Background: Symmetrical peripheral gangrene (SPG) is a destructive clinical condition where amputation is often the final treatment option. We aimed to identify the predictors of SPG using the common data model (CDM) and propose a new scoring system for predicting hospitalized patients at risk of developing SPG. Methods: A cohort of patients treated with intravenous noradrenaline, epinephrine, and vasopressin between 2011 and 2020 was retrospectively analyzed using the CDM database. The main outcome was amputation performed as a resuscitation measure. We investigated risk factors including demographic characteristics, comorbidities, and preoperative laboratory values. Based on demographic variables such as age and sex, a 1:10 propensity score matching (PSM) was performed. The odds ratio (OR) was calculated using logistic regression analysis. Results: Amputation was performed in 308 (0.4%) patients out of a cohort of 73,902 patients. Age, sex, hypertension, diabetes mellitus (DM), renal disease (RD), heart failure, anemia, hypercholesterolemia, peripheral vascular disease (PVD), and laboratory markers such as albumin, eosinophils, hematocrit, lymphocytes, monocytes, neutrophils, ESR, aPTT, creatinine, and BUN were statistically significant. Logistic regression analysis revealed statistically significant differences in DM (OR 5.51), RD (OR 2.90), PVD (OR 9.67), and cerebrovascular disease (CVD) (OR 0.49). Compared to the group without amputation, logistic regression analysis after matching the age and sex group with 1:10 PSM showed statistically significant results in DM (OR 3.59), RD (OR 2.59), PVD (OR 7.76), and CVD (OR 0.40). Conclusion: Early recognition of high-risk patients may help medical providers prevent severe outcomes, including amputation surgery.

Integrated diagnostic and therapeutic dressings are desirable to relieve diabetic patients who often suffer from diabetic foot ulcers (DFUs) and peripheral vascular diseases (PVDs). However, it is highly difficult to monitor the pulse waves with fidelity under wet environments and connect the waveforms to diseases through a small strain sensor. Additionally, immobilizing MXenzyme to regulate spatially heterogeneous levels of reactive oxygen species (ROS) and applying active intervention to enhance ulcer healing on a single structure remain a complex task. To address these issues, we designed a multiscale wearable dressing comprising a knitted all-textile sensing array for quantitatively investigating the pulse wave toward PVD diagnosis. MXenzyme was loaded onto the dressing to provide multiple enzyme mimics for anti-inflammatory activities and deliver electrical stimulation to promote wound growth. In mice, we demonstrate that high and uniform expression of the vascular endothelial growth factor (VEGF) is observed only in the group undergoing dual mediation with electrical stimulation and MXenzyme. This observation indicates that the engineered wound dressing has the capability to accelerate healing in DFU. In human patient evaluations, the engineered dressing distinguishes vascular compliance and pulse period, enabling the diagnosis of arteriosclerosis and return blockage, two typical PVDs. The designed and engineered multiscale dressing achieves the purpose of integrating diagnostic peripheral vessel health monitoring and ulcer healing therapeutics for satisfying the practical clinical requirements of geriatric patients.

BACKGROUND: Peripheral artery disease (PAD) in hemodialysis (HD) patients has a significant social impact due to its prevalence, poor response to standard therapy and dismal prognosis. Rheopheresis is indicated by guidelines for PAD treatment.
METHODS: Twenty-five HD patients affected by PAD stage IV Lerichè-Fontaine and ischemic ulcer 1C or 2C according to the University of Texas Wound Classification System (UTWCS), without amelioration after traditional medical therapy and/or revascularization, were selected and underwent 12 Rheopheresis sessions in 10 weeks. Improvements in pain symptoms using Numerical Rating Scale (NRS), healing ulcers and laboratory hemorheological parameters have been evaluated.
RESULTS: A clinically and statistically significant mean value reduction and of relative percentage differences between estimated marginal means (Δ), calculated at each visits, of NRS was observed, with a maximum value (-48.5%) between the first and last visit. At the end of the treatment period 14.3% of ulcers were completely healed, 46.4% downgraded, 53.6% were stable. Overall, no ulcers upgraded. A statistically significant reduction of the Δ, between the first and last visit, for fibrinogen (-16%) was also observed.
CONCLUSIONS: Rheopheresis reduced overall painful symptoms; data suggest that it could heal or improve ulcers and hemorheological laboratory parameters in HD patients with PAD and ischemic ulcers resistant to standard therapies.

Objective. Peripheral Vascular Disease (PVD) affects more than 230 million people worldwide and is one of the leading causes of disability among people over age 60. Nowadays, PVD remains largely underdiagnosed and undertreated, and requires the development of tailored diagnostic approaches. We present the full design of the Dynamic Extremity SPECT (DE-SPECT) system, the first organ-dedicated SPECT system for lower extremity imaging, based on 1 cm thick Cadmium Zinc Telluride (CZT) spectrometers and a dynamic dual field-of-view (FOV) synthetic compound-eye (SCE) collimator.Approach. The proposed DE-SPECT detection system consists of 48 1 cm thick 3D-position-sensitive CZT spectrometers arranged in a partial ring of 59 cm in diameter in a checkerboard pattern. The detection system is coupled with a compact dynamic SCE collimator that allows the user to select between two different FOVs at any time during an imaging study: a wide-FOV (28 cm diameter) configuration for dual-leg or scout imaging or a high-resolution and high-sensitivity (HR-HS) FOV (16 cm diameter) for single-leg or focused imaging.Main results.The preliminary experimental data show that the CZT spectrometer achieves a 3D intrinsic spatial resolution of <0.75 mm FWHM and an excellent energy resolution over a broad energy range (2.6 keV FWHM at 218, 3.3 keV at 440 keV). From simulations, the wide-FOV configuration offers a 0.034% averaged sensitivity at 140 keV and <8 mm spatial resolution, whereas the HR-HS configuration presents a peak central sensitivity of 0.07% at 140 keV and a ∼5 mm spatial resolution. The dynamic SCE collimator enables the capability to perform joint reconstructions that would ensure an overall improvement in imaging performance.Significance. The DE-SPECT system is a stationary and high-performance SPECT system that offers an excellent spectroscopic performance with a unique computer-controlled dual-FOV imaging capability, and a relatively high sensitivity for multi-tracer and multi-functional SPECT imaging of the extremities.

Aging is the greatest non-modifiable risk factor for most diseases, including cardiovascular diseases (CVD), which remain the leading cause of mortality worldwide. Robust evidence indicates that CVD are a strong determinant for reduced brain health and all-cause dementia with advancing age. CVD are also closely linked with peripheral and cerebral vascular dysfunction, common contributors to the development and progression of all types of dementia, that are largely driven by excessive levels of oxidative stress (e.g., reactive oxygen species [ROS]). Emerging evidence suggests that several fundamental aging mechanisms (e.g., \"hallmarks\" of aging), including chronic low-grade inflammation, mitochondrial dysfunction, cellular senescence and deregulated nutrient sensing contribute to excessive ROS production and are common to both peripheral and cerebral vascular dysfunction. Therefore, targeting these mechanisms to reduce ROS-related oxidative stress and improve peripheral and/or cerebral vascular function may be a promising strategy to reduce dementia risk with aging. Investigating how certain lifestyle strategies (e.g., aerobic exercise and diet modulation) and/or select pharmacological agents (natural and synthetic) intersect with aging \"hallmarks\" to promote peripheral and/or cerebral vascular health represent a viable option for reducing dementia risk with aging. Therefore, the primary purpose of this review is to explore mechanistic links among peripheral vascular dysfunction, cerebral vascular dysfunction, and reduced brain health with aging. Such insight and assessments of non-invasive measures of peripheral and cerebral vascular health with aging might provide a new approach for assessing dementia risk in older adults.

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OBJECTIVE: Comprehensive evaluation of lower-extremity varicose veins (VVs) in patients with diabetes is crucial for treatment strategizing. The study aims to assess the feasibility of using ferumoxytol-enhanced MR venography (FE-MRV) for lower-extremity venous mapping and the detection of VVs in patients with diabetes.
METHODS: As part of a phase II clinical trial of a generic brand of ferumoxytol, documented patients with diabetes were enrolled and underwent FE-MRV on a 3-Τ MRI system. Two observers assessed FE-MRV images for image quality, signal intensity ratio (SIR), perforator (PV) diameter, and luminal signal uniformity in deep-to-superficial venous networks with the assessment of intra- and inter-rater reliability. FE-MRV was used to detect lower-extremity VVs.
RESULTS: Eleven patients underwent FE-MRV without adverse events. The average image quality, as scored by the two observers who assessed 275 venous segments, was 3.4 ± 0.6. Two observers strongly agreed on image quality (κ = 0.90) and SIR measurements (interclass correlation coefficient [ICC]: 0.72) and had good agreement on PV diameter (ICC: 0.64). FE-MRV revealed uniform luminal signals in deep and saphenous venous networks (0.13 ± 0.05 vs 0.08 ± 0.03). Below-knee segments exhibited a significantly higher heterogeneity index than above-knee (p = 0.039) segments. Superficial VVs were observed in 55% (12/22) of legs in 64% (7/11) of patients. Calf muscle VVs were present in 64% (14/22) of legs in 9 patients.
CONCLUSIONS: FE-MRV safely and robustly mapped entire lower-extremity venous networks, enabling the detection and pre-treatment evaluation of both superficial, and deep VVs in patients with diabetes.
CONCLUSIONS: Ferumoxytol-enhanced magnetic resonance venography offers a \"one-stop\" imaging strategy for the detection and pre-operative evaluation of both superficial and deep VVs in diabetic patients.
CONCLUSIONS: Diabetic patients with VVs are at a higher risk of ulcer-related complications. FE-MRV allowed rapid and comprehensive visualization of the lower-limb venous networks and abdominopelvic veins in diabetic patients. This technique allowed for the detection of superficial and deep VVs in diabetic patients before the development of severe peripheral artery disease.

OBJECTIVE: Lower extremity amputation continues to be necessary in a significant number of patients with peripheral vascular disease. The 5-year survival following lower limb loss is markedly reduced. Many of these patients are never fitted with a prosthesis, and there is a dearth of knowledge regarding the barriers to prosthetic attainment. The goal of this study was to identify the risk factors for not receiving a prosthesis and the effect of mobility level on survival following major amputation.
METHODS: This was a retrospective analysis of all patients that underwent lower extremity amputation by surgeons in our practice from January 1, 2010, to December 31, 2019. Abstracted data included: age, sex, race, body mass index, comorbidities, American Society of Anesthesiologists score, statin use, level of amputation, stump revision, fitting for prosthesis, type of prosthesis, and the United States\' Medicare Functional Classification Level, also called K level. Survival was determined using a combination of sources, including the Social Security Death Master File, searches of multiple genealogic registries, and general internet searches. Multivariable logistic regression was used to determine risk factors associated with prosthesis attainment. Multivariable Cox proportional hazard regression with time-dependent covariates was performed to assess risk factors associated with 5-year mortality.
RESULTS: A total of 464 patients were included in this study. The mean age was 65 years, and mean body mass index was 27 kg/m2. The majority of patients were male (68%), White (56%), diabetic (62%), and hypertensive (76%), and underwent below-the-knee amputation (69%). Prosthetic attainment occurred in 185 (40%). On multivariable analysis, age >81 years and current tobacco use were associated with no prosthetic fitting. Overall 5-year survival was 41.9% (95% confidence interval [CI], 37.6%-46.6%) (below-the-knee amputation, 47.7% [95% CI, 42.5%-53.5%]; above-the-knee amputation, 28.7% [95% CI, 22.1%-37.2%]). On multivariable analysis, age >60 years, congestive heart failure, above-the-knee amputation, and no prosthetic attainment were associated with decreased survival. Increasing K level was incrementally associated with improved survival.
CONCLUSIONS: This study has identified several patient factors associated with prosthetic attainment, as well as multiple factors predictive of reduced survival after amputation. Being referred for prosthetic fitting was associated with improved survival not explained by patient characteristics and comorbidities. The Medicare Functional Classification Level K level predicts survival. More research is needed to determine the barriers to prosthetic attainment and if improving a patients K level will improve survival.

With an aging population, it is common to encounter people diagnosed with peripheral vascular disease (PVD). Some will undergo surgeries during which the spinal cord may be compromised and intraoperative neuromonitoring with motor evoked potentials (MEPs) is employed to help mitigate paralysis. No data exist on characteristics of MEPs in older, PVD patients, which would be valuable for patients undergoing spinal cord at-risk surgery or participating in neurophysiological research. Transcranial magnetic stimulation, which can be delivered to the awake patient, was used to stimulate the motor cortex of 20 patients (mean (±SD)) age 63.2yrs (±11.5) with confirmed PVD, every 10 minutes for one hour with MEPs recorded from selected upper and lower limb muscles. Data were compared to that from 20 healthy volunteers recruited for a protocol development study (28yrs (±7.6)). MEPs did not differ between patient\'s symptomatic and asymptomatic legs. MEP amplitudes were not different for a given muscle between patients and healthy participants. Except for vastus lateralis, disease severity did not correlate with MEP amplitude. There were no differences over time in the coefficient of variation of MEP amplitude at each time point for any muscle in patients or in healthy participants. Although latencies of MEPs were not different between patients and healthy participants for a given muscle, they were longer in older participants. The results obtained suggest PVD alone does not impact MEPs; there were no differences between more symptomatic and less symptomatic legs. Further, in general, disease severity did not corelate with MEP characteristics. With an aging population, more patients with PVD and cardiovascular risk factors will be participating in neurophysiological studies or undergoing surgery where spinal cord integrity is monitored. Our data show that MEPs from these patients can be easily evoked and interpreted.