemic stroke. Full article