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Background: Hyperhomocysteinemia (HHcy) is considered as an independent risk factor for several diseases, such as cardiovascular, neurological and autoimmune conditions. Atherothrombotic events, as a result of endothelial dysfunction and increased inflammation, are the main mechanisms involved in vascular damage. This review article reports clinical evidence on the relationship between the concentration of plasmatic homocysteine (Hcy) and acute brain injury (ABI) in neurocritical care patients., Materials and Methods: a systematic search of articles in the PubMed and EMBASE databases was conducted, of which only complete studies, published in English in peer-reviewed journals, were included., Results: A total of 33 articles, which can be divided into the following 3 subchapters, are present: homocysteine and acute ischemic stroke (AIS); homocysteine and traumatic brain injury (TBI); homocysteine and intracranial hemorrhage (ICH)/subarachnoid hemorrhage (SAH). This confirms that HHcy is an independent risk factor for ABI and a marker of poor prognosis in the case of stroke, ICH, SAH and TBI., Conclusions: Several studies elucidate that Hcy levels influence the patient's prognosis in ABI and, in some cases, the risk of recurrence. Hcy appears as biochemical marker that can be used by neuro-intensivists as an indicator for risk stratification. Moreover, a nutraceutical approach, including folic acid, the vitamins B6 and B12, reduces the risk of thrombosis, cardiovascular and neurological dysfunction in patients with severe HHcy that were admitted for neurocritical care.

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A "training sample" (March-June 2020) and a "testing sample" (September 2020-January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO 2 /FiO 2 ratio, and sample (training/testing). "Training" and "testing" samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH 2 O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH 2 O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.