Tissue Loss Research Articles

Competing risk analysis to estimate amputation incidence and risk in lower-extremity peripheral artery disease.

Background: Patients with peripheral artery disease face high amputation and mortality risk. When assessing vascular outcomes, consideration of mortality as a competing risk is not routine. We hypothesize standard time-to-event methods will overestimate major amputation risk in chronic limb-threatening ischemia (CLTI) and non-CLTI. Methods: Patients undergoing peripheral vascular intervention from 2017 to 2018 were abstracted from the Vascular Quality Initiative registry and stratified by mean age (⩾ 75 vs < 75 years). Mortality and amputation data were obtained from Medicare claims. The 2-year cumulative incidence function (CIF) and risk of major amputation from standard time-to-event analysis (1 - Kaplan-Meier and Cox regression) were compared with competing risk analysis (Aalen-Johansen and Fine-Gray model) in CLTI and non-CLTI. Results: A total of 7273 patients with CLTI and 5095 with non-CLTI were included. At 2-year follow up, 13.1% of patients underwent major amputation and 33.4% died without major amputation in the CLTI cohort; 1.3% and 10.7%, respectively, in the non-CLTI cohort. In CLTI, standard time-to-event analysis overestimated the 2-year CIF of major amputation by 20.5% and 13.7%, respectively, in patients ⩾ 75 and < 75 years old compared with competing risk analysis. The standard Cox regression overestimated adjusted 2-year major amputation risk in patients ⩾ 75 versus < 75 years old by 7.0%. In non-CLTI, the CIF was overestimated by 7.1% in patients ⩾ 75 years, and the adjusted risk was overestimated by 5.1% compared with competing risk analysis. Conclusions: Standard time-to-event analysis overestimates the incidence and risk of major amputation, especially in CLTI. Competing risk analyses are alternative approaches to estimate accurately amputation risk in vascular outcomes research.

Streamlined Clinical Management Pathways May Reduce Major Amputations in Patients with Chronic Limb Threatening Ischaemia: A Prospective Cohort Study with Historical Controls

Patient characteristics and patterns of disease in chronic limb threatening ischaemia (CLTI) have changed markedly in recent years. Urgent specialist referral and timely revascularisation are recommended in international guidelines. UK guidelines now recommend revascularisation within 5 days of referral for inpatients and 2 weeks in outpatients. This study compared the contemporary one year major amputation incidence in patients with CLTI with a historical cohort at a single UK centre. This was a single centre, observational cohort study with historical controls. A prospective cohort was recruited between May 2019 and March 2022. A historical cohort presenting between 2013 and 2015 inclusive was identified retrospectively. Significant changes in management pathways, including establishing a rapid access limb salvage clinic, occurred between these periods aiming to expedite time from referral to revascularisation. The one year primary outcome was major amputation, and the secondary outcome was death. Major amputation was analysed by Fine-Gray competing risks models (death as the competing risk), presented as subdistribution hazard ratios (SHRs). One year mortality was analysed by Cox regression, presented as hazard ratios. Analyses were adjusted for propensity score. A total of 928 patients were included (432 prospective and 496 historical). Proportions of patients presenting with tissue loss (72.2% vs. 71.6%; p = .090) were similar in both cohorts. At one year, 48 patients (11.1%) in the prospective cohort and 124 patients (25.0%) in the historical cohort had undergone a major amputation (p < .001). Risk of major amputation was 57.0% lower in the prospective cohort compared with the historical cohort after adjustment for propensity score (SHR 0.43, 95% confidence interval 0.29 - 0.63; p < .001). An encouraging reduction in major amputation incidence was observed after improvements to CLTI management pathways, but residual confounding is likely. The generalisability of these results is uncertain.

Allogenic Vertebral Body Adherent Mesenchymal Stromal Cells Promote Muscle Recovery in Diabetic Mouse Model of Limb Ischemia

Chronic limb threatening ischemia (CLTI) carries a significant risk for amputation especially in diabetic patients with poor options for revascularization. Phase I trials have demonstrated efficacy of allogeneic mesenchymal stromal cells (MSC) in treating diabetic CLTI. Vertebral bone adherent mesenchymal stromal cells (vBA-MSC) are derived from vertebral bodies of deceased organ donors which offer the distinct advantage of providing a 1,000x greater yield compared to that of living donor bone aspiration. This study describes the effects of intramuscular injection of allogenic vBA-MSC in promoting limb perfusion and muscle recovery in a diabetic CLTI mouse model. A CLTI mouse model was created through unilateral ligation of the femoral artery in male polygenic diabetic TALLYHO mice. Treated mice were injected with vBA-MSC into the gracilis muscle of the ischemic limb 7 days post ligation. Gastrocnemius or tibialis muscle was assessed post-mortem for fibrosis by collagen staining, capillary density via immunohistochemistry, and mRNA by quantitative real time PCR. Laser Doppler perfusion imaging and plantar flexion muscle testing were performed to quantify changes in limb perfusion and muscle function. Compared to vehicle control, treated mice demonstrated indicators of muscle recovery including decreased fibrosis, increased perfusion, muscle torque, and angiogenesis. PCR analysis of muscle obtained 7- and 30-days post vBA-MSC injection showed an upregulation in expression of MyoD1 (p = 0.03) and MyH3 (p = 0.008) mRNA representing muscle regeneration, VEGF-A (p = 0.002 ; p = 0.004) signifying angiogenesis as well as IL-10 (p < 0.001), T regulatory cell marker Foxp3 (p = 0.04), and M2-biased macrophage marker Mrc1 (CD206) (p = 0.02). These findings indicate human allogeneic vBA-MSC ameliorate ischemic muscle damage and rescue muscle function. These results in a murine model will enable further studies to develop potential therapies for diabetic CLTI patients.

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers are Associated with Improved Amputation Free Survival in Chronic Limb-Threatening Ischemia

BackgroundIn the Heart Outcomes Prevention Evaluation (HOPE) study, investigators found that ramipril was associated with improved survival as well as decreased MI and stroke rates in patients with peripheral arterial disease. Nonetheless, their effect on chronic limb-threatening ischemia (CLTI)-specific outcomes is unclear. We aim to assess the effect of ACEIs/ARBs on amputation-free survival in CLTI patients undergoing peripheral vascular intervention (PVI) in a Medicare-linked database. MethodsPatients undergoing PVI in the VQI-VISION database were included. Primary outcome included amputation-free survival. Kaplan Meier survival and multivariable Cox regression analyses were used to assess one-year outcomes. ResultsA total of 34,284 patients were included, and 46.3% of whom were discharged on ACEIs/ARBs. Patients discharged on ACEIs/ARBs were more likely to be smokers, diabetics, and hypertensive. They were also more likely to present with rest pain. The overall one-year survival for patients on ACEIs/ARBs vs those who are not was (79.1% vs 69.4%, P<0.001). Freedom from amputation was 87.8% for patients on ACEIs/ARBs vs 84.2% for those who were not (P<0.001). Amputation-free survival was 70.5% vs 59.5% for ACEIs/ARBs vs no ACEIs/ARBs (P<0.001). After adjusting for potential confounders, ACEIs/ARBs use was associated with lower one-year mortality (HR: 0.77, 95%CI (0.7-0.8), P<0.001), amputation (HR: 0.89, 95%CI (0.8-0.9), P<0.001), and amputation or death (HR: 0.79, 95%CI (0.76-0.8), P<0.001). ConclusionsACEIs/ARBs were independently associated with lower amputation, improved survival, and amputation-free survival at one year in CLTI patients undergoing PVI. The fact that more than half the patients were not discharged on these medications presents an area for potential quality improvement.

Hemoglobin A1c levels are related to patency and adverse limb events in diabetics after revascularization

ObjectivePoor glycemic control in the perioperative period has been reported to be associated with early and late major adverse limb events (MALEs). However, these studies were mostly from large databases or lacked long-term outcomes. We examined the long-term effects of high hemoglobin A1c (HbA1c) level on patency, MALE, limb salvage (LS) and survival after lower extremity revascularization procedures in patients with diabetes. MethodsPatients with diabetes who underwent revascularization for Rutherford class 3 to 6 ischemia between May 2002 and December 2018 were identified. Patients with an HbA1c of ≤7% were compared with those with an HbA1c of >7% for patency, MALE, survival, LS, and amputation-free survival. ResultsOf 706 patients, 699 had HbA1c data (775 limbs), with 311 (357 limbs) in the HbA1c ≤7% and 388 (418 limbs) in the HbA1c >7% groups. Patients with an HbA1c of >7% were younger (69.9 ± 10.2 years vs 71.7 ± 9.5 years; P = .011), had higher lipid levels, insulin use (70% vs 49%; P < .01), American Society of Anesthesiologists classification of 4, and had a lower prevalence of chronic kidney disease (32% v s41%; P = .023). Patients with an HbA1c of >7% were more likely to present with chronic limb-threatening ischemia (CLTI) (79% vs 72%; P = .019) and undergo infrapopliteal interventions (49% vs 42%; P = .005), with no difference in anatomical complexity (TransAtlantic Inter Society Consensus class C/D, 75% vs 77%; P = .72) or type of revascularization (24% vs 18% open, 66% vs 70% endovascular, 10% vs 12% hybrid; P = .236). Patency and freedom from MALE were significantly lower in patients with an HbA1c of >7% for infrainguinal revascularizations, whereas amputation-free survival and overall survival were similar. In patients with chronic limb-threatening ischemia, LS rates at 5 years were significantly lower in patients undergoing open revascularization (HbA1c > 7%: 64% ± 6% vs HbA1c < 7%:86% ± 5%; P = .020), whereas it was similar after endovascular interventions (HbA1c > 7%:79% ± 4% vs HbA1c < 7%:77% ± 3%; P = .631). Seventy patients with an HbA1c of >7% lost limbs vs 38 patients with an HbA1c of ≤7% (P = .007). In multivariate analysis, HbA1c was associated significantly with primary patency. HbA1c, insulin use, level of intervention, and angiotensin-converting enzyme inhibitor use were associated with MALE. ConclusionsA perioperative HbA1c of >7% is associated with poorer patency rates and increased MALE, especially at the infrainguinal level revascularization in patients with diabetes, with no significant impact on survival. LS is impacted after open, but not after endovascular revascularization.

Prosthetic conduits have worse outcomes compared with great saphenous vein conduits in femoropopliteal and infrapopliteal bypass in patients with chronic limb-threatening ischemia

ObjectiveSingle segment great saphenous vein (SSGSV) traditionally has been considered the gold standard conduit for infrainguinal bypass. There are data supporting similar outcomes with prosthetic femoral-popliteal bypass. Moreover, some investigators have advocated for prosthetic conduit for femoral tibial bypass when GSV is inadequate or unavailable. We sought to evaluate long-term outcomes of infrainguinal bypass based on conduit type for treating chronic limb-threatening ischemia (CLTI). MethodsData from the Best Endovascular vs Best Surgical Therapy of Patients with CLTI multicenter, prospective, randomized controlled trial, comparing infrainguinal bypass with endovascular therapy in patients with CLTI, were evaluated. In this as-treated analysis, we compared outcomes of infrainguinal bypass using prosthetic, alternative autogenous vein (AAV), and cryopreserved vein (Cryo) with SSGSV bypass. Kaplan-Meier and multivariable analyses were performed to examine the associations of conduit type with major adverse limb events (MALE), reinterventions, above-ankle amputations, and all-cause death rates. ResultsIn total, 784 bypasses were analyzed (120 prosthetic, 33 AAV, 21 Cryo, AND 610 SSGSV). For prosthetic and SSGSV, the distribution was 357 femoropopliteal (93 prosthetic and 264 GSV) and 373 infrapopliteal (27 prosthetic and 346 GSV). The mean age for the overall cohort was 67.1 years; 27.4% were female, 29.9% were non-White, and 11.5% were of Hispanic ethnicity. Patients undergoing prosthetic bypass were older (69.2 years vs 66.7 years); more likely to have chronic obstructive pulmonary disease (22.5% vs 14.0%), prior coronary artery bypass grafting (88.9% vs 66.5%), and prior stroke (23.3% vs 14%); but less often were of Hispanic ethnicity (5.8% vs 12.6%) and had diabetes (59.2% vs 71.3%) (P < .05 for all). For femoropopliteal bypass, use of prosthetic conduit was associated with increased major reinterventions at 3 years overall (19.0% vs 11.5%; P = .06) and on risk-adjusted analysis (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.09-4.2; P = .028). No significant differences in MALE or death, above-ankle amputation, or death were observed. Outcomes were similar for bypasses to above-knee popliteal targets and below-knee popliteal targets. For infrapopliteal bypass, the use of a prosthetic conduit was associated with increased major reintervention (25.3% vs 10.3%; P = .005), death (68.6% vs 34.8%; P < .001), and MALE or death (90.0% vs 48.1%; P < .001) at 3 years. After risk adjustment, infrapopliteal bypass with prosthetic conduit was associated with higher major reintervention (HR, 4.14; 95% CI, 1.36-12.6; P = .012), above-ankle amputation (HR, 4.64; 95% CI, 1.59-13.5; P = .005), death (HR, 2.96; 95% CI, 1.4-6.2; P = .004), and MALE or death (HR, 3.59; 95% CI, 1.64-7.86; P = .001) compared with bypass with SSGSV. Overall, AAV had similar outcomes at 3 years as SSGSV; however, Cryo had significantly higher above-ankle amputation (50.0% vs 12.8%) (HR, 4.2; 95% CI, 1.68-10.5; P = .002), major reintervention (41.9% vs 10.7%) (HR, 3.12; 95% CI, 1.18-8.22; P = .02), and MALE/death (88.8% vs 37.8%) (HR, 2.96; 95% CI, 1.43-6.14; P = .004). ConclusionsThe use of a prosthetic conduit in infrainguinal bypass is associated with inferior outcomes compared with bypass using SSGSV, particularly for bypass to infrapopliteal targets. Cryo grafts were infrequent and also demonstrated inferior outcomes. SSGSV remains the preferred conduit of choice for infrainguinal bypass.

Patients with dementia or frailty undergoing major limb amputation have poor outcomes

ObjectiveMajor lower limb amputation is a disfiguring operation associated with impaired mobility and high near-term mortality. Informed decision-making regarding amputation requires outcomes data. Despite the co-occurrence of both chronic limb-threatening ischemia (CLTI) and Alzheimer’s disease and related dementias (ADRD), there is sparse data on the outcomes of major limb amputation in this population and the impact of frailty. We sought to determine mortality, complications, readmissions, revisions, intensive interventions (eg, cardiopulmonary resuscitation), and other outcomes after amputation for CLTI in patients living with ADRD looking at the modifying effects of frailty. MethodsWe examined Medicare fee-for-service claims data from January 1, 2016, to December 31, 2020. Patients with CLTI undergoing amputation at or proximal to the ankle were included. Along with demographic information, dementia status, and comorbid conditions, we measured frailty using a claims-based frailty index. We dichotomized dementia and frailty (pre-frail/robust = “non-frail” vs moderate/severe frailty = “frail”) to create four groups: non-frail/non-ADRD, frail/non-ADRD, non-frail/ADRD, and frail/ADRD. We used linear and logistic regression via generalized estimating equations in addition to performing selected outcomes analyses with death as a competing risk to understand the association between dementia status, frailty status, and 1-year mortality as our primary outcome in addition to the postoperative outcomes outlined above. ResultsAmong 46,930 patients undergoing major limb amputation, 11,465 (24.4%) had ADRD and 24,790 (52.8%) had frailty. Overall, 55.9% of amputations were below-knee. Selected outcomes among frail/ADRD patients undergoing amputation (n = 10,153) were: 55.3% 1-year mortality 29.6% readmissions at 30 days, and 32.3% amputation revision/reoperation within 1 year. Of all four groups, those in the frail/ADRD had the worst outcomes only for 1-year mortality. ConclusionsFirst, patients with ADRD or moderate/severe frailty suffer an array of very poor outcomes after major limb amputation for CLTI, including high mortality, readmissions, revision, and risks of discharge to higher levels of care. Second, there is a complex relationship between outcome severity and ADRD/frailty status. Specifically, frailty is more often than ADRD associated with the poorest results for any given outcome. These data provide important outcomes data to help align decision-making with health care values and goals.

Comparative Outcomes of Targeted Versus Nontargeted Angiosome Revascularization for Diabetic Foot Wounds Impact of Target Arterial Path on Wound Healing

Diabetes is strongly correlated with the development of critical limb ischemia (CLI), with a predilection for below-the-knee and below-the-ankle patterns of arterial disease. The angiosome concept, described as a potential framework for targeted revascularization in CLI, has generated divergent opinions over the last decades. This study aims to evaluate the implication of angiosome targeted revascularization in wound healing in diabetic patients. This is a single-center retrospective study including diabetic patients with ischemic ulcers admitted for invasive vascular study and revascularization between January and December 2019. The primary outcome was to evaluate the impact of angiosome-targeted revascularization in wound healing. Limb-based patency and amputation-free survival according to GLASS stage and revascularization procedures were considered secondary outcomes. Data from 117 limbs of 114 diabetic patients with neuroischemic diabetic foot were evaluated. There was no significant difference between targeted and non-targeted angiosome-revascularization in wound healing at 12 months. However, angiosome targeted revascularization was associated with shorter healing times. The severity of the infection was the only variable with an impact on healing time. Endovascular surgery did not show inferior patency to open surgery, even in patients with more complex arterial disease (GLASS III). Although angiosome-guided revascularization did not demonstrate significantly higher healing rates at 12 months, there appears to be a trend towards faster healing.

Comparison of Duplex Ultrasound and Digital Subtraction Angiography for Assessing Tibial Vessel Disease.

Background Duplex ultrasonography (DUS) is readily available and often used as the first diagnostic test for patients with peripheral artery diseases (PADs). PAD is a disease that affects the general population but more commonly affects diabetics.To date, the role of DUS in the assessment of tibial vessel disease is inconclusive at best. The goal of our study is to assess the validity of DUS in characterizing the presence and severity of tibial diseasesvia comparison with digital subtraction angiography (DSA) findings. Methods This is a single-center retrospective cohort study analyzing three arterial segments (anterior tibial, posterior tibial, and fibular arteries) in patients who received a duplex study followed by DSA within a 30-day period. All arterial segments were graded from normal (Grade 0) to occluded (Grade 4), based on duplex interpretationand directly compared to direct visualization findings from DSA. Using statistical methods, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of DUS were determined. Results A total of 171 tibial vessel segments from 57 enrolled subjects with critical limb ischemia symptoms were analyzed in this study. The agreement between both modalities was poor (Kappa=0.19, p < 0.05), with DUS demonstrating a significant underestimation of vessel pathologies. This is also reflected by the overall sub-optimal sensitivity (23%), specificity (84%), PPV (69%), and NPV (41%) in DUS when compared to DSA results as the gold standard. Conclusion Significant disagreements were noted in this study between DUS and DSA findings, primarilysignificant underestimation of tibial vessel disease by the DUS when compared with the DSA. Caution is advised in the clinical application of DUS in patients with chronic limb-threatening ischemia (CLTI) symptoms and multi-segment tibial vessels due to its demonstrated limitations in this study.

Drug-eluting devices for lower limb peripheral arterial disease.

Peripheral arterial disease is the third leading cause of cardiovascular morbidity after coronary artery disease and stroke. Lower limb peripheral arterial disease commonly involves infrainguinal arteries, may impair walking ability (intermittent claudication) and may confer a significant risk of limb loss (chronic limb-threatening ischaemia), depending on the severity of ischaemia. Endovascular treatment has become the mainstay revascularisation option in both the femoropopliteal and the below-the-knee arterial segments. After crossing and preparing the lesion, treatment results in these arterial segments can be enhanced by using drug-coated devices (drug-eluting stents and drug-coated balloons) that mitigate the occurrence of restenosis. As for other medical devices, the use of drug-eluting devices is based on their demonstrated safety and efficacy profiles when applied in the distinct segments of the lower limb vasculature. In this state-of-the-art narrative review we provide an overview of the safety and efficacy of drug-coated devices when used in the femoropopliteal and below-the-knee arterial segments.

Trends in the utilization of drug-eluting stents to treat femoropopliteal peripheral artery disease

ObjectiveThere is a paucity of data exploring the real-world use of the two drug-eluting stents approved for use in the United States for the treatment of femoropopliteal peripheral artery disease. This study examined the use trends of Eluvia drug-eluting vascular stent and Zilver PTX drug-eluting peripheral stent between 2016 and 2022 using medical claims. MethodsUsing the Truveta data platform, patients aged ≥18 years with peripheral artery disease who underwent lower extremity femoropopliteal peripheral artery endovascular revascularization with either Eluvia paclitaxel-eluting stents (introduced in 2018) or Zilver PTX paclitaxel-coated stents were identified between January 1, 2016, and December 31, 2022. The annual use overall by setting (inpatient vs outpatient) and within clinical subgroups were explored. ResultsOverall, 710 patients who received paclitaxel-eluting stents and 620 who received paclitaxel-coated stents were identified. The paclitaxel-eluting stent was released during the study period; by the end of the study period, paclitaxel-eluting stents accounted for 82% of the index femoropopliteal peripheral artery procedures. The use of paclitaxel-coated stents decreased from 100% to 18% over the same period. This change occurred among patients with diabetes, chronic limb-threatening ischemia, and chronic kidney disease. There were significant differences in stent use by race and geographic region. ConclusionsThe use of paclitaxel-eluting stent for the treatment of femoropopliteal peripheral artery disease in the United States has increased steadily since its introduction in 2018; by 2022, it was used in 82% of femoropopliteal peripheral artery procedures in medical centers using the Truveta platform.

The impact of diabetes mellitus on the outcomes of revascularization for chronic limb-threatening ischemia in the BEST-CLI trial

ObjectiveSeveral observational studies have demonstrated an association between diabetes mellitus (DM) and above-ankle amputation after lower extremity revascularization (LER). However, data from prospective randomized trials is lacking. This analysis compares the outcomes of patients with and without DM enrolled in the Best Endovascular vs Best Surgical Therapy in patients with Chronic Limb-Threatening Ischemia (BEST-CLI) trial. MethodsBaseline characteristics were compared between patients with and without DM in the BEST-CLI trial. Cox regression was used to determine the association between DM and major outcomes of major adverse limb events (MALE), reintervention, above-ankle amputation, and all-cause death. ResultsAmong 1777 patients who underwent LER, 69.2% had DM. Compared with patients without DM, those with DM were significantly younger, less likely to be White, and more likely to be Hispanic. Patients with DM were more likely to have hypertension, hyperlipidemia, coronary artery disease, congestive heart failure, and renal disease and be on optimal medical therapy (antiplatelets and statins), whereas patients without DM were significantly more likely to be smokers and have chronic obstructive pulmonary disease. Patients with DM were significantly more likely to present with late Wound Ischemia foot Infection (WIfI) stages (3-4) (73.7% vs 45.9%; P < .001) that were driven predominantly by differences in wound and infection grade. Conversely, patients without DM had significantly lower ankle pressures and toe pressures and were significantly more likely to have WIfI ischemia grade 3 compared with patients with DM (60% vs 52.5%; P = .016). At 3 years, patients with DM exhibited higher rates of above-ankle amputation and all-cause death compared with patients without DM. Kaplan-Meier analysis demonstrated significantly higher MALE or all-cause death compared with patients without DM (3-year estimate: 53.5% vs 46.4%; P < .001). After adjusting for potential confounders, regression analysis demonstrated that DM was independently associated with increased above-ankle amputation (1.75 [1.22-2.51]), all-cause death (1.63 [1.31-2.03]), and MALE or all-cause death (1.24 [1.04-1.47]). ConclusionsPatients with DM undergoing LER for chronic limb-threatening ischemia experienced a greater incidence of MALE or all-cause death compared with patients without DM. The impact of DM seems to be mediated by more severe wounds and infections at the time of presentation, and a higher prevalence of cardiac and renal disease.

Elevated Composite Inflammatory Markers are Associated with Clinical Severity and Long-term Amputation Risk in Patients with Critical Limb Ischemia after Percutaneous Transluminal Angioplasty

Elevated Composite Inflammatory Markers are Associated with Clinical Severity and Long-term Amputation Risk in Patients with Critical Limb Ischemia after Percutaneous Transluminal Angioplasty

Evaluation Recovery of Ulcerative Colitis with a Lactobacillus Cocktail Derived from Traditional Dairy Products: In vivo Study.

This investigation investigates the anti-inflammatory and fibrinolytic effects of a cocktail of probiotics derived from traditional dairy products in a murine model of ulcerative colitis (UC). A mix of newly isolated probiotics containing L. plantarum, L. brevis, L. delbrueckii, and L. helveticus was characterized and orally administered to inbred eight-week-old C57BL/6 male mice (n = 6). Clinical symptoms, pathohistological changes, and inflammatory and fibrosis markers were analyzed in the existence and absence of probiotics in colitis mice. Dairy lactobacillus probiotics potently attenuated colitis symptoms by decreasing dextran sulfate sodium (DSS)-induced body weight loss, colon shortening, rectal bleeding, and rectal prolapse. Consistently, a cocktail of probiotics could significantly improve histopathological grading by suppressing crypt loss, mucosal damage, and inflammation scores in colitis tissues. Moreover, the mix of probiotics suppressed pro-inflammatory genes including interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), and increased anti-oxidant markers and activity such as superoxide dismutase and catalase in colon tissue. Furthermore, compared to the no-treated group, the administration of probiotics reduced fibrosis by decreasing collagen deposition in tissue sections and down-regulating levels of pro-fibrotic genes including alpha-actin-2 (Acta2), collagen (Col) 1a1, and Col 1a2 in colitis tissue homogenates. The results show the newly isolated cocktail of probiotics elicits a potent protective effect on UC symptoms in mice model. Further study on these probiotics is required to fully explore their effectiveness, strength, and safety considerations.

The effect of intra-articular autologous protein solution on knee osteoarthritis symptoms.

Knee osteoarthritis (OA) is characterized by a chronic inflammatory process involving multiple cytokine pathways, leading to articular cartilage degeneration. Intra-articular therapies using pharmaceutical or autologous anti-inflammatory factors offer potential non-surgical treatment options. Autologous protein solution (APS) is one such product that uses the patient's blood to produce a concentrate of cells and anti-inflammatory cytokines. This study evaluated the effect of a specific APS intra-articular injection (nSTRIDE) on patient-reported outcome measures compared to saline in moderate knee OA. A parallel, double-blinded, placebo-controlled randomized controlled trial was conducted, where patients with unilateral moderate knee OA (Kellgren-Lawrence grade 2 or 3) received either nSTRIDE or saline (placebo) injection to their symptomatic knee. The primary outcome was the difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12 months post-intervention. Secondary outcomes included WOMAC component scores, Knee injury and Osteoarthritis Outcome Score (KOOS), and visual analogue scale (VAS) scores at all follow-up timepoints (three, six, and 12 months). A total of 40 patients were analyzed (21 nSTRIDE; 19 saline) in the study. No significant difference was found between nSTRIDE and saline groups for WOMAC total score at 12 months (mean difference -10.4 (95% CI -24.4 to 3.6; p = 0.141). There were no significant differences in WOMAC or KOOS scores across all timepoints. VAS scores favoured the saline group for both rest and worst pain scales at 12 months post-injection (mean difference (worst) 12 months 21.5 (95% CI 6.2 to 36.8; p = 0.008); mean difference (rest) 12 months 17.8 (95% CI 2.2 to 33.4; p = 0.026)). There were no adverse events recorded in either study group. Our study demonstrates no significant differences between nSTRIDE and saline groups in KOOS and WOMAC scores over time. Notably, APS injection resulted in significantly worse pain symptoms at 12 months compared to saline injection.

Efficacy of Novel Low-Density Lipoprotein Apheresis for Chronic Limb-Threatening Ischemia

Efficacy of Novel Low-Density Lipoprotein Apheresis for Chronic Limb-Threatening Ischemia

Race and the treatment of in-stent restenosis of the femoral-popliteal artery with paclitaxel drug-coated balloon angioplasty

ObjectiveThe aim of this study was to report the impact of race on paclitaxel drug-coated balloon (DCB) angioplasty for the treatment of femoral-popliteal artery in-stent restenosis (ISR). MethodsA prospective, non-randomized, post-market study of a paclitaxel DCB for the treatment of ISR of femoral-popliteal artery was conducted at 43 sites within the Vascular Quality Initiative (December 2016-January 2020). The primary endpoint was freedom from target lesion revascularization (F-TLR) through 12 months. Secondary endpoints included freedom from target vessel revascularization (F-TVR), freedom from major limb amputation, and survival. In this sub-analysis, the results were stratified by self-identified Black vs White race. ResultsBlack patients (n = 63) had a lower mean age (64.3 ± 9.7 vs 68.2 ± 9.7 years; P = .006) and were more often female (57.1% vs 37.0%; P = .004) compared with White patients (n = 219). Most patients had claudication (80.9%), with Black patients presenting with a higher rate of ischemic rest pain (30.2% vs 16.0%; P = .012). By Kaplan-Meier estimates, F-TLR was 91.3% vs 89.1% (log-rank P = .63) and 66.4% vs 74.0% (log-rank P = .41) at 12 and 24 months for Black vs White race. F-TVR was 87.8% vs 87.6% (log-rank P = .96) and 61.3% vs 70.6% (log-rank P = .29) at 12 and 24 months for Black vs White race. Freedom from major target limb amputation was 100.0% vs 99.5% (log-rank P = .59) and 100.0% vs 99.0% (log-rank P = .45) at 12 and 24 months for Black vs White race. Survival was 93.7% vs 95.9% (log-rank P = .47) and 84.1% vs 91.3% (log-rank P = .11) at 12 and 24 months for Black vs White race. In multivariable analysis, no significant predictors were identified for TLR or TVR through 24- months. Dialysis (hazard ratio [HR], 27.69; 95% confidence interval [CI], 10.35-74.09; P < .001), coronary disease (HR, 2.80; 95% CI, 1.29-6.06; P = .009), and lesion length (HR, 1.04; 95% CI, 1.02-1.07; P = .001) were associated with increased mortality through 24 months. Race was not significantly associated with TLR, TVR, or mortality. ConclusionsIn this sub-analysis of a Vascular Quality Initiative-based study, the treatment of femoral-popliteal ISR with paclitaxel angioplasty was equally safe and effective for Black and White races. The trend in reduced survival for patients of Black race at 2 years requires longer observation in a larger study.

The Lateral Antebrachial Neurocutaneous Flap: Case Series.

The neurocutaneous flap was developed based on the understanding that every superficial cutaneous nerve includes vessels, also known as vasa nervorum or paraneural vessels, which run around and inside the nerves and deliver blood to the skin above. A cutaneous perforator connected to paraneural vessels that vascularize the skin and nerves is referred to as a neurocutaneous perforator. The lateral antebrachial cutaneous nerve (LACN), the most dependable blood supply from the primary underlying veins of the neurocutaneous flap, is the subject of this study. We reviewed the results of 30 flap coverage procedures in 10 children. The applied flap was based distally along the radial aspect of the hand and wrist. The pivot point of the flap was located dorsally. This study considered patients with posttraumatic tissue loss, vital structure exposure, or hand contractures with an LACN flap. There was a case-by-case assessment. Thirteen male patients were included; their ages ranged from 6 to 65 years. Demographic data, preoperative cause of trauma, and postoperative complications were collected. Statistically significant improvements were observed after flap healing. The LACN flap is a more versatile flap with less morbidity than other alternative flaps for coverage of soft tissue defect restoration around the hand, wrist, and distal forearm.

Monitoring of myocardial injury by serial measurements of QRS area and T area: The MaastrICCht cohort.

Manually derived electrocardiographic (ECG) parameters were not associated with mortality in mechanically ventilated COVID-19 patients in earlier studies, while increased high-sensitivity cardiac troponin-T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were. To provide evidence for vectorcardiography (VCG) measures as potential cardiac monitoring tool, we investigated VCG trajectories during critical illness. All mechanically ventilated COVID-19 patients were included in the Maastricht Intensive Care Covid Cohort between March 2020 and October 2021. Serum hs-cTnT and NT-proBNP concentrations were measured daily. Conversion of daily 12-lead ECGs to VCGs by a MATLAB-based script provided QRS area, T area, maximal QRS amplitude, and QRS duration. Linear mixed-effect models investigated trajectories in serum and VCG markers over time between non-survivors and survivors, adjusted for confounders. In 322 patients, 5461 hs-cTnT, 5435 NT-proBNP concentrations and 3280 ECGs and VCGs were analyzed. Non-survivors had higher hs-cTnT concentrations at intubation and both hs-cTnT and NT-proBNP significantly increased compared with survivors. In non-survivors, the following VCG parameters decreased more when compared to survivors: QRS area (-0.27 (95% CI) (-0.37 to -0.16, p < .01) μVs per day), T area (-0.39 (-0.62 to -0.16, p < .01) μVs per day), and maximal QRS amplitude (-0.01 (-0.01 to -0.01, p < .01) mV per day). QRS duration did not differ. VCG-derived QRS area and T area decreased in non-survivors compared with survivors, suggesting that an increase in myocardial damage and tissue loss play a role in the course of critical illness and may drive mortality. These VCG markers may be used to monitor critically ill patients.

The Mcgregor Pedicled Groin Flap for Hand Skin Defects

The groin flap is a surgical method used to cover soft tissue defects in the hand and forearm, such as wounds, traumatic amputations, degloving injuries, burns, burn scar release, and tumor excision. It is effective in covering extensive and intricate defects, such as wounds, traumatic amputations, degloving injuries, burns, burn scar release, and tumor excision. The procedure involves a remote autoplasty supported by the vascular territory of the superficial iliac circumflex artery. The flap's boundaries are defined using the "2 fingers width" criterion, and the flap is raised from lateral to medial, transferring subcutaneous tissue while keeping it above the fascia. The flap is closed using drain suction, and the patient is allowed to walk on the 5th day after surgery. Effective preoperative planning is essential for preventing the creation of too big or too tiny flaps and ensuring the fabrication of appropriate tubing to avoid complications. The McGregor groin flap is a commonly used technique for hand deformity reconstruction due to its extended pedicle and quick execution. It is adaptable, repeatable, and can be performed by less-experienced surgeons without microsurgery expertise. The flap covers significant tissue loss with pliable tissue, making it suitable for joints. It can cover abnormalities on the back or palm, and can be used for early wrist and hand rehabilitation. However, it has drawbacks, such as shoulder stiffness in older patients, discomfort during the upper limb positioning, and the need for multiple phases. Despite these, the groin flap remains relevant in the age of microsurgery and can be improved with technical modifications.