Can Ischemia-Modified Albumin Be a Helpful Marker in the Diagnosis and Follow-Up of Childhood Intussusception?

OBJECTIVES: Intussusception is the invagination of a proximal segment of the intestine into a more distal segment. The present study aimed to determine the sensitivity of the ischemia-modified albumin (IMA) and the correlation between IMA and the severity of intestinal ischemia in intussusception cases. METHODS: Thirty-six consecutive children aged between 0 and 16 years presenting with the clinical and radiological features of intestinal obstruction caused by intussusception were enrolled in the study. The age- and sex-matched control group was composed of patients undergoing outpatient surgery. The patients were categorized as cases of type I (ileoileal), type II (ileocecal), and type III (colocolic) based on the ultrasonography findings. RESULTS: The mean IMA level of the intussusception group was 179.13 ± 220.33 ng/mL, whereas the mean level was found as 89 ± 70.9 ng/mL in the control group. When the patients were categorized as ileoileal, ileocecal, and colocolic, the mean IMA levels were detected as 235.65 ± 268.14 ng/mL, 174.46 ± 212.8 ng/mL, and 46.95 ± 19.56 ng/mL, respectively. There was a moderate correlation between the invaginated segment lengths measured by the surgeon during the operation and IMA levels. CONCLUSIONS: Our study findings reveal that IMA can be used as an auxiliary diagnostic marker in patients presenting with symptoms and signs suggestive of intussusception. Thus, patients can be screened for mechanical bowel obstruction due to intussusception and may be referred to pediatric surgery centers earlier for further examination.

COVID-19 and acute limb ischemia: a systematic review.

INTRODUCTION: The main goal of this systematic review was to analyze the outcomes of acute limb ischemia (ALI) in patients suffering from the novel Coronavirus: COVID-19 (SARS-CoV-2). EVIDENCE ACQUISITION: A systematic review on Medline and Embase was conducted up to May 15, 2021. All papers were sorted by abstract and full text by two independent authors. Systematic reviews, commentaries, and studies that did not distinguish status of COVID-19 infection were excluded from review. Patient demographics were recorded along with modality of treatment (endovascular and/or surgical). We analyzed 30-day outcomes, including mortality. Primary outcome was to evaluate clinical characteristic of ALI in patients affected by SARS-CoV-2 in term of location of ischemia, treatment options and 30-day outcomes. EVINDENCE SYNTHESIS: We selected 36 articles with a total of 194 patients. Most patients were male (80%) with a median age of 60 years old. The treatment most used was thromboembolectomy (31% of all surgical interventions). A total of 32 patients (19%) were not submitted to revascularization due to critical status. The rate of technical success was low (68%), and mortality rate was high (35%). CONCLUSIONS: This review confirms that SARS-CoV-2 is associated with a high risk of ALI. Further studies are needed to investigate the association and elucidate potential mechanisms, which may include a hypercoagulable state and hyperactivation of the immune response. Furthermore, management of ALI is not standardized and depends on patient condition and extension of the thrombosed segment. ALI in COVID-19 patients is associated with high risk of failure of revascularization and perioperative mortality.

Effects of chemerin and homocysteine levels and their associations with occurrence and development of ischemic cerebrovascular disease.

BACKGROUND: The current study was conducted to explore the effects of chemerin and homocysteine (Hcy) levels and their associations with the occurrence and development of ischemic cerebrovascular disease (ICVD). METHODS: There involved a total of 187 patients with ICVD and 190 healthy people for physical examination in Cangzhou Central hospital from January 2020 to April 2021. The participants enrolled were divided into four groups based on the digital subtraction angiography: mild stenosis group (64 cases, stenosis rate 30-49 %), moderate stenosis group (72 cases, stenosis rate 50-69 %), severe stenosis group (51 cases, stenosis rate 70-99 %) and control group (190 cases, in healthy condition). The laboratory indexes of ICVD group and control group were observed and the four groups were further compared. Pearson linear correlation was applied to analyze the link between chemerin and Hcy levels and the degree of cerebral vascular stenosis in ICVD patients, and multivariate logistic regression was used to analyze the influencing factors of ICVD. RESULTS: No significant difference was found in general information including age, gender, body mass index (BMI), heart rate, systolic blood pressure, diastolic blood pressure, smoking and drinking between the two groups (P > 0.05). Moreover, there was no significant difference in fasting blood glucose (FBG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels between the two groups (P > 0.05). However, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), chemerin and Hcy in ICVD group were significantly higher than those in control group (P < 0.05). When comparing the four groups, there was no significant difference in FBG and TC levels (P > 0.05). The levels of TG, LDL-C, chemerin and Hcy in mild, moderate and severe stenosis groups were higher than those in control group, the above levels in moderate and severe stenosis group were higher than those in mild stenosis group, and severe stenosis group higher than moderate stenosis group (P < 0.05). Chemerin and Hcy levels were positively correlated with the degree of cerebral vascular stenosis in ICVD patients (r = 0.612, 0.519, P < 0.001). ICVD was regarded as the dependent variable, and the abovementioned general data as well as significant laboratory indicators, including TG, LDL-C, chemerin and Hcy, as independent variables. The results of multivariate logistic regression analysis revealed that TG, LDL-C, chemerin and Hcy were independent influencing factors of ICVD. CONCLUSIONS: Chemerin and Hcy levels exerted a close link to the occurrence and development of ICVD as independent influencing factors.

Adverse Effect of Circadian Rhythm Disorder on Reparative Angiogenesis in Hind Limb Ischemia.

Background Circadian rhythm disorders, often seen in modern lifestyles, are a major social health concern. The aim of this study was to examine whether circadian rhythm disorders would influence angiogenesis and blood perfusion recovery in a mouse model of hind limb ischemia. Methods and Results A jet-lag model was established in C57BL/6J mice using a light-controlled isolation box. Control mice were kept at a light/dark 12:12 (12-hour light and 12-hour dark) condition. Concentrations of plasma vascular endothelial growth factor and circulating endothelial progenitor cells in control mice formed a circadian rhythm, which was diminished in the jet-lag model (P<0.05). The jet-lag condition deteriorated tissue capillary formation (P<0.001) and tissue blood perfusion recovery (P<0.01) in hind limb ischemia, which was associated with downregulation of vascular endothelial growth factor expression in local ischemic tissue and in the plasma. Although the expression of clock genes (ie, Clock, Bmal1, and Cry) in local tissues was upregulated after ischemic injury, the expression levels of cryptochrome (Cry) 1 and Cry2 were inhibited by the jet-lag condition. Next, Cry1 and Cry2 double-knockout mice were examined for blood perfusion recoveries and a reparative angiogenesis. Cry1 and Cry2 double-knockout mice revealed suppressed capillary density (P<0.001) and suppressed tissue blood perfusion recovery (P<0.05) in the hind limb ischemia model. Moreover, knockdown of CRY1/2 in human umbilical vein endothelial cells was accompanied by increased expression of WEE1 and decreased expression of HOXC5. This was associated with decreased proliferative capacity, migration ability, and tube formation ability of human umbilical vein endothelial cells, respectively, leading to impairment of angiogenesis. Conclusions Our data suggest that circadian rhythm disorder deteriorates reparative ischemia-induced angiogenesis and that maintenance of circadian rhythm plays an important role in angiogenesis.

Hippo-YAP/MCP-1 mediated tubular maladaptive repair promote inflammation in renal failed recovery after ischemic AKI.

Acute kidney injury (AKI) is associated with significant morbidity and its chronic inflammation contributes to subsequent chronic kidney disease (CKD) development. Yes-associated protein (YAP), the major transcriptional coactivator of the Hippo pathway, has been shown associated with chronic inflammation, but its role and mechanism in AKI-CKD transition remain unclear. Here we aimed to investigate the role of YAP in AKI-induced chronic inflammation. Renal ischemia/reperfusion (I/R) was used to induce a mouse model of AKI-CKD transition. We used verteporfin (VP), a pharmacological inhibitor of YAP, to treat post-IRI mice for a period, and evaluated the influence of YAP inhibition on long-term outcomes of AKI. In our results, severe IRI led to maladaptive tubular repair, macrophages infiltration, and progressive fibrosis. Following AKI, the Hippo pathway was found significantly altered with YAP persistent activation. Besides, tubular YAP activation was associated with the maladaptive repair, also correlated with interstitial macrophage infiltration. Monocyte chemoattractant protein 1 (MCP-1) was found notably upregulated with YAP activation. Of note, pharmacological inhibition of YAP in vivo attenuated renal inflammation, including macrophage infiltration and MCP-1 overexpression. Consistently, in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) induced YAP activation and MCP-1 overproduction whereas these could be inhibited by VP. In addition, we modulated YAP activity by RNA interference, which further confirmed YAP activation enhances MCP-1 expression. Together, we concluded tubular YAP activation with maladaptive repair exacerbates renal inflammation probably via promoting MCP-1 production, which contributes to AKI-CKD transition.

Pre-operative Neutrophil to Lymphocyte Ratio is Associated With 30 Day Death or Amputation After Revascularisation for Acute Limb Ischaemia.

OBJECTIVE: Inflammation is an early feature of acute limb ischaemia (ALI), hence the potential prognostic significance of inflammatory biomarkers. This study aimed to assess the value of pre-operative inflammatory biomarkers, specifically the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR), for predicting an adverse outcome after revascularisation for ALI. METHODS: All patients submitted to lower limb revascularisation for Rutherford IIa or IIb ALI at the authors' institution between 2009 and 2019 were screened retrospectively. Pre-operative NLR and PLR were analysed, along with other known prognostic factors. Primary outcome was the composite endpoint of 30 day death or amputation. RESULTS: A total of 345 patients were included, 84 of whom suffered the primary outcome (24.3%). The median follow up was 23.1 months (3.1 - 52.2). Higher age (OR 1.05 per year increase, 95% CI 1.01 - 1.09), diabetes (OR 2.63, 95% CI 1.14 - 6.06), Rutherford grade IIb vs. IIa (OR 5.51, 95% CI 2.11 - 14.42), higher NLR (OR 1.28 per unit increase, 95% CI 1.12 - 1.47), and fasciotomy need (OR 3.44, 95% CI 1.14 - 10.34) were independently associated with 30 day death or amputation, whereas pre-operative statin or anticoagulant medication were associated with a risk reduction (OR 0.23, 95% CI 0.53 - 0.96 and OR 0.20, 95% CI 0.05 - 0.84, respectively). PLR did not show an independent effect on this population. Pre-operative NLR presented a good discriminative ability (AUC 0.86, 95% CI 0.82 - 0.90). A cut off NLR level ≥ 5.4 demonstrated a 90.5% sensitivity and 73.6% specificity for 30 day death or amputation. Kaplan-Meier analysis showed that patients with pre-operative NLR ≥ 5.4 had significantly lower 30 day, six month and one year amputation free survival when compared with those with NLR < 5.4 (64.8 ± 4.0%, 44.1 ± 4.1%, and 37.5 ± 4.1% vs. 98.5 ± 0.9%, 91.9 ± 2.0%, and 85.9 ± 2.5%, log rank p < .001). CONCLUSION: In this study, higher pre-operative NLR was associated with 30 day death or amputation following intervention for Rutherford grade IIa or IIb ALI. NLR potentially stands as a simple, widely available and inexpensive biomarker that can refine decision making and possibly contribute to ALI morbidity and mortality reduction.

Usefulness of Platelet-to-Lymphocyte Ratio as a Marker of Sarcopenia for Critical Limb Threatening Ischemia.

BACKGROUND: Sarcopenia is a factor of poor prognosis for patients with critical limb threatening ischemia (CLTI), but its diagnosis requires imaging measurements and is time consuming. We investigated whether preoperative platelet-to-lymphocyte ratio (PLR) could be an easy and rapid marker of sarcopenia. METHODS: Patients treated for CLTI between January 2019 and July 2019 were included in this single-center retrospective study. Sarcopenia was defined by a psoas muscle index (PMI) <5.5 cm2/m2 in men, and <4.0 cm2/m2 in women. PLR was calculated for all patients based on their systematic preoperative blood analysis. The diagnostic power of PLR was analyzed through a receiver operating characteristic (ROC) curve. Early outcomes of sarcopenic patients in terms of 30-day mortality and 30-day morbidity were retrieved. RESULTS: Sixty-four patients were included in the study: 48 nonsarcopenic patients (mean PMI 7.34 cm2/m2; interquartile range [IQR] 6.58-8.01) and 16 sarcopenic patients (mean PMI 4.30 cm2/m2; IQR 3.45-5.17). No difference was found between both groups regarding patient demographics, clinical characteristics, cardiovascular risk factors, comorbidities, or revascularization modalities. PLR was significantly higher in the sarcopenic group (mean 332.1; IQR 158.2-320.7) compared with the nonsarcopenic group (mean 204.6; IQR 133.8-265.6) (P = 0.02). A PLR value ≥292.5 was shown to be a diagnostic marker for sarcopenia based on the ROC curve (sensitivity 31.3%, specificity 91.7%). Thirty-day mortality was 12.5% in the sarcopenic group and 2.1% in the nonsarcopenic group (P = 0.15); 30-day morbidity was 56.3% in the sarcopenic group and 10.4% in the nonsarcopenic group (P < 0.001). CONCLUSIONS: PLR might help identifying a subgroup of CTLI patients associated with poor prognosis but does not seem appropriate to be used as a marker of sarcopenia given its low sensitivity.

Adoptive transfer of placental ischemia-stimulated natural killer cells causes a preeclampsia-like phenotype in pregnant rats.

PROBLEM: The Reduced Uterine Perfusion Pressure (RUPP) rat model of placental ischemia recapitulates many characteristics of preeclampsia including maternal hypertension, intrauterine growth restriction (IUGR), and increased cytolytic natural killer cells (cNKs). While we have previously shown a 5-fold higher cytotoxicity of RUPP NKs versus normal pregnant NKs, their role in RUPP pathophysiology remains unclear. In this study, we tested the hypotheses that (1) adoptive transfer of RUPP-stimulated NKs will induce maternal hypertension and IUGR in normal pregnant control (Sham) rats and (2) adoptive transfer of Sham NKs will attenuate maternal hypertension and IUGR in RUPP rats. METHOD OF STUDY: On gestation day (GD)14, vehicle or 5 × 106 RUPP NKs were infused i.v. into a subset of Sham rats (Sham+RUPP NK), and vehicle or 5 × 106 Sham NKs were infused i.v. into a subset of RUPP rats (RUPP+Sham NK; n = 12/group). On GD18, Uterine Artery Resistance Index (UARI) was measured. On GD19, mean arterial pressure (MAP) was measured, animals were sacrificed, and blood and tissues were collected for analysis. RESULTS: Adoptive transfer of RUPP NKs into Sham rats resulted in elevated NK activation, UARI, placental oxidative stress, and preproendothelin expression as well as reduced circulating nitrate/nitrite. This led to maternal hypertension and IUGR. RUPP recipients of Sham NKs demonstrated normalized NK activation, sFlt-1, circulating and placental VEGF, and UARI, which led to improved maternal blood pressure and normal fetal growth. CONCLUSION: These data suggest a direct role for cNKs in causing preeclampsia pathophysiology and a role for normal NKs to improve maternal outcomes and IUGR during late gestation.

Double VEGF/HGF Gene Therapy in Critical Limb Ischemia Complicated by Diabetes Mellitus.

Critical leg ischemia (CLI) complicated by diabetes mellitus (DM), which is a very common and dangerous disease, represents the ultimate stage of peripheral arterial disease. Patients are treated with antiplatelet drugs, statins and limb revascularization, but a significant number of patients are not candidate for revascularization. Literature shows that in such cases, gene therapy could be a perfect therapeutic option. The aim of our study was to evaluate efficacy of double vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) gene therapy in patients with CLI complicated by DM. We observed that 90 days after administration, serum level of VEGF and ankle-brachial index increased significantly (p < 0.001) and rest pain decreased significantly compared with the control group (p < 0.002). Moreover considerable improvement in vascularization was observed in computed tomography angiography (P = 0.04). Based on the results of this study, we suggest that the therapy with pIRES/VEGF165/HGF bicistronic plasmid administration is a safe and effective method of treatment of patients with both CLI and DM. Graphical abstract.

Surveillance to detect colonic ischemia with extraluminal pH measurement after open surgery for abdominal aortic aneurysm.

OBJECTIVE: Colonic ischemia (CI) is a life-threatening complication after aortic surgery. Postoperative surveillance of colonic perfusion might be warranted. The aim of the present study was to evaluate the safety and feasibility of postoperative extraluminal pH measurement (pHe) using colonic tonometry after open abdominal aortic aneurysm (AAA) repair. METHODS: Before closing the abdomen after open AAA repair, a tonometric catheter was placed transabdominally in contact with the sigmoid colon serosa, similar to a drainage catheter. Extraluminal partial pressure of carbon dioxide was measured postoperatively and combined with arterial blood gas analysis to calculate the pHe. The measurements were repeated every 4 hours with simultaneous intra-abdominal pressure measurements. The threshold for colonic malperfusion was set at pHe <7.2. RESULTS: A total of 27 patients were monitored, 12 had undergone surgery for ruptured AAAs and 15 for intact AAAs. Of the 27 patients, 4 developed clinically significant CI requiring surgery. All four cases were preceded by a prolonged (>5 hours) pHe <7.2 indicating malperfusion. A fifth patient, who, during monitoring, had had the lowest pHe of 7.21, developed mild CI with the onset after completion of monitoring, which was successfully managed conservatively. Seven patients who had had brief durations (<5 hours) of pHe <7.2 did not develop clinical signs of CI or any related adverse events. CONCLUSIONS: Measurements of pHe using colonic tonometry indicated malperfusion in all four patients who had developed clinically significant CI. A shorter duration of low pHe was well tolerated without any signs of CI. Measurement of pHe was safe and reliable for the surveillance of colonic perfusion after open aortic surgery, indicating a promising technique. However, larger studies are needed.

Novel oxygen saturation imaging endoscopy to assess anastomotic integrity in a porcine ischemia model.

BACKGROUND: Establishing anastomotic integrity is crucial for avoiding anastomotic complications in colorectal surgery. This study aimed to evaluate the safety and feasibility of assessing anastomotic integrity using novel oxygen saturation imaging endoscopy in a porcine ischemia model. METHODS: In three pigs, a new endoscope system was used to check the mechanical completeness of the anastomosis and capture the tissue oxygen saturation (StO2) images. This technology can derive the StO2 images from the differences in the absorption coefficient in the visible light region between oxy- and deoxy-hemoglobin. Bowel perfusion at the proximal rectum was assessed before and after the anastomosis, and 1 min and 30 min after the ligation of the cranial rectal artery (CRA). RESULTS: The completeness of the anastomoses was confirmed by the absence of air leakage. Intraluminal oxygen saturation imaging was successfully performed in all animals. There was no significant difference in the StO2 level before and after the anastomosis (52.6 ± 2.0 vs. 52.0 ± 2.6; p = 0.76, respectively). The StO2 level of the intestine on the oral side of the anastomosis one minute after the CRA ligation was significantly lower than immediately after the anastomosis (15.9 ± 6.0 vs. 52.0 ± 2.6; p = 0.006, respectively). There was no significant difference in the StO2 level between 1 min after and 30 min after the CRA ligation (15.9 ± 6.0 vs. 12.1 ± 5.3; p = 0.41, respectively). CONCLUSION: Novel oxygen saturation imaging endoscopy was safe and feasible to assess the anastomotic integrity in the experimental model.

Trimethylamine N-oxide impairs perfusion recovery after hindlimb ischemia.

BACKGROUND: The circulating level of trimethylamine N-oxide (TMAO) has been reported to be associated with the prognosis of of peripheral arterial disease (PAD) patients. However, the effects of TMAO on neovascularization and perfusion recovery after PAD are not known. METHODS: Unilateral hindlimb ischemia was generated in mice as experimental PAD model, TMAO or 3,3-dimethyl-1-butanol (DMB) were added to the drinking water for these mice. In cultured endothelial cells, TMAO was added to culture medium to assess the effects on cell viability and tube formation under simulated ischemic conditions. RESULTS: In experimental PAD, TMAO treatment increased malondialdehyde (MDA), interleukin (IL)-1ß and IL-6 in the ischemic muscle, impaired perfusion recovery, and decreased capillary density. On the other hand, mice fed with DMB drinking water showed lower TMAO level, interleukin (IL)-1ß and IL-6, and higher vascular endothelial growth factor in the ischemic muscle, and better perfusion recovery after experimental PAD. In cultured endothelial cell, TMAO decreased intracellular nitric oxide, cell viability and tube formation, and increased intracellular reactive oxygen species levels. CONCLUSIONS: TMAO increases oxidative stress and inflammation, and impairs perfusion recovery and angiogenesis in experimental PAD.

A Case of Covid-19 Patient with Acute Limb Ischemia and Heparin Resistance.

Heparin resistance is an uncommon phenomenon defined as the need for high-dose unfractionated heparin (UFH) of more than 35,000 IU/day to achieve the target activated partial-thromboplastin time ratio or the failure to achieve the desired activated clotting time after a full UFH dose. This rare phenomenon is being more commonly observed in Covid-19 patients in a hypercoagulable state. We describe a Covid-19 patient confirmed by reverse-transcriptase polymerase chain reaction assay, with acute limb ischemia, who developed heparin resistance. The patient was managed by the departments of vascular surgery, anesthesia and intensive care, and the Coagulation Service and Thrombosis Research from San Raffaele Scientific Institute, Milan, Italy.

MicroRNA-21/PDCD4 Proapoptotic Signaling From Circulating CD34+ Cells to Vascular Endothelial Cells: A Potential Contributor to Adverse Cardiovascular Outcomes in Patients With Critical Limb Ischemia.

OBJECTIVE: In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34+ cells predicted cardiovascular mortality at 18 months after revascularization. This study aimed to provide long-term validation and mechanistic understanding of the biomarker. RESEARCH DESIGN AND METHODS: The association between CD34+ cell migration and cardiovascular mortality was reassessed at 6 years after revascularization. In a new series of T2D-CLI and control subjects, immuno-sorted bone marrow CD34+ cells were profiled for miRNA expression and assessed for apoptosis and angiogenesis activity. The differentially regulated miRNA-21 and its proapoptotic target, PDCD4, were titrated to verify their contribution in transferring damaging signals from CD34+ cells to endothelial cells. RESULTS: Multivariable regression analysis confirmed that CD34+ cell migration forecasts long-term cardiovascular mortality. CD34+ cells from T2D-CLI patients were more apoptotic and less proangiogenic than those from control subjects and featured miRNA-21 downregulation, modulation of several long noncoding RNAs acting as miRNA-21 sponges, and upregulation of the miRNA-21 proapoptotic target PDCD4. Silencing miR-21 in control CD34+ cells phenocopied the T2D-CLI cell behavior. In coculture, T2D-CLI CD34+ cells imprinted naive endothelial cells, increasing apoptosis, reducing network formation, and modulating the TUG1 sponge/miRNA-21/PDCD4 axis. Silencing PDCD4 or scavenging reactive oxygen species protected endothelial cells from the negative influence of T2D-CLI CD34+ cells. CONCLUSIONS: Migration of CD34+ cells predicts long-term cardiovascular mortality in T2D-CLI patients. An altered paracrine signaling conveys antiangiogenic and proapoptotic features from CD34+ cells to the endothelium. This damaging interaction may increase the risk for life-threatening complications.

Perspectives on Using Platelet-Rich Plasma and Platelet-Rich Fibrin for Managing Patients with Critical Lower Limb Ischemia After Partial Foot Amputation.

The problem of lower limb preservation with symptoms of critical ischemia, resulting in necrosis of the distal foot portion, remains open. These cases require solving few tactical questions, such as the primary revascularization method, limb-preserving amputation, stimulation of regeneration, and finally, determining the criteria for auto-dermal transplantation. We analyzed 29 patient cases with critical lower limb ischemia of fourth grade, according to the Fontaine classification (or the sixth category according to Rutherford's classification), who underwent partial foot amputation due to dry gangrene and were threated using PRGF®-ENDORET® platelet-rich plasma and platelet-rich fibrin technology. The control group was comprised of 21 patients who received traditional postoperative wound treatment. All patients went through a combination of transluminal revascularization and platelet-rich plasma to create a "therapeutic" neoangiogenic effect. Indications for these procedures were severe distal arterial occlusion and stenosis. Using transluminal procedures with platelet-rich plasma therapy improves the blood perfusion to the distal portions of the limb in patients with critical ischemia in a short time, which is an informative diagnostic criterion for wound healing after amputation. Plasmatic membranes create an optimal environment for tissue regeneration, thus reducing the wound closure time using an auto-dermal transplant.

Therapeutic Window of Clopidogrel and Ticagrelor in Patients With Critical Limb-Threatening Ischemia.

BACKGROUND: Critical limb-threatening ischemia (CLTI) is associated with an increased risk of major adverse limb events and mortality. High on-treatment platelet reactivity (HPR) is associated with an increased risk of ischemic events, while low on-treatment platelet reactivity (LPR) is associated with an increased risk of bleeding. This study investigates the frequency with which patients with CLTI on clopidogrel or ticagrelor achieve a "therapeutic window" (TW) of platelet inhibition. METHODS: Data from the "Switch To Ticagrelor in Critical Limb Ischemia Anti-Platelet Study" were assessed retrospectively to determine the incidence of TW of on-treatment platelet reactivity in 50 consecutive patients with CLTI (mean age: 65.2 ± 10.5 years, 54% male). The data included 4 measurements of patients' platelet reactivity using the VerifyNow P2Y12 Assay: baseline and steady state platelet reactivity on clopidogrel 75 mg daily and on ticagrelor 90 mg twice daily. RESULTS: At baseline, 46% of patients on clopidogrel were within TW of on-treatment platelet reactivity compared to 10% of patients on ticagrelor (P < .0001). At steady state, 42% of patients on clopidogrel were within the TW compared to 10% of patients on ticagrelor (P < .0001). Patients on ticagrelor exhibited higher rates of LPR compared to those on clopidogrel at baseline as well as at steady state (baseline 88% vs 18%, steady state 88% vs 28%; P < .0001). CONCLUSION: Although ticagrelor has been proposed as an alternative for patients with HPR on clopidogrel, the current study observes an excess of platelet inhibition with ticagrelor in most patients with CLTI at a dose of 90 mg twice daily.

Relation between serum cotinine levels and trophic lesions in patients with critical limb ischemia: a pilot study.

Aim: To evaluate if smoking, quantified by the serum cotinine levels, is related to the evolution of patients with critical limb ischemia (CLI).Method: A pilot study was conducted on CLI patients who addressed at the Second Surgery Clinic of the Emergency County Hospital, Cluj-Napoca, Romania between November 2015 and December 2016. The sample of patients was split into two groups using the threshold of 15 ng/mL for the serum level of cotinine (low cotinine level - LCL vs. high cotinine level - HCL). Furthermore, the ROC analysis was conducted to identify the threshold of cotinine level able to discriminate between CLI patients with and without trophic lesions.Results: The mean age of patients was 60.7 ± 10.5 years with a significantly higher percentage of male patients (84%). A significant association was identified between urban origin and serum cotinine level, which is related to the increased number of cigarettes smoked per day among urban participants. Excepting necrectomy and toe disarticulation, no differences were found between LCL and HCL group regarding symptoms, signs or comorbidities. In smokers with CLI (38/43), a serum cotinine cut-off of 9.765 ng/mL was observed on eight out of 10 CLI patients with necrectomy and five out of 28 patients without necrectomy.Conclusion: Our study showed higher serum cotinine levels associated with a higher number of smoked cigarettes and necrectomy in patients with CLI. The serum cotinine could be a fair screening test for necrectomy in smokers CLI patients.

The Clinical Outcomes in Patients with Critical Limb Ischemia One Year after Spinal Cord Stimulation.

BACKGROUND: The aim of this study was to evaluate the long-term outcomes of spinal cord stimulation in patients with critical limb ischemia and to test the hypothesis that the dynamics of clinical changes one year after therapy depend both on the clinical determinants associated with the underlying disease and on factors related to systemic atherosclerosis. METHODS: This prospective cohort study included 56 patients with critical limb ischemia. All patients before and after spinal cord stimulation were examined in terms of the dynamics of their clinical changes using the Rutherford scale and transcutaneous oxygen tension (TcPO2, mm Hg) in the affected foot. The active orthostatic test was used to assess the functional state of peripheral perfusion. RESULTS: One year after spinal cord stimulation, 74% of patients showed positive clinical outcomes. No changes were observed in 9.3% of patients, whereas adverse clinical outcomes were revealed in 16.7% of cases. The TcPO2 values were significantly reduced before spinal cord stimulation: 10.5 (6.4-16.0) mm Hg. The functional status of the peripheral microvasculature was also disturbed. One year after therapy, TcPO2 significantly increased and the adaptive mechanisms of the microvasculature were improved in more than 70% of patients. Logistic regression analysis showed that the initially low TcPO2 values (<10 mm Hg) with a lack of gain in TcPO2 during the orthostatic test are associated with the negative clinical outcomes after spinal cord stimulation. The gain in TcPO2 during the orthostatic test to >10 mm Hg is associated with the positive clinical outcomes after spinal cord stimulation. The age-adjusted Charlson Comorbidity Index >5 and duration of critical ischemic symptoms also had a negative effect on the clinical outcomes after spinal cord stimulation. CONCLUSIONS: The positive clinical outcomes were revealed in most patients with critical limb ischemia one year after spinal cord stimulation. The low values of peripheral tissue metabolism with the disturbed functional status of the microvasculature are associated with the negative clinical outcome. The patients with baseline TcPO2 <10 mm Hg can recover if they still have a sufficient microcirculatory reserve capacity. Duration of critical ischemic symptoms and high comorbidity burden with allowance for age are negative factors affecting the clinical outcome.