Narrative Review of Biological Markers in Chronic Limb-Threatening Ischemia.

BACKGROUND: Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI. METHODS: A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched-Web of Science, Medline, and EMBASE-for the studies assessing CLTI and the biological markers related to it. RESULTS: We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients. CONCLUSIONS: All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.

A Signal Processing Method for Assessing Ankle Torque with a Custom-Made Electronic Dynamometer in Participants Affected by Diabetic Peripheral Neuropathy.

Portable, custom-made electronic dynamometry for the foot and ankle is a promising assessment method that enables foot and ankle muscle function to be established in healthy participants and those affected by chronic conditions. Diabetic peripheral neuropathy (DPN) can alter foot and ankle muscle function. This study assessed ankle toque in participants with diabetic peripheral neuropathy and healthy participants, with the aim of developing an algorithm for optimizing the precision of data processing and interpretation of the results and to define a reference frame for ankle torque measurement in both healthy participants and those affected by DPN. This paper discloses the software chain and the signal processing methods used for voltage-torque conversion, filtering, offset detection and the muscle effort type identification, which further allowed for a primary statistical report. The full description of the signal processing methods will make our research reproducible. The applied algorithm for signal processing is proposed as a reference frame for ankle torque assessment when using a custom-made electronic dynamometer. While evaluating multiple measurements, our algorithm permits for a more detailed parametrization of the ankle torque results in healthy participants and those affected by DPN.

Acute Effects of Sedentary Behavior on Ankle Torque Assessed with a Custom-Made Electronic Dynamometer.

Inactivity negatively influences general health, and sedentary behaviour is known to impact the musculoskeletal system. The aim of the study was to assess the impact of time spent in active and sedentary behaviour on foot muscle strength. In this observational study, we compared the acute effects of one day of prolonged sitting and one day of low-to-moderate level of activity on ankle torque in one group of eight healthy participants. Peak ankle torque was measured using a portable custom-made electronic dynamometer. Three consecutive maximal voluntary isometric contractions for bilateral plantar flexor and dorsiflexor muscles were captured at different moments in time. The average peak torque significant statistically decreased at 6 h (p = 0.019) in both static and active behaviours, with a higher average peak torque in the active behaviour (p < 0.001). Age, gender, body mass index and average steps did not have any significant influence on the average value of maximal voluntary isometric contraction. The more time participants maintained either static or active behaviour, the less force was observed during ankle torque testation. The static behaviour represented by the sitting position was associated with a higher reduction in the average peak ankle torque during a maximal voluntary isometric contraction when compared to the active behaviour.

True Brachial Artery Aneurysm in Patients with Previous Arterio-Venous Fistula Ligation and Immunosuppressant Therapy for Renal Transplantation: Case Report and Literature Review.

BACKGROUND/OBJECTIVE: Brachial artery aneurysm (BAA) is a serious complication in patients with previous arterio-venous fistula (AVF), renal transplantation (RT), and immunosuppressive regimens. Until now, there has been no standard of care for these patients, especially for patients undergoing chronic dialysis and immunosuppressive treatment. The aim of this study was to investigate data from the literature regarding these patients and to suggest recommendations for the best approach to their treatment. METHODS: A review of the literature was performed by searching the PubMed database in the English language. The review was accompanied by two case reports. A total of 24 articles with different variables-demographics, renal transplantation, aneurysm size, and type of surgery-were subjected to the review. In addition, two cases are reported. CONCLUSION: This review suggests that the best treatment for these patients is open surgery, with aneurysmectomy and graft interposition. RESULTS: All patients had RT. The age of patients ranged from 26-77 yo, with a male predominance. The majority had an AVF ligated after RT. The main clinical symptoms were pain, swelling, and pulsatile mass (66%). All patients, except one, were treated through open surgery. The first option for treatment was reversed saphenous vein graft interposition (36%), followed by ePTFE graft (16%).

An In Vivo Observational Histological Study of Peripheral Arterial Damage in Patients with Acute Limb Ischemia in SARS-CoV-2 Infection.

Thromboembolic events, such as acute limb ischemia, were reported worldwide in patients with COVID-19, suggesting that SARS-CoV-2 infection acts like a redoubtable prothrombotic factor in these patients. The aim of the study was to summarize the histopathological changes found in the arterial wall, intraarterial thrombus, and adjacent skeletal muscles. Considering the lack of evidence from in vivo studies, we performed observational histological research of peripheral arterial damage in patients with acute limb ischemia and SARS-CoV-2 infection. We investigated 22 patients with acute limb ischemia and SARS and harvested histopathological samples from those who agreed to this procedure. We performed histologic tissue harvesting during the revascularization procedure from the thrombosed area of the common femoral artery. Morphologic analysis was made on the hematoxylin-eosin (HE) stain. Special stains were also used-Elastica van Gieson (EvG) and Alcian Blue-Periodic Acid-Schiff (AB-PAS) and primary antibodies-CD45 and CD61. Our patients had significant risk factors for thrombus formation, since all of them had arterial hypertension, 81% had dyslipidemia, 73% were obese, 63% suffered from diabetes mellitus, and 45% were active smokers. The histological findings using immunohistochemistry (CD45 and CD68 reactions) or special and usual stains underlined the mechanism for ischemia production in SARS-CoV-2 patients. The main histological findings in our study were endothelial destruction and inflammation that were found in all analyzed structures.

An Observational Study on Patients with Acute Limb Ischemia and SARS-CoV-2 Infection: Early and Late Results in Limb Salvage Rate.

An observational study on 22 patients presenting with acute limb ischemia and SARS-CoV-2 infection, and without any other embolic risk factors, was performed. All patients were classified according to Rutherford classification for acute limb ischemia. The primary goal of this study was to assess the risk of amputation in these patients after revascularization procedures. The secondary goal was to find the correlation between acute limb ischemia (ALI) severity, patient comorbidities, risk of death, and the association of SARS-CoV-2 infection. The patients were treated by open surgery (18 patients-81.81%) or by the means of endovascular techniques (four patients-18.18%). The amputation-free survival rate was 81.81% in hospital and 86.36% at 1-month follow-up. In this study, the presence of SARS-CoV-2 infection did not influence the amputation-free survival rate: it was only the risk factor for the arterial thrombosis and the trigger for the acute ischemic event. The application of the standard treatment-open surgery or endovascular revascularization-in patients with acute limb ischemia and SARS-CoV-2 infection represents the key to success for lower limb salvage.

Work-Related Musculoskeletal Complaints in Surgeons.

The aim of the present study was to examine the prevalence of work-related musculoskeletal complaints and potential risk factors among Romanian surgeons. Ninety-five surgeons of different specialties (62.11% males) completed a questionnaire about work-related musculoskeletal complaints (WMSCs). Ninety-one surgeons (95.78%) experienced WMSCs at least in one body part in the last year. Most surgeons reported pain in four body parts (33.68%). The most common WMSCs were reported on the lower back (74.73%), followed by complaints in the neck region (55.79%), shoulder and upper back (46.32%), knee (31.58%), wrist-hand (16.84%), elbow (14.74%), hip (11.58%) and ankle-foot (4.21%). Surgeons rated their pain more severe on upper back, lower back and knees. A higher percentage of male surgeons reported upper back pain (χ2(1) = 5.818, p = 0.015). Significant age differences were found between the reported pain sites (F8,278 = 2.666, p = 0.008); the surgeons reporting wrist-hand pain were younger than those reporting neck, shoulders, elbows, dorsal and lumbar pain. Surgeons with significantly less experience in years reported significantly more WMSCs in wrist-hand, hip and ankle-foot regions compared with those more experienced (p < 0.05). Surgeons are at high risk of developing work-related musculoskeletal complaints, which affects both their professional and personal life. Further studies are needed to identify all risk factors and ergonomic strategies to reduce the prevalence and the negative impact of WMSCs.

Role of Reconstructive Microsurgery in Tubal Infertility in Young Women.

AIM: Here, we retrospectively analyzed the success rate of reconstructive microsurgery for tubal infertility (RMTI) as a "first-line" approach to achieving tubal reversal and pregnancy after tubal infertility. PATIENTS AND METHODS: During 9 consecutive years (2005-2014), 96 patients diagnosed with obstructive tubal infertility underwent RMTI (tubal reversal, salpingostomy, and/or tubal implantation) in our centre. The outcomes are presented in terms of tubal reversal rate and pregnancy and correlated with age, level of tubal obstruction, and duration of tubal infertility. RESULTS: The overall tubal reversal rate was 87.56% (84 patients). The 48-month cumulative pregnancy rate was 78.04% (64 patients), of which seven ectopic pregnancies occurred (8.53%). The reversibility rate for women under 35 yo was 90.47%, with a birth rate of 73.01%. The reconstruction at the infundibular segments favored higher ectopic pregnancy rates (four ectopic pregnancies for anastomosis at infundibular level-57.14%, two for ampullary level-28.57%, and one for replantation technique-14.28%), with a significant value for p < 0.05. CONCLUSIONS: In the context of IVF "industrialization", reconstructive microsurgery for tubal infertility has become increasingly less favored. However, under available expertise and proper indication, RMTI can be successfully used to restore a woman's ability to conceive naturally with a high postoperative pregnancy rate overall, especially in women under 35 yo.

Chronic Hindlimb Ischemia Assessment; Quantitative Evaluation Using Laser Doppler in a Rodent Model of Surgically Induced Peripheral Arterial Occlusion.

Therapeutic neoangiogenesis (TNA) holds promise as a treatment for peripheral arterial disease. Nevertheless, proper tools for in vivo pre-clinical investigation of different TNA approaches and their effects are still lacking. Here we describe a chronic ischemic hindlimb model in rats using laser Doppler quantitative evaluation of tissue perfusion. Male Wistar rats (n = 20), aged between 6-8 months, with an average weight of 287 ± 26.74 g, were used. Animals were divided into two experimental groups: group A (n = 17; hindlimb chronic ischemia model) and group B (n = 3; control). Hindlimb ischemia was induced by concomitant ligation of the right femoral and popliteal artery. Evaluation of tissue perfusion was quantified in perfusion units (PU) on a scale from 0 to 500 (500 PU = maximal detectable perfusion) by laser Doppler analysis at day 0, day 15 and day 30 after induction of ischemia. Induction of chronic ischemia in the rat hindlimb by concomitant ligation of the femoral and popliteal artery can be readily obtained but requires basic microsurgical skills. Laser Doppler analysis has shown unaltered ischemia levels throughout the study (129,17 PU ± 3.13 day 0 vs. 130,33 PU day 30 ± 3,27, p = not significant (n.s.)). We demonstrate a simple and reproducible model of chronic hindlimb ischemia in rats, with stable tissue perfusion levels that are accurately quantified using laser Doppler technology. Hence, this model can represent a valid tool for further studies involving therapeutic neoangiogenesis.

Induction of therapeutic neoangiogenesis using in vitro-generated endothelial colony-forming cells: an autologous transplantation model in rat.

BACKGROUND: Accumulating evidence shows the potential of bone marrow-derived endothelial colony-forming cells (bmECFCs) as promising tools for vascular repair. However, knowledge about their in vitro expansion, characterization, and functional behavior is still controversial. We demonstrate the in vitro generation of rat bmECFCs and analyze their ability to promote tissue reperfusion in a chronic hind-limb ischemia model. METHODS: Either in vitro-generated and characterized autologous bmECFCs or placebo was injected into ischemic hind limbs of Sprague-Dawley rats. Tissue perfusion was quantified by laser Doppler, in perfusion units (PU), at days 0, 15, and 30. RESULTS: Rat bmECFCs acquire a typical phenotype (CD34(+)VEGFR2(+)CD133(+)CXCR4(+)CD45(-)), culture, and functional behavior (Dil-ac-LDL+) in vitro. Injection of autologous bmECFCs improves tissue perfusion in ischemic hind limbs (183.5 ± 3.29 PU(bmECFCs/day 30)versus 131 ± 3.9 PU(controls/day 30), P < 0.001). CONCLUSIONS: We conclude that rat bmECFCs promote ischemic tissue reperfusion and their proangiogenic properties are a potential mechanism for this effect.

Hindpaw withdrawal from a painful thermal stimulus after sciatic nerve compression and decompression in the diabetic rat.

INTRODUCTION: Although the effect of chronic compression and surgical decompression of the diabetic rat sciatic nerve has been evaluated by walking track analysis, the measurement of sensory function by response to thermal nociceptive stimulation has not been investigated. METHODS: Fifteen male Wistar rats with streptozotocin-induced diabetes underwent sciatic nerve compression through a 10-mm silicone band. Five rats had histology done 60 days after confirming chronic nerve compression. Pain threshold was measured using hindlimb withdrawal times (HLWT) from a heat stimulus. After 60 days of compression, the silicone tube was removed. Five nondiabetic, nonbanded rats were used as controls. RESULTS: Control mean HLWT was 9.7 ± 1.5 sec. In the diabetes group (60 days of compression), mean HLWT was 23.6 ± 2.4 sec. (p < 0.001). Thirty days after removal of the silicone, mean HLWT to painful stimuli was 14.9 ± 1.5 sec. (p < 0.001). CONCLUSION: Chronic compression of the diabetic rat sciatic nerve increases (worsens) the threshold to heat (pain) perception. Decompression reverses this effect (improves nociception).

The versatility of propeller flaps for lower limb reconstruction in patients with peripheral arterial obstructive disease: initial experience.

In this study, we evaluate the feasibility of propeller flaps, for soft tissue reconstruction in patients with peripheral arterial obstructive disease (PAOD). Five patients (average age, 72 years old), presenting with necrosis of several foot units, were diagnosed with stage IV PAOD and diabetes mellitus. All underwent revascularization, followed by soft tissue reconstruction using propeller flaps. A total of 6 flaps were performed, with dimensions ranging from 4 x 7 cm to 8 x 31 cm. Perforator origin was the peroneal (5 flaps) or the tibial posterior artery (1 flap). Average operative time was 190 minutes. Overall patency was 83.3%; 1 case was complicated with total flap loss followed by below-knee amputation; 1 case developed partial necrosis necessitating skin grafting. All flaps developed mild postoperative edema, which resolved spontaneously. Propeller flaps prove to be useful tools for soft tissue reconstruction in patients with PAOD because of low operative morbidity, easy technique with fast learning curve, and low complications rate.