The role of oxidative stress in neurodegenerative diseases and potential antioxidant therapies.

Objectives: The central nervous system (CNS) is essential for homeostasis and controls the physiological functions of the body. However, the biochemical characteristics of the CNS make it especially vulnerable to oxidative damage (OS). This phenomenon compromises correct CNS functioning, leading to neurodegeneration and neuronal death. Contents: OS plays a crucial role in the physiopathology of neurodegenerative diseases. It is involved in multiple mechanisms of nucleic acid, protein, and lipid oxidation, thereby contributing to progressive brain damage. These mechanisms include mitochondrial dysfunction; excessive production of reactive oxygen and nitrogen species; deficiency of antioxidant defenses; protein oligomerization; cytokine production and inflammatory response; blood-brain barrier abnormalities; and proteasome dysfunction. All these dysfunctions are involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, or amyotrophic lateral sclerosis. Summary and outlook: A curative treatment is currently not available. Research is focused on the search for therapies that reduce oxidative damage and delay disease progression. In the recent years, researchers have focused their attention on the effects of antioxidant therapies.

Circulating levels of calprotectin, a signature of neutrophil activation in prediction of severe respiratory failure in COVID-19 patients: a multicenter, prospective study (CalCov study).

OBJECTIVE: Severe COVID-19 is characterized by a dysregulated immune response in which neutrophils play a critical role. Calprotectin reflects neutrophil activation and is involved in the self-amplifying thrombo-inflammatory storm in severe COVID-19. We aimed to evaluate the role of calprotectin in early prediction of severity in COVID-19 patients. METHODS: This was a multicenter prospective observational study enrolling consecutive adult COVID-19 patients. On arrival to emergency department, blood samples were collected for laboratory tests, including serum calprotectin. The primary outcome was severe respiratory failure requiring invasive mechanical ventilation and the secondary outcome was need for Intensive Care Unit (ICU) admission. RESULTS: Study population included 395 patients, 57 (14.4%) required invasive mechanical ventilation and 100 (25.3%) were admitted to ICU. Median serum calprotectin levels were significantly higher in intubated (3.73 mg/L vs. 2.63 mg/L; p < 0.001) and ICU patients (3.48 mg/L vs. 2.60 mg/L; p = 0.001). Calprotectin showed a significant accuracy to predict the need for invasive mechanical ventilation (ROC AUC 0.723) and ICU admission (ROC AUC 0.650). In multivariate analysis, serum calprotectin was an independent predictor of invasive mechanical ventilation (OR 1.161) and ICU admission (OR 1.068). CONCLUSION: Serum calprotectin can be used as an early predictor of severity in COVID-19 patients.

Discordant SOX-1 antibodies results in paraneoplastic Lambert-Eaton syndrome diagnosis by the clinical laboratory.

BACKGROUND: Anti-Sry-like high mobility group box 1 (anti SOX-1) proteins are rare onconeural antibodies associated with paraneoplastic Lambert-Eaton myasthenic syndrome (LEMS). Few patients with anti-SOX-1 antibodies and negative anti-glial nuclear antibody reactivity have been described to date. CASE SUBJECT AND METHODS: Our case involves a 72-year-old female patient with progressive girdle weakness, sensation of heaviness in the lower limbs, predominantly distal and associated with circulatory problems together with instability when walking, with a high suspicion of an autoimmune myopathic disorder. Immunoblot test for autoimmune myopathies antibodies detection were all negative. Onconeuronal antibodies were determined in serum by indirect immunofluorescence being negative as well. Given the high suspicion, we also checked for the presence of other antineuronal antibodies whose patterns are not visible by IIF. RESULTS: Onconeuronal antibodies by immunoblot for the following antibodies: Hu, Ri, Yo, Zic4, Tr, PCA-2, MA-TA, CV2, GAD65, Zic4, Titin, SOX1, Recoverin and Amp, revealed an unexpected clear band in SOX-1, which are highly suggestive of paraneoplastic LEMS. DISCUSSION: We hypothesize that discordant onconeuronal antibodies results were due to the fact that positivity in IIF is associated with other SOX-B group proteins (normally related to cases of non-paraneoplastic neuropathy), while negativity in IIF and subsequent confirmed presence of specific SOX1 antibody by immunoblot could indicate an underlying tumor.

Decision support system through automatic algorithms and electronic request in diagnosis of anaemia for primary care patients.

INTRODUCTION: An appropriate management of anaemia laboratory tests is crucial for a correct diagnosis and treatment. A non-sequential "shotgun" approach (where every anaemia related test is ordered) causes workload and cost increases and could be potentially harmful. We have implemented a Decision Support System through our laboratory information system (LIMS) based on reflexive algorithms and automatic generation of interpretative reports specifically in diagnosis of anaemia for primary care patients. MATERIALS AND METHODS: When a request contained an "Anaemia Suspicion Study" profile, more than twenty automatic reflexive rules were activated in our LIMS based upon laboratory results. These rules normally involved the addition of reflexive tests. A final report was automatically generated for each interpretation which was always reviewed for their validity by two staff pathologists. We measured the impact of this system in the ordering of most common anaemia related tests and if a proper treatment was established based on the interpretive report. RESULTS: From all the studies performed, only 12% were positive being "iron deficiency" and "anaemia of chronic disease" the most frequent causes, 62% and 17%, respectively. Proper treatment was established in 88% of these anaemic patients. Total iron, transferrin, ferritin, folate and vitamin B12 demand decreased substantially after implementation representing a cost reduction of 40% only for these five tests. CONCLUSIONS: Our system has easily improved patient outcomes, advising on individual clinical cases. We have also noticeably reduced the number of over-requested tests and laboratory costs.