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OBJECTIVE: Current guidelines recommend dual antiplatelet (AP) therapy (DAPT) before carotid artery stenting (CAS); however, the true clinical effect of single AP therapy vs DAPT is unknown. We examined the efficacy and safety of preoperative single AP therapy vs DAPT in patients who had undergone transfemoral CAS (tfCAS) or transcarotid artery revascularization (TCAR).METHODS: We identified all patients who had undergone tfCAS or TCAR in the Vascular Quality Initiative database from 2016 to 2021. We stratified the patients by procedure and identified those who had received the following preoperative AP regimens: DAPT (acetylsalicylic acid [ASA] + P2Y12 inhibitor [P2Yi]), no AP therapy, ASA only, ASA + AP loading dose, P2Yi only, and P2Yi + AP loading dose. The AP loading dose was given within 4 hours of CAS. We generated propensity scores for each treatment regimen and assessed in-hospital outcomes using inverse probability weighted log binomial regression, with DAPT as the reference and adjusting for intraoperative protamine use. The primary efficacy outcome was a composite end point of stroke and death, and the primary safety outcome was access-related bleeding.RESULTS: Of the 18,570 tfCAS patients, 70% had received DAPT, 5.6% no AP therapy, 10% ASA only, 8.0% ASA + AP loading dose, 4.6% P2Yi only, and 2.9% P2Yi + AP loading dose. The corresponding unadjusted rates of stroke/death were 2.2%, 6.8%, 4.1%, 5.1%, 2.4%, and 2.3%. After adjustment, compared with DAPT, the incidence of stroke/death was higher with no AP therapy (relative risk [RR], 2.3; 95% confidence interval [CI], 1.7-3.2), ASA only (RR, 1.6; 95% CI, 1.2-2.1), and ASA + AP loading dose (RR, 2.0; 95% CI, 1.5-2.7) but was similar with P2Yi only (RR, 0.99; 95% CI, 0.58-1.7) and P2Yi + AP loading dose (RR, 1.1; 95% CI, 0.49-2.5). Of the 25,459 TCAR patients, 81% had received DAPT, 2.0% no AP therapy, 5.5% ASA only, 3.5% ASA + AP loading dose, 4.9% P2Yi only, and 2.4% P2Yi + AP loading dose. The corresponding unadjusted rates of stroke/death were 1.5%, 3.3%, 3.3%, 2.9%, 1.2%, and 1.1%. After adjustment, compared with DAPT, the incidence of stroke/death was higher with no AP therapy (RR, 2.0; 95% CI, 1.2-3.3) and ASA only (RR, 2.2; 95% CI, 1.5-3.1), with a trend toward a higher incidence with ASA + AP loading dose (RR, 1.6; 95% CI, 0.99-2.6), and was similar with P2Yi only (RR, 0.98; 95% CI, 0.54-1.8) and P2Yi + AP loading dose (RR, 0.66; 95% CI, 0.27-1.6). No differences were found in the incidence of access-related bleeding between the treatment groups after tfCAS or TCAR.CONCLUSIONS: Compared with DAPT, no AP therapy or ASA monotherapy was associated with higher rates of stroke/death after CAS and should be discouraged as unsafe practice. Meanwhile, P2Yi monotherapy was associated with similar rates of stroke/death. No differences were found in the incidence of bleeding complications, and adding an AP loading dose to ASA or P2Yi monotherapy within 4 hours of the procedure did not affect the outcomes. Overall, these findings support the current guidelines recommending DAPT before CAS but also suggest that P2Yi monotherapy might confer thromboembolic benefits similar to those with DAPT. However, an immediate preoperative AP loading dose might not provide additional thromboembolic benefits.

ZusammenfassungDie biostatistische Bewertung DNA-analytischer Befunde unterstützt Gerichte bei der Einschätzung des Beweiswertes einer Spur. In der Praxis werden dabei zunehmend Spuren mit minimaler DNA-Menge und möglichen „Drop-in“- und „Drop-out“-Ereignissen sowie komplexe Mischspuren analysiert. Solche Spuren sind mit einer klassischen „binären“ Berechnung biostatistisch häufig nicht oder nur eingeschränkt bewertbar.Die Entwicklung vollkontinuierlicher Modelle (VKM) macht eine Vielzahl dieser bisher nicht berechenbaren Spuren einer biostatistischen Bewertung zugänglich. Dabei werden nahezu sämtliche verfügbaren Informationen einer DNA-Spur in die Berechnung einbezogen. Während diese probabilistischen Verfahren international bereits vielfach zum Einsatz kommen, liegen hierzu im deutschsprachigen Raum nur wenige Erfahrungen vor.Um Funktionsweise, Möglichkeiten und Grenzen von VKM-Berechnungen zu erfassen, wurden Mischspuren bekannter Zusammensetzung mit 4 aktuell verfügbaren VKM-Programmen vergleichend analysiert. Bei der Auswertung wurden zentrale Aspekte betrachtet, wie beispielsweise die Konkordanz von Berechnungsergebnissen, der Einfluss von Drop-in- und Drop-out-Ereignissen auf die berechneten vollkontinuierlichen LR-Werte (LRfc) sowie die Ableitung recherchefähiger DNA-Profile mithilfe wahrscheinlichkeitsbasierter Prognosen (Deconvolution).Die im Rahmen dieser Arbeit gewonnenen Erfahrungen bilden, zusammen mit weiteren bereits international publizierten Studien, eine Basis für Empfehlungen zum Einsatz von VKM-basierter Software bei der biostatistischen Bewertung DNA-analytischer Befunde.

Endovascular treatment of femoropopliteal artery disease has shifted toward drug-coated balloons (DCB). However, limited data are available regarding the safety and efficacy of DCB vs bare-metal stents (BMS).To compare DCB vs BMS outcomes in a propensity-adjusted, pooled analysis of 4 prospective, multicenter trials.Patient-level data were pooled from 4 prospective, multicenter studies: the IN.PACT SFA I/II and IN.PACT SFA Japan randomized controlled DCB trials and the Complete SE and DURABILITY II single-arm BMS studies. Outcomes were compared using inverse probability of treatment weighting (IPTW). Clinical endpoints were 12-month primary patency, freedom from 36-month clinically driven target lesion revascularization, and cumulative 36-month major adverse events (MAE).The primary analysis included 771 patients (288 DCB, 483 BMS). IPTW-adjusted demographic, baseline lesion, and procedural characteristics were matched between groups. The adjusted mean lesion length was 8.1 ± 4.7 cm DCB and 7.9 ± 4.5 cm BMS. The IPTW-adjusted Kaplan-Meier estimates of 12-month primary patency (90.4% DCB, 80.9% BMS, P = 0.007), freedom from 36-month clinically driven target lesion revascularization (85.6% DCB, 73.7% BMS, P = 0.001), and cumulative incidence of 36-month MAE (25.3% DCB, 38.8% BMS, P0.001) favored DCB. There were no statistically significant differences observed in all-cause mortality, target limb major amputation, or thrombosis through 36 months.In a patient-level, IPTW-adjusted pooled analysis of prospective, multicenter pivotal studies, DCB demonstrated significantly higher patency, lower revascularization and MAE rates, and no statistically significant differences in mortality, amputation, or thrombosis versus BMS. This analysis supports DCB use vs BMS in moderately complex femoropopliteal lesions amenable to both treatments.

Patients with chronic limb-threatening ischemia (CLTI) require revascularization to improve limb perfusion and thereby limit the risk of amputation. It is uncertain whether an initial strategy of endovascular therapy or surgical revascularization for CLTI is superior for improving limb outcomes.In this international, randomized trial, we enrolled 1830 patients with CLTI and infrainguinal peripheral artery disease in two parallel-cohort trials. Patients who had a single segment of great saphenous vein that could be used for surgery were assigned to cohort 1. Patients who needed an alternative bypass conduit were assigned to cohort 2. The primary outcome was a composite of a major adverse limb event - which was defined as amputation above the ankle or a major limb reintervention (a new bypass graft or graft revision, thrombectomy, or thrombolysis) - or death from any cause.In cohort 1, after a median follow-up of 2.7 years, a primary-outcome event occurred in 302 of 709 patients (42.6%) in the surgical group and in 408 of 711 patients (57.4%) in the endovascular group (hazard ratio, 0.68; 95% confidence interval [CI], 0.59 to 0.79; P0.001). In cohort 2, a primary-outcome event occurred in 83 of 194 patients (42.8%) in the surgical group and in 95 of 199 patients (47.7%) in the endovascular group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06; P = 0.12) after a median follow-up of 1.6 years. The incidence of adverse events was similar in the two groups in the two cohorts.Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar. (Funded by the National Heart, Lung, and Blood Institute; BEST-CLI ClinicalTrials.gov number, NCT02060630.).

ZusammenfassungDie biostatistische Bewertung DNA-analytischer Befunde unterstützt Gerichte bei der Einschätzung des Beweiswertes hinsichtlich einer möglichen Spurenbeteiligung durch eine zu betrachtende Person (engl. „Person Of Interest“; POI). Um die Vergleichbarkeit derartiger Berechnungen auf Grundlage etablierter wissenschaftlicher Standards zu gewährleisten, wurden bereits in der Vergangenheit entsprechende Empfehlungen im nationalen Konsens formuliert.Mit Einführung sog. vollkontinuierlicher Modelle (VKM) für die probabilistische Genotypisierung, die u. a. die Signalintensitäten eines Elektropherogramms berücksichtigen, wurde eine Ergänzung zu den damaligen Empfehlungen erforderlich. VKM erlauben eine biostatistische Bewertung von Spuren mit möglichen Drop-in- und Drop-out-Ereignissen und wahrscheinlichkeitsbasierte Prognosen der zu einer Mischspur beitragenden Genotypen („Deconvolution“).Die vorliegende Veröffentlichung enthält Empfehlungen zum Einsatz VKM-basierter Software und zur Berichterstattung vollkontinuierlicher LR-Werte (engl. „Fully Continuous Likelihood Ratios“; LRfc). Sie empfiehlt bei schwierig zu interpretierenden Befunden eine VKM-Berechnung zur Bewertung einer Spurenlegerschaft. Die VKM-Berechnung ersetzt die bisher in Ausnahmefällen als hinnehmbar erachtete Vorgehensweise einer binären Berechnung unter Ausklammern einzelner Merkmalssysteme. Der Einsatz von VKM erfordert eine umfassende Anwenderschulung sowie eine Validierung und Verifizierung gemäß den Vorgaben der Programmanbieter. Mit der Empfehlung von LRfc-Schwellenwerten soll eine sichere, vergleichbare Anwendung von VKM gewährleistet werden.

Strategies of balloon dilation during transfemoral carotid artery stenting include prestent dilation only (PRE), post-stent dilation only (POST), or both predilation and postdilation (PRE+POST). Concerns over higher neurological risk have been raised with POST and PRE+POST during transfemoral carotid artery stenting. Whether these concerns are applicable to transcarotid artery revascularization (TCAR), which uses proximal clamping and cerebral blood flow reversal during stent deployment and balloon angioplasty remains unknown. Our aim is to analyze outcomes of PRE, POST, or PRE+POST balloon dilation strategies during TCAR.We analyzed the prospectively collected data from the ROADSTER1 (pivotal), ROADSTER2 (US Food and Drug Administration indicated postmarket), and ROADSTER Extended Access TCAR trials. All trial patients had a high risk anatomic or clinical factors for carotid endarterectomy and were included, unless they did not undergo stent deployment or balloon dilation. For trial inclusion, asymptomatic patients had a carotid stenosis of more than 80%, and symptomatic patients had stenosis of more than 50%. Primary outcome measures were stroke, death, and myocardial infarction (MI) at 30 days. Data were statistically analyzed with χThere were 851 patients (566 male) who underwent dilation by PRE (n = 216), POST (n = 249), or PRE+POST (n = 386). Patients had carotid stenosis of greater than 70% (n = 828, 97%), and 207 (24%) were symptomatic. Flow reversal times were longer in the PRE+POST group (PRE 10.2 minutes, POST 9.8 minutes, and PRE+POST 13.3 minutes; P .001). The 30-day stroke rate for the whole cohort was 1.9%, mortality was 0.5%, and MI rate was 0.94%. Stroke rates for the PRE cohort (1.9%), POST cohort (2.0%), and PRE+POST cohort (1.8%; P = .98) were similar. Also, death rates at 30 days, and composite stroke, death, and MI rates were similar in the three cohorts. No significant differences in adverse outcomes were noted among the various dilation strategies for both symptomatic and asymptomatic patients.Based on these prospective trial data, there is no difference in neurological complications owing to balloon dilation strategy during TCAR. The balloon dilation technique best suited to the patient's specific lesion morphology should be used. Further studies are needed to evaluate the relationship of these dilation strategies to long-term outcomes, including stent patency, restenosis, and reintervention.

The goal of the current review is to examine the hazards and benefits of carotid interventions in women and to provide recommendations for the indications for carotid intervention in female patients. Stroke and cerebrovascular disease are prevalent in women. There are inherent biological and other differences in men and women, which affect the manifestations and outcome of stroke, with women experiencing worse disability and higher mortality following ischemic stroke than men. Due to the underrepresentation of female patients in most clinical trials, the ability to make firm but alternative recommendations for women specifically on the management of carotid stenosis is challenging. Although some data suggest that women might have worse periprocedural outcomes as compared to men following all carotid revascularization procedures, there is also an abundance of data to support a similar risk for carotid procedures in men and women, especially with carotid endarterectomy and transcarotid artery revascularization. Therefore, the indications for carotid revascularization are the same in women as they are in men. The choice of a carotid revascularization procedure in women is based upon the same factors as in men and requires careful evaluation of a particular patient’s risk profile, anatomic criteria, plaque morphology, and medical comorbidities that might favor one technique over the other. When performing carotid revascularization procedures in women, tailored techniques and procedures to address the small diameter of the female artery are warranted.

Sudden cardiac death (SCD) in adolescents and young adults may be the first manifestation of an inherited arrhythmic syndrome. Thus identification of a genetic origin in sudden death cases deemed inconclusive after a comprehensive autopsy and may help to reduce the risk of lethal episodes in the remaining family. Using next-generation sequencing (NGS), a large number of variants of unknown significance (VUS) are detected. In the majority of cases, there is insufficient evidence of pathogenicity, representing a huge dilemma in current genetic investigations. Misinterpretation of such variants may lead to inaccurate genetic diagnoses and/or the adoption of unnecessary and/or inappropriate therapeutic approaches. In our study, we applied current (ACMG) recommendations for variant classification in post-mortem genetic screening of a cohort of 56 SCD victims. We identified a total 53 rare protein-altering variants (MAF

ZusammenfassungMithilfe der Analyse von mRNA-Expressionsmustern durch Einsatz der PCR-Amplifikation von zellspezifischen cDNA-Transkripten und Nachweis der Amplifikate mittels Kapillarelektrophorese (CE) lässt sich die Frage klären, aus welchen Zelltypen (Blut, Speichel, Sperma, Vaginalschleimhaut, Menstrual- und Nasensekret) sich eine biologische Spur zusammensetzt. Durch Verwendung der DNA-RNA-Koextraktion kann dieses Verfahren unabhängig von der STR-Typisierung durchgeführt werden. Am Beispiel des hier dargestellten Falles, bei dem Vaginalsekret der verletzten Frau am Mittelfinger des Beschuldigten nachgewiesen wurde, wird gezeigt, dass der Einsatz dieser Methode besonders bei Fällen von sexualisierter Gewalt sinnvoll ist.

Peripheral arterial disease is an increasingly prevalent condition with significant associated morbidity, mortality, and health care expenditure. Endovascular interventions are appropriate for most patients with either ongoing symptoms of intermittent claudication despite lifestyle and medical optimization or chronic limb-threatening ischemia. The femoropopliteal segment is the most common arterial culprit responsible for claudication and the most commonly revascularized segment. Endovascular approaches to revascularization of the femoropopliteal segment are advancing with an evolving landscape of techniques for arterial access, device-based therapies, vessel preparation, and intraprocedural imaging. These advances have been marked by debate and controversy, notably related to the safety of paclitaxel-based devices and necessity of atherectomy. In this review, we provide a critical overview of the current evidence, practice patterns, emerging evidence, and technological advances for endovascular intervention of the femoropopliteal arterial segment.

ZusammenfassungDie forensische DNA-Analyse hat sich in den letzten Jahrzehnten mit zunehmender Sensitivität und gleichzeitiger Standardisierung der Methodik zu einem festen Bestandteilteil der Strafverfolgung entwickelt. Dank der ständigen Verbesserung der Analysemethoden ist es zwischenzeitlich nahezu selbstverständlich, immer kleinere, latente DNA-Spuren erfolgreich zu typisieren. Dies führt mehr und mehr zu einer Verlagerung der Sachverständigentätigkeit in die Bewertung komplexer Spurenszenarien im Rahmen einer Hauptverhandlung: Anstelle der Zuordnung einer Spur zu einer Person rückt die Spurenentstehung bzw. die Möglichkeit eines DNA-Transfers ohne Bezug zu einer strafrechtlich relevanten Handlung in den Fokus der Diskussion. Aus Sicht der Deutschen Spurenkommission erscheint es notwendig, das Bewusstsein für mögliche alternative Szenarien zur Spurenentstehung zu schärfen. Zur Einordnung eines DNA-Ergebnisses in den Kontext der übrigen Sachbeweise eines konkreten Fallszenarios wird im vorliegenden Beitrag das bereits in der internationalen Fachliteratur seit geraumer Zeit etablierte Konzept der „Hierarchie der Hypothesen“ vorgestellt. Darüber hinaus werden die wissenschaftlichen Grundlagen zur Bewertung alternativer Szenarien des DNA-Transfers erläutert und gleichzeitig die Möglichkeiten und Grenzen einer gutachterlichen Stellungnahme dargestellt.

Objective Patients may be considered at high risk for CEA due to either anatomical or physiologic factors and are often treated with TCAR. Patients with physiologic criteria are deemed to have higher overall surgical risk due to more significant comorbidities. Our aim is to study the incidence of stroke, myocardial infarction (MI), death, and combined endpoints in patients who underwent TCAR comparing ANAT vs. PHYS risk factors. Methods An analysis of the prospectively collected data from the ROADSTER (pivotal), ROADSTER2 (FDA indicated post-market), and ROADSTER Extended Access TCAR trials was performed. All patients (n=851) were considered to be at high risk for CEA and were included and stratified based on high risk ANAT criteria (contralateral occlusion, tandem stenosis, high cervical artery stenosis, restenosis after previous endarterectomy, bilateral carotid stent, hostile neck with previous neck irradiation, neck dissection, or cervical spine immobility) or high-risk PHYS criteria (age75 years, multi-vessel coronary artery disease, history of angina, congestive heart failure NYHA class III/IV, left ventricular ejection fraction30%, recent MI, severe chronic obstructive pulmonary disease (COPD), permanent contralateral cranial nerve injury, or chronic renal insufficiency). For trial inclusion, asymptomatic patients had80% carotid stenosis and symptomatic patients had50% stenosis. Primary outcome measures were stroke, death, and MI at 30 days. Data was statistically analyzed with the χ2 test as appropriate. Results There were 851 high surgical risk patients categorized into ANAT only risk factors (n = 372) or having at least one PHYS risk factor (n = 479). The ANAT subset had 74.5% asymptomatic patients, while the PHYS subset had 76.6%. General anesthesia was employed similarly in both groups (67.7% ANAT vs. 68.1% PHYS). MI occurred in 8 PHYS (1.7%) patients all of whom were asymptomatic and in no ANAT patients (p = .01). Combined stroke, death, and MI rate was 2.1% in the ANAT cohort, compared to 4.2% in the PHYS cohort (p = .10). Stratification of each group into asymptomatic and symptomatic patients did not yield any further differences. Conclusion Patients who underwent TCAR in this prospective, neurologically adjudicated trial based on high-risk PHYS factors had higher rates of MI compared to patients who qualified with ANAT criteria only. These patients experienced comparable rates of combined stroke/death/MI rates. ANAT patients represent a healthier and younger subset of patients, with notably low overall event rates.

The application of 2 distinct and simultaneously applied drug-delivery platforms for the treatment of peripheral artery disease (PAD) has not been studied. This study investigated the outcomes of femoropopliteal disease treated with drug-coated balloon (DCB) followed by placement of drug-eluting stent (DES) when a bail-out procedure is required.This was a single-center, retrospective study enrolling 22 consecutive patients (23 limbs) treated with DCB + DES. Bail-out stenting was performed for flow-limiting postangioplasty dissections and/or suboptimal angiographic result, such as residual stenosis. Procedural success (30% residual stenosis) and the incidence of major adverse limb event (MALE) during an average follow-up of 15.2 months were estimated.Among the 22 patients (23 limbs), 14 presented with claudication and 8 with critical limb ischemia. The majority of the lesions were Trans-Atlantic Inter-Society Consensus class C/D, with a mean lesion length of 321 ± 130 mm. DCB angioplasty was performed with Stellarex (Philips) in 6 cases and In.Pact DCB (Medtronic) in 16 cases. Eluvia DES (Boston Scientific) was used for bail-out stenting in all cases (in 10 limbs for flow-limiting dissection and in 13 limbs for suboptimal angiographic result due to significant residual stenosis and/or recoil). A single Eluvia DES was used in 15 cases, while multiple Eluvia DESs were used in 8 cases. Procedural success was achieved in all but 1 case where persistent recoil occurred in a heavily calcified lesion. During an average follow-up of 15 months, restenosis or reocclusion of the target vessel was observed in 6 cases (26.1%), although only 3 patients required repeat revascularization (13.0%). During follow-up, 1 death and 1 major amputation occurred, both in patients who had originally presented with critical limb ischemia. Additionally, on routine duplex ultrasound, there were no cases of aneurysm formation at the sites of Eluvia stent placement.DCB with provisional DES implantation could be a viable treatment option for cases of suboptimal DCB results, without apparent additional cardiovascular or limb-related risks. Additional studies are needed to determine the risks and benefits of double-dose paclitaxel approach, especially for those patients with significant residual stenosis after DCB.

ZusammenfassungDie quantitative Analyse der relativen DNA-Methylierung gilt als eine der vielversprechendsten Methoden der molekularen Altersschätzung. Viele Studien der letzten Jahre identifizierten geeignete Positionen im Genom, deren DNA-Methylierung sich altersabhängig verändert. Für den Einsatz dieser Methode in der Routine- bzw. Fallarbeit ist es von großer Bedeutung, angewandte Analysetechniken zu validieren. Als ein Teilaspekt dieser Validierung sollte die Vergleichbarkeit der Analyseergebnisse zur DNA-Methylierung mithilfe der Mini- und Pyrosequenzierung zwischen verschiedenen Laboren evaluiert werden. Die Arbeitsgruppe „Molekulare Altersschätzung“ der Deutschen Gesellschaft für Rechtsmedizin (DGRM) führte hierzu den ersten, technischen Ringversuch durch, der 4 Positionen in den Genen PDE4C, EDARADD, SST und KLF14 umfasste. Diese Marker waren in vorangegangenen Studien als altersabhängige Biomarker charakterisiert worden. Am Ringversuch nahmen 12 Labore teil, wobei jedes die Wahl zwischen der Minisequenzierung und/oder der Pyrosequenzierung für die quantitative Methylierungsanalyse hatte. Jedem teilnehmenden Labor wurden Blut- und Speichelproben von 3 Personen unterschiedlichen Alters übersandt. Die Wahl der Reagenzien für die Probenbearbeitung wurde den Teilnehmern freigestellt.Die Ergebnisse der Minisequenzierung zeigten systematische Abweichungen zwischen den Laboren, die am ehesten auf die Verwendung unterschiedlicher Reagenzien und Analyseplattformen zurückzuführen sein können. Die Resultate der Pyrosequenzierung hingegen wiesen nicht auf systematische Abweichungen zwischen den Laboren hin, hier zeigte sich jedoch die Tendenz einer markerabhängigen Abweichung. Darüber hinaus konnten Unterschiede hinsichtlich technischer Probleme zwischen Laboren mit mehr Erfahrung in der jeweiligen Sequenzierungsmethode und Laboren mit weniger Erfahrung festgestellt werden. Sowohl die Beobachtung von systematischen als auch die von markerabhängigen Abweichungen lässt den Schluss zu, dass eine Übertragung von Analysemethoden zwischen Laboren grundsätzlich möglich ist, eine Anpassung des jeweiligen Modells zur Altersschätzung jedoch notwendig sein kann.

Die epigenetische Altersschatzung anhand von DNA-Methylierungsmarkern mithilfe molekulargenetischer Analyseverfahren ist im vergangenen Jahrzehnt intensiv untersucht worden und findet zunehmend Anwendung in der forensischen Routinearbeit, v. a. zur Altersschatzung unbekannter Verursacher von Tatortspuren. Die vorliegende Ubersichtsarbeit soll ein Verstandnis der wissenschaftlichen Grundlagen sowie der praktischen Durchfuhrung der epigenetischen Altersschatzung im Kontext forensischer Routinearbeit vermitteln. Die DNA-Methylierung wird als Biomarker fur das chronologische Alter vorgestellt und die grundlegende Funktionsweise mathematischer Schatzmodelle erklart. Zudem werden die gangigsten Sequenzierungsplattformen zur Methylierungsanalyse erlautert, und es wird auf deren Vor- und Nachteile in Bezug auf die Anwendbarkeit bei forensisch relevantem Probenmaterial eingegangen. Ein weiterer Fokus dieser Ubersichtsarbeit liegt auf der Darstellung der Ergebnisse der epigenetischen Altersschatzung und der Formulierung der Schatzgenauigkeit mit konkreten Vorschlagen fur eine verstandliche Prasentation der Ergebnisse. In Bezug auf die rechtlichen Grundlagen der Anwendung der epigenetischen Altersschatzung wird deutlich gemacht, dass damit keine genetisch festgeschriebenen individualisierenden Eigenschaften einer Person offengelegt werden und diese somit den konventionellen medizinisch-diagnostischen Analysen zugeordnet werden kann.

The SVS Wound, Ischemia, foot Infection (WIfI) limb staging system was established to estimate risk of major amputation in chronic limb-threatening ischemia (CLTI) and better stratify outcomes comparisons. There is little data on treatment outcomes beyond one year based on presenting WIfI stage.This is a single-institution retrospective study of 413 patients who underwent infrainguinal revascularization for CLTI (2011-2021) with data available for WIfI staging. Patient characteristics and outcomes were gathered from the electronic medical record. Data were analyzed based on presenting WIfI stage and initial treatment received at our center.Presenting WIfI stages were 1-2 (23%), 3 (27%) and 4 (50%). Index revascularization approach was endoluminal (59%), autogenous vein bypass (29%), or non-autogenous bypass (13%). Operative mortality within 30 days was 2.9% and was not associated with WIfI stage or revascularization approach. Median limb follow-up time was 502 days (IQR 112-1256), and median survival follow-up time was 932 days (IQR 343-1770). Major amputation or death occurred in 19% and 46% of patients at median times of 119 days (IQR 28-314) and 739 days (IQR 204-1475), respectively. WIfI stage was independently associated with major amputation (p=0.001), as was initial revascularization approach (p=0.01). In a Cox proportional hazards model, factors independently associated with major amputation were male sex [HR 1.4 (1.04-2.0), p=0.03], diabetes [HR1.8 (1.3-2.5), p=0.001], WIfI stage 4 [HR 2.3 (1.5-3.5), p0.001], and non-autogenous bypass [HR 2.9 (2.1-4.2) p0.001]. In a Cox proportional hazards model for mortality, independently associated factors were age [HR 1.04 (1.02-1.05), p0.001], ESRD [HR 2.8 (1.9-4.0), p0.001], CHF [HR 1.9 (1.4-2.5), p0.001], COPD [HR 1.5 (1.1-2.1, p=0.02), and WIfI stage 4 [HR 1.6 (1.04-2.2), p=0.03]. Among those presenting with WIfI stage 4 limbs, Kaplan-Meier estimated rates of freedom from major amputation or death at 2 years were 71% ± 3.7% and 68% ± 3.5%, respectively. In an inverse propensity weighted Cox proportional hazards model, non-white race [HR 1.5 (1.01-2.2), p=0.047], diabetes [HR 2.0 (1.2-3.3), p=0.008], GLASS IP grade [HR 1.2 (1.05-1.3), p=0.005], non-autogenous bypass [HR 3.2 (1.9-5.3), p0.001], and endoluminal revascularization [HR 2.6 (1.6-4.3), p0.001] were independently associated with major amputation in the WIfI stage 4 subgroup.Presenting WIfI stage is strongly associated with long-term risks of major amputation and death following infrainguinal revascularization for CLTI and should be used to stratify outcomes comparisons. Effective revascularization is critical in WIfI stage 4 disease, and autogenous vein bypass provides durable long-term limb preservation.

Despite the shared pathogenesis of peripheral arterial disease (PAD) and vascular dementia, there is little data on cognitive impairment in PAD patients. We hypothesized that cognitive impairment will be common and previously unrecognized.Cognitive impairment screening was prospectively performed for Veterans presenting to a single Veterans Affairs outpatient vascular surgery clinic from 2020-2021 for PAD consultation or disease surveillance. Overall, 125 Veterans were screened. Cognitive impairment was defined as a score of26 on the Montreal Cognitive Assessment (MoCA) survey. A multivariable logistic regression assessed for independent risk factors for cognitive impairment.Overall, 77 (61%) had cognitive impairment, 92% was previously unrecognized. Cognitive impairment was associated with increased age (74.4 vs. 71.8 years, p=0.03), Black vs. White race (94% vs. 54%, p0.01), hypertension (66% vs. 31%, p=0.01), prior stroke/TIA (79% vs. 58%, p=0.03), diabetes treated with insulin (79% vs. 58%, p=0.05), and post-traumatic stress disorder (PTSD) (80% vs. 57%, p=0.04). On multivariable analysis, risk factors for newly diagnosed cognitive impairment included age ≥ 70 years, diabetes treated with insulin, PTSD, and Black race.Many Veterans with PAD have evidence of cognitive impairment and is overwhelmingly underdiagnosed. This study suggests cognitive impairment is an unrecognized issue in a VA population with PAD, requiring more study to determine cognitive impairment's impact on surgical outcomes, and how it can be mitigated and incorporated into clinical care.

DNA methylation has become one of the most useful biomarkers for age prediction and body fluid identification in the forensic field. Therefore, several assays have been developed to detect age-associated and body fluid-specific DNA methylation changes. Among the many methods developed, SNaPshot-based assays should be particularly useful in forensic laboratories, as they permit multiplex analysis and use the same capillary electrophoresis instrumentation as STR analysis. However, technical validation of any developed assays is crucial for their proper integration into routine forensic workflow. In the present collaborative exercise, two SNaPshot multiplex assays for age prediction and a SNaPshot multiplex for body fluid identification were tested in twelve laboratories. The experimental set-up of the exercise was designed to reflect the entire workflow of SNaPshot-based methylation analysis and involved four increasingly complex tasks designed to detect potential factors influencing methylation measurements. The results of body fluid identification from each laboratory provided sufficient information to determine appropriate age prediction methods in subsequent analysis. In age prediction, systematic measurement differences resulting from the type of genetic analyzer used were identified as the biggest cause of DNA methylation variation between laboratories. Also, the use of a buffer that ensures a high ratio of specific to non-specific primer binding resulted in changes in DNA methylation measurement, especially when using degenerate primers in the PCR reaction. In addition, high input volumes of bisulfite-converted DNA often caused PCR failure, presumably due to carry-over of PCR inhibitors from the bisulfite conversion reaction. The proficiency of the analysts and experimental conditions for efficient SNaPshot reactions were also important for consistent DNA methylation measurement. Several bisulfite conversion kits were used for this study, but differences resulting from the use of any specific kit were not clearly discerned. Even when different experimental settings were used in each laboratory, a positive outcome of the study was a mean absolute age prediction error amongst participant's data of only 2.7 years for semen, 5.0 years for blood and 3.8 years for saliva.

The estimation of the chronological age based on DNA methylation markers by bisulfite sequencing is a promising new method in forensic molecular genetics. The application of the method to forensic trace samples from crime scenes was recently legalized following a change of the German law. Biological traces display a challenging sample source since they are usually of small amount. To increase sensitivity, we have developed an optimized pyrosequencing protocol for quantitative methylation analysis.

Background: Transforming Growth Factor-b1 (TGF-b1) is a genetic modifier in patients with cystic fibrosis (CF). Several single nucleotide polymorphisms (SNPs) of TGF-b1 are associated with neutrophilic inflammation, lung fibrosis und loss of pulmonary function. Aim: The aim of this study was to assess the relationship between genetic TGF-b1 polymorphisms and pulmonary disease progression in CF patients. Furthermore, the effect of TGF-b1 polymorphisms on inflammatory cytokines in sputum were investigated. Methods: 56 CF-patients and 62 controls were genotyped for three relevant SNPs in their TGF-b1 sequence using the SNaPshot® technique. Individual “slopes” in forced expiratory volume in 1 second (FEV1) for all patients were calculated by using documented lung function values of the previous five years. The status of Pseudomonas aeruginosa (Pa) infection was determined. Sputum concentrations of the protease elastase, the serine protease inhibitor elafin and the cytokines IL-1b, IL-8, IL-6, TNF-α were measured after a standardized sputum induction and processing. Results: The homozygous TT genotype at codon 10 was associated with a lower rate of chronic Pa infection (p Higher levels of TGF-b1 in plasma were associated with a more rapid FEV1 decline over five years (pConclusions: Our results suggest that polymorphisms in the TGF-b1 gene have an effect on lung function decline, Pa infection as well as levels of inflammatory cytokines. Genotyping these polymorphisms could potentially be used to identify CF patients with higher risk of disease progression. TGF-b1 inhibition could potentially be developed as a new therapeutic option to modulate CF lung disease.

In 2019, the Global Vascular Guidelines on chronic limb-threatening ischemia (CLTI) introduced the concept of limb-based patency (LBP) defined as maintained patency of a target artery pathway after intervention. The purpose of this study was to investigate the relationship between LBP and major adverse limb events (MALE) after infrainguinal revascularization for CLTI.Consecutive patients undergoing revascularization for CLTI between 2016 and 2019 at a single tertiary institution with a dedicated limb preservation team were included. Subjects with aortoiliac disease, prior infrainguinal stents, or existing bypass grafts were excluded. Demographics, Global Limb Anatomic Staging System scores, Wound, Ischemia, foot Infection (WIfI) stages, revascularization details, and limb-specific outcomes were reviewed. LBP was defined by the absence of reintervention, occlusion, critical stenosis (70%), or hemodynamic compromise with ongoing symptoms of CLTI. MALE included thrombectomy or thrombolysis, new bypass, open surgical graft revision and/or major amputation.We analyzed 184 unique limbs in 163 patients. This cohort was composed of 66.9% male patients with a mean age of 72 years. Baseline characteristics included diabetes (66%), tissue loss (91%), and advanced WIfI stages (30% stage 3, 51% stage 4). Global Limb Anatomic Staging System stage 3 anatomic patterns were common (n = 119 [65%]). Sixty limbs were treated with open bypass (65% involving tibial targets) and 124 underwent endovascular intervention (70% including infrapopliteal targets). The 12-month freedom from MALE and loss of LBP were 74.0% ± 3.7% and 48.6% ± 4.2%, respectively. Diabetes (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.13-5.83; P = .025) and loss of LBP (HR, 4.12; 95% CI, 1.96-8.64; P .001) were independent predictors of MALE in a Cox proportional hazard model. Loss of LBP was the sole independent predictor of major limb amputation after revascularization (HR, 4.97; 95% CI, 1.89-13.09; P = .001). Loss of LBP impacted both intermediate-risk limbs (HR, 2.85; 95% CI, 1.02-7.97; P = .047 in WIfI stages 1-3) and high-risk limbs (HR, 3.99; 95% CI, 1.32-12.11; P = .014 in WIfI stage 4). However, the loss of LBP had the greatest impact on patients presenting with WIfI stage 4 disease (31% vs 8% major limb amputation at 12 months in limbs without vs with maintained LBP).The anatomic durability of revascularization, as measured by LBP, is a key determinant of treatment outcomes in CLTI regardless of the initial mode of intervention undertaken. Loss of LBP is most detrimental in patients presenting with advanced limb threat (WIfI stage 4).

Pedal medial arterial calcification (pMAC) is associated with major amputation in patients with chronic limb-threatening ischemia (CLTI). We hypothesize that this association would be related to unresolved distal ischemia. We investigated relationships across pMAC score, hemodynamic change, and major amputation after infrainguinal revascularization for CLTI.This is a single-institution, retrospective study of 306 patients who underwent technically successful infrainguinal revascularization for CLTI (2011-2020) and had foot x-rays for blinded pMAC scoring (0-5). A total of 136 (44%) patients had toe pressure measurements performed within 90 days before and 60 days after revascularization. Ischemia grade (0-3) was assigned using the Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) system.The revascularization approach was open bypass in 118 (38%) and endovascular in 188 (62%) patients. pMAC scores were trichotomized (0-1 [125; 41%], 2-4 [116; 38%], 5 [65; 21%]). Post-revascularization WIfI ischemia grade was improved in 78 of 136 (57%) and unchanged/worsened in 58 of 136 (43%). A lower pMAC score was associated with hemodynamic improvement (P = .004). Failure to improve the ischemia grade was associated with major amputation (P = .0002). In the endovascular subgroup, WIfI ischemia grade was improved in 43 of 90 (48%) with available measurements, and 37 of 188 (20%) underwent major amputation. In a multivariate logistic model, pMAC 5 was the only factor independently associated with unimproved ischemia grade after endovascular treatment (odds ratio: 4.0 [1.1-16.6], P = .04). In a Cox proportional hazards model, factors independently associated with major amputation after endoluminal revascularization were WIfI stage 4 (hazard ratio [HR]: 2.7 [1.3-5.7], P = .007) and pMAC score (pMAC: 2-4: HR: 10.6 [1.4-80.7], P = .02; pMAC: 5: HR: 15.5 [2.0-119], P = .008). In the bypass subgroup, WIfI ischemia grade was improved in 35 of 46 (76%) with available measurements but was not associated with pMAC score (P = .88) or any other baseline patient or limb characteristics. A total of 19 of 118 (16%) patients underwent major amputation. In a Cox proportional hazards model including bypass conduit, WIfI stage, and pMAC score, the only factor independently associated with major amputation after bypass was use of nonautologous conduit (HR: 5.6 [1.8-17.6], P = .003).The pMAC score is independently associated with persistent distal ischemia and major amputation after technically successful revascularization for CLTI. These data suggest that pMAC may be a marker for hemodynamic response to revascularization and risk of limb loss, and it may have a stronger influence on the outcome of endoluminal interventions.

Although the benefits of carotid endarterectomy (CEA) for treating symptomatic carotid stenosis are well known, the optimal timing of intervention after acute stroke and whether the optimal timing will vary with preoperative stroke severity has remained unclear. Therefore, we assessed the effect of stroke severity and timing of the intervention on the postoperative outcomes for patients who had undergone CEA for stroke.We identified all patients in the Vascular Quality Initiative who had undergone CEA from 2012 to 2020 for prior stroke. The patients were stratified using the preoperative modified Rankin scale score (mRS score, 0-5) and time to CEA after stroke onset (≤2 days, 3-14 days, 15-90 days, 91-180 days). After univariate comparisons, the patients were stratified into the following mRS cohorts for further analysis: 0 to 1, 2, 3 to 4, and 5. The primary outcome was in-hospital stroke/death.We identified 15,601 patients, of whom 30% had had an mRS score of 0, 34% an mRS score of 1, 17% an mRS score of 2, 11% an mRS score of 3, 8% an mRS score of 4, and 1% an mRS score of 5. Overall, 9.3% of the patients had undergone CEA within ≤2 days, 46% within 3 to 14 days, 36% in 15 to 90 days, and 8.4% within 90 to 180 days. A decreasing mRS score and an increasing time to CEA were associated with lower rates of perioperative stroke/death (PPatients with minimal disability after stroke (mRS score, 0-1) seemed to benefit from CEA within 3 to 14 days. However, those with severe disability (mRS score 5) have a very high risk from CEA at any time point given the poor outcomes. In contrast to the current guidelines, patients with mild disability (mRS score 2) could benefit from delaying CEA to 15 to 90 days, and those with moderate disability (mRS score 3-4) might benefit from CEA within 3 to 90 days given the acceptable in-hospital outcomes. These data should be considered within the context of the clinical situation in the weeks after index event to determine the net benefit of delayed CEA.

Transcarotid artery revascularization (TCAR) is a carotid stenting technique that utilizes reversal of cerebral arterial flow to confer cerebral protection. Although carotid endarterectomy (CEA) remains the standard for treatment of symptomatic and asymptomatic carotid stenosis, the search for the optimal minimally invasive option for the high-risk surgical patient continues. The goal of the current study is to evaluate the 1-year safety and efficacy of TCAR in a prospective clinical trial.ROADSTER 2 is a prospective, open-label, single-arm, multicenter, post-approval registry for patients undergoing TCAR. All patients were considered high risk for CEA and underwent independent neurological assessments preoperatively, postoperatively, and had long-term clinical follow-up. The primary end point was incidence of ipsilateral stroke after treatment with the ENROUTE Transcarotid Stent System. Secondary end points included individual/composite rates of stroke, death, and perioperative myocardial infarction.Between June 2016 and November 2018, 155 patients at 21 centers in the United States and one in the European Union were enrolled and represented a subset of the overall trial. Asymptomatic (n = 119; 77%) and symptomatic patients (n = 36; 23%) with high-risk anatomic (ie, high lesion, restenosis, radiation injury; 43%), physiologic (32%), or combined factors (25%) were enrolled. No patient suffered a perioperative myocardial infarction or stroke. Over the year, no patient had an ipsilateral stroke, but four patients died (2.6%), all from non-neurological causes. Additionally, a technical success rate of 98.7% with a low cranial nerve deficit rate of 1.3% was achieved.In patients with high risk factors, TCAR yields high technical success with a low stroke and death rate at 1 year. Further comparative studies with CEA are warranted.

Sudden cardiac death (SCD) in adolescents and young adults may be the first manifestation of an inherited arrhythmic syndrome. Thus identification of a genetic origin in sudden death cases deemed inconclusive after a comprehensive autopsy and may help to reduce the risk of lethal episodes in the remaining family. Using next-generation sequencing (NGS), a large number of variants of unknown significance (VUS) are detected. In the majority of cases, there is insufficient evidence of pathogenicity, representing a huge dilemma in current genetic investigations. Misinterpretation of such variants may lead to inaccurate genetic diagnoses and/or the adoption of unnecessary and/or inappropriate therapeutic approaches. In our study, we applied current (ACMG) recommendations for variant classification in post-mortem genetic screening of a cohort of 56 SCD victims. We identified a total 53 rare protein-altering variants (MAF 0.2%) classified as VUS or worse. Twelve percent of the cases exhibited a clinically actionable variant (pathogenic, likely pathogenic or VUS - potentially pathogenic) that would warrant cascade genetic screening in relatives. Most of the variants detected by means of the post-mortem genetic investigations were VUS. Thus, genetic testing by itself might be fairly meaningless without supporting background data. This data reinforces the need for an experienced multidisciplinary team for obtaining reliable and accountable interpretations of variant significance for elucidating potential causes for SCDs in the young. This enables the early identification of relatives at risk or excludes family members as genetic carriers. Also, development of adequate forensic guidelines to enable appropriate interpretation of rare genetic variants is fundamental.

The monumental district of Florence/Italy and the workers’ quarter Kiel-Gaarden/Germany are two case studies on the use of mapping for storyscapes on different levels. Architectural heritage is most commonly understood to be representable and representative of a nation, city or cultural group. Not only in the aftermath of armed confrontation, is a re-assessment of what should be considered worthy of preservation and remembrance necessary, but it becomes perhaps a matter of every generation to re-evaluate of what matters in the built environment as part of an identity-shaping process. Part of this on-going process could be coming to terms with the historic past, and to include the forgotten aspects and events, which had shaped to some extent the lives of a group of people, communities or entire nations. In heritage studies, this contested heritage is known for instance as “shared heritage”, “uncomfortable heritage”, and places may be even described as “traumascapes”.3 What is known as the “spatial turn” occurred roughly 20 years ago.4 It is employed in the humanities where cartographic maps become a methodological tool. It is not a new approach to understand the historic context through space and in space, but it has undergone a re-launch because mass data can be processed and linked to a GIS. When this data becomes available online, transand interdisciplinary research is facilitated with a possibility to open up new perspectives and research fields. Especially in the area of architectural heritage, a field still largely dominated by expertism, this method may act as an inclusive and democratic tool for communities, which are not yet an integral part of a heritage discourse. It also provides an opportunity to integrate new heritage topics and places to be – if not preserved so at least – remembered. By visualizing for instance an urban space and the different places with a variety of functions and events, links between them can be revealed, which otherwise would have gone unnoticed. What has been termed in this context a “deep map” is “a finely detailed, multimedia depiction of place and the people, animals, and objects that exist within it, and are thus inseparable from the contours and rhythms of everyday life. Deep maps are not confined to the tangible or material, but include the discursive and ideological dimensions of place, the dreams, hopes, and fears of residents – they are, in short, positioned between matter and meanings. […] It is simultaneously a platform, a process, and a product. It is an environment embedded with tools to bring data into an explicit and direct relationship with space and time.”5 The relationship between space and human activity is well reflected in sociology stating that “space cannot be […] distinguished from society, but it is a specific form of society. Spatial structures are, just like temporal structures, forms of social structures”.6 That means that space and human activity constitute elements of heritage. At the same time, digitalisation has a decisive impact on the possibility for accessing primary data, for creating maps with this data, and to share these maps. Two case studies will demonstrate here how the map-based reconstruction of spatial activity helps to reveal different approaches to social realities. The case studies examine very different places and situations and will illustrate the potential of deep mapping to generate attention for hitherto neglected facets of life in urban spaces.

© 2019 The Authors Current forensic ancestry-informative panels are limited in their ability to differentiate populations in the Asia-Pacific region. MAPlex (Multiplex for the Asia-Pacific), a massively parallel sequencing (MPS) assay, was developed to improve differentiation of East Asian, South Asian and Near Oceanian populations found in the extensive cross-continental Asian region that shows complex patterns of admixture at its margins. This study reports the development of MAPlex; the selection of SNPs in combination with microhaplotype markers; assay design considerations for reducing the lengths of microhaplotypes while preserving their ancestry-informativeness; adoption of new population-informative multiple-allele SNPs; compilation of South Asian-informative SNPs suitable for forensic AIMs panels; and the compilation of extensive reference and test population genotypes from online whole-genome-sequence data for MAPlex markers. STRUCTURE genetic clustering software was used to gauge the ability of MAPlex to differentiate a broad set of populations from South and East Asia, the West Pacific regions of Near Oceania, as well as the other globally distributed population groups. Preliminary assessment of MAPlex indicates enhanced South Asian differentiation with increased divergence between West Eurasian, South Asian and East Asian populations, compared to previous forensic SNP panels of comparable scale. In addition, MAPlex shows efficient differentiation of Middle Eastern individuals from Europeans. MAPlex is the first forensic AIM assay to combine binary and multiple-allele SNPs with microhaplotypes, adding the potential to detect and analyze mixed source forensic DNA.

Patients undergoing revascularization for chronic limb-threatening ischemia (CLTI) are at elevated risk for both mortality and limb loss. To facilitate therapeutic decision-making, a mortality prediction model derived from the Vascular Quality Initiative (VQI) database has stratified patients into low, medium, and high risk, defined by 30-day mortality estimates of ≤3%, 3%-5%, or5% and 2-year mortality estimates of ≤30%, 30%-50%, or ≥50%, respectively. The purpose of this study was to compare expected mortality risk derived from this model with observed outcomes in a tertiary center.Consecutive patients treated at a single center between 2016 and 2019 were analyzed. Baseline demographics, approach, and mortality events were reviewed. Observed mortality was obtained using life-table methods and compared using a log-rank test with the expected mortality risk that was calculated using the VQI model.This study cohort consisted of 195 revascularization procedures in 169 unique patients stratified into 128 (66%) low-, 50 (26%) medium-, and 17 (8%) high-risk cases based on the VQI model. Ninety percent of revascularizations were performed for tissue loss. Compared with the VQI population, comorbidities were prevalent and included unstable angina or myocardial infarction within 6 months (6% vs 2.4% in VQI; P .001), congestive heart failure (30% vs 23%; P .001), and dialysis dependence (14% vs 0.9%; P .001). Patients were also older (31% vs 21% ≥80 years old; P .001) and more likely to be frail (45% vs 64% independent; P .001). High-risk patients were more prevalent in the endovascular group (11% of 132 endovascular interventions vs 3% of 63 bypasses; P = .056). Thirty-day observed mortality exceeded expected VQI prediction model mortality in all groups, although was not statistically significant. The VQI model adequately stratified the studied population into risk groups (P .001). Low-risk patients with CLTI (65% of the overall cohort) experienced 2-year mortality of 18.9%. However, observed mortality rates for medium- and high-risk VQI strata were similar. After a median follow-up of 28 months, medium-risk patients incurred a significantly higher mortality than predicted (53.5% ± 2.1% vs 36.8% ± 1.1%; P = .016).The VQI mortality prediction model discriminates mortality risk after limb revascularization in CLTI, accurately identifying a majority subgroup of patients who are suitable for either open or endovascular intervention. However, it may underestimate mortality in a tertiary referral population with high comorbidity burden and was not well calibrated for the medium-risk group. It may be more appropriate to dichotomize patients with CLTI who are candidates for limb salvage into an average-risk and high-risk group.