Coagulopathy, thromboembolic complications, and the use of heparin in COVID-19 pneumonia.

The SARS-CoV-2 (COVID-19) is causing a pandemic and potentially fatal disease of global public health concern. Viral infections are known to be associated with coagulation impairment; thus, thrombosis, hemorrhage, or both may occur. Understanding the pathophysiologic mechanisms underlying the development of coagulation disorders during viral infection is essential for the development of therapeutic strategies. Coagulopathy in COVID-19 infection is emerging as a precipitant factor for severe respiratory complications and death. An increase in coagulation markers, such as fibrinogen and D-dimer, has been found in severe COVID-19 cases. Heparin, clinically used as an anticoagulant, also has anti-inflammatory properties, including binding of inflammatory cytokines, inhibition of neutrophil chemotaxis, and protection of endothelial cells, and a potential antiviral effect. We hypothesized that low-molecular-weight heparin may attenuate cytokine storm in COVID-19 patients; therefore, low-molecular-weight heparin could be a valid adjunctive therapeutic drug for the treatment of COVID-19 pneumopathy. In this paper, we review potential mechanisms involved in coagulation impairment after viral infection and the possible role of heparin in the treatment of COVID-19 patients.

Gamma Knife Radiosurgery for Short Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing (SUNCT) Syndrome: Targeting the Trigeminal Nerve and the Sphenopalatine Ganglion. Case Report and Literature Review.

BACKGROUND: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a primary headache syndrome with an unclear pathogenesis, and only in very few cases, SUNCT is secondary to known lesions (secondary SUNCT). Several pharmacological as well as interventional and invasive treatments have been used to treat SUNT cases, with no definitive results. We describe a patient with idiopathic SUNCT syndrome, successfully treated with gamma knife radiosurgery and we report a review of the cases of the literature treated with radiosurgery. CASE REPORT: A 63-year-old woman complained of episodes of intense and regular paroxysmal facial pain in the territory of the maxillary branch of the trigeminal nerve accompanied by inflammation of conjunctiva and involuntary lacrimation from 2006. During the following years, she received several treatments: combination of drugs, acupuncture, and endonasal infiltration of the sphenopalatine ganglion. The frequency of the painful attacks increased progressively and it was impossible for her to have a normal active life. Combined gamma knife radiosurgery treatment, targeting the trigeminal nerve (80 Gy maximum dose) and the sphenopalatine ganglion (80 Gy maximum dose) was performed in April 2016 (visual analog score before treatment = 6). Pain gradually reduced in the following months, as well as frequency and severity of the attacks. No sensory deficit developed. The follow-up length of our patient is 37 months: she is nearly pain free (visual analog score = 2) and has resumed a normal life. CONCLUSIONS: Patients with idiopathic SUNCT have few therapeutic options. Our case demonstrates that gamma knife radiosurgery is a feasible and effective noninvasive option to treat patients with medically refractory idiopathic SUNCT.

[Late recovery of renal function in a patient with acute on chronic renal failure treated with peritoneal dialysis]. / Tardivo recupero della funzione renale in un paziente con insufficienza renale acuta su cronica trattato con dialisi peritoneale.

Contrast-induced nephropathy has become a significant source of hospital morbidity and mortality particularly in patients with multi-organs defects. No current treatment can reverse or ameliorate contrast induced nephropathy once it occurs, but prophylaxis is possible. We present the case of a 61-year-old male patient with concomitant chronic kidney disease (CKD stage III K/DOQI) and diabetes complicated by severe multi-vascular disease, who developed acute kidney damage probably due to the simultaneously exposure to intravascular contrast media and cholesterol crystal embolism. In addition, owing to rapid deterioration of renal function, this patient started renal replacement therapy. No renal biopsy was performed due to the poor clinical condition of the patient. After a month of hemodialysis, he switched to a peritoneal dialysis procedure to which specific treatment for vascular lesions, including antibiotics, prostanoids, hyperbaric oxygen therapy, antiaggregants/anticoagulants and physiotherapy, was associated. After 7 months, the dialysis treatment was stopped and he began intensive clinical follow-up. At present, the patient is in conservative medical treatment (the Tenckhoff catheter has been removed), he is in good condition and severe vascular lesions are absent. Our conclusion is that contrast-induced nephropathy in vasculopathic diabetic patients requires a multidisciplinary approach. In particular, good cooperation between nephrologists and angiologists is useful to avoid rapid and chronic deterioration of renal failure and to prevent the onset and development of severe vascular damage.

Effect on walking distance and atherosclerosis progression of a nitric oxide-donating agent in intermittent claudication.

BACKGROUND: Peripheral arterial disease (PAD) is almost invariably associated with a generalized atherosclerotic involvement of the arterial tree and endothelial dysfunction. Previous short-term studies showed improvement of vascular reactivity and walking capacity in PAD patients by measures aimed at restoring nitric oxide (NO) production. NO is also known to prevent the progression of atherosclerosis. We wished to assess whether the prolonged administration of an NO-donating agent (NCX 4016) improves the functional capacity of PAD patients and affects the progression of atherosclerosis as assessed by carotid intima-media thickness (IMT). METHODS: This prospective, double-blind, placebo-controlled study enrolled 442 patients with stable intermittent claudication who were randomized to NCX 4016 (800 mg, twice daily) or its placebo for 6 months. The primary study outcome was the absolute claudication distance on a constant treadmill test (10% incline, 3 km/h). The main secondary end point was the change of the mean far-wall right common carotid artery IMT. RESULTS: The increase of absolute claudication distance at 6 months compared with baseline was 126±140 meters in the placebo-treated group and 117±137 meters in the NCX 4016-treated group, with no significant differences. Carotid IMT increased in the placebo-treated group (+0.01±0.01 mm; P=.55) and decreased in the NCX 4016-treated group (-0.03±0.01 mm; P=.0306). Other secondary end points did not differ between the two treatments. CONCLUSIONS: Long-term NO donation does not improve the claudication distance but does reduce progression of atherosclerosis in patients with PAD. Further studies aimed at assessing whether long-term NO donation may prevent ischemic cardiovascular events are warranted.

Endothelial progenitor cells in patients with severe peripheral arterial disease.

The aims of this study were to investigate the interrelationships between endothelial progenitor cells (EPCs), peripheral arterial disease (PAD), and atherosclerotic risk factors, as only limited data are available regarding the EPCs in patients with PAD. The authors studied the number of EPCs by different methods in a carefully selected group of 45 patients with PAD along with 24 healthy subjects (HS). In patients with PAD, by utilizing the dual-binding method, the number of EPCs was significantly increased compared to HS (M +/- SD, PAD: 73 +/- 33, HS: 52 +/- 20 EPCs/high power field; p < .001). On the contrary, both CD34(+) cell count and CD133(+) cell count were significantly decreased compared to HS. Colony-forming units were significantly increased in PAD compared to HS (median and 25th and 75th percentiles, PAD: 7, 1, 9; HS: 1, 1, 4 CFU/well, respectively; Mann-Whitney, p = .006). In patients with PAD, the number and proliferative activity of circulating EPCs are increased with respect to HS even though EPC count by flourecence-activated cell sorting (FACS) analysis provided different results and this may explain the discrepancy in data collected using different methods. The regulation of the number and biological activity of EPCs in PAD remains unclear.

Effect of glutathione infusion on leg arterial circulation, cutaneous microcirculation, and pain-free walking distance in patients with peripheral obstructive arterial disease: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the effects of glutathione on pain-free walking distance (PFWD) and hemodynamic parameters in patients with peripheral artery disease. PATIENTS AND METHODS: Forty patients with Fontaine stage II peripheral artery disease who were seen between September 2000 and March 2001 at the vascular laboratory and ward of the Division of Vascular Medicine and Rehabilitation at Verona University were studied in a double-blind, placebo-controlled trial. The patients were randomly assigned (20 per group) to treatment with intravenous glutathione twice a day or saline solution twice a day for 5 days. Treatments were administered in a double-blind manner. The 2 groups of patients underwent measurement of PFWD by strain-gauge plethysmography and laser Doppler flowmetry (with postischemic test) of the symptomatic leg at rest and after treadmill test. All measurements and tests were repeated 12 hours after the last infusion. RESULTS: Between the 2 groups, hemodynamic tests showed no differences in baseline values and at rest after treatment. At rest, no differences were observed between basal and posttreatment values; findings in the saline group were similar during tests before and after the infusion period. In the glutathione group, we observed increases in PFWD (196+/-15 vs 143+/-11 m; P<.04), macrocirculatory flow after treadmill test with plethysmography at the end of treatment (9.3+/-2 vs 2.8+/-0.5 mL per 100 mL/min; P<.002), and postischemic hyperemia with laser Doppler flowmetry, registered as perfusion units (PU), at the end of infusions (14.4+/-3.2 vs 6.18+/-1.5 PU; P<.005), with a greater area under the curve after treatment (705+/-103 vs 508+/-45 PU/s; P<.001) and reduced time to flow motion (32+/-4 vs 48+/-11 seconds; P<.05). CONCLUSION: In patients with peripheral artery disease, glutathione prolongs PFWD and shows an improvement of macrocirculatory and microcirculatory parameters.