ULTRASOUND AS FIRST LINE STEP IN ANAEMIA DIAGNOSTICS

This review covers the role of ultrasonography as an essential non-invasive diagnosti

Aceruloplasminemia: A Severe Neurodegenerative Disorder Deserving an Early Diagnosis

Aceruloplasminemia (ACP) is a rare, adult-onset, autosomal recessive disorder, characterized by systemic iron overload due to mutations in the Ceruloplasmin gene (CP), which in turn lead to absence or strong reduction of CP activity. CP is a ferroxidase that plays a key role in iron export from various cells, especially in the brain, where it maintains the appropriate iron homeostasis with neuroprotective effects. Brain iron accumulation makes ACP unique among systemic iron overload syndromes, e.g., various types of genetic hemochromatosis. The main clinical features of fully expressed ACP include diabetes, retinopathy, liver disease, and progressive neurological symptoms reflecting iron deposition in target organs. However, biochemical signs of the disease, namely a mild anemia mimicking iron deficiency anemia because of microcytosis and low transferrin saturation, but with "paradoxical" hyperferritinemia, usually precedes the onset of clinical symptoms of many years and sometimes decades. Prompt diagnosis and therapy are crucial to prevent neurological complications of the disease, as they are usually irreversible once established. In this mini-review we discuss some major issues about this rare disorder, pointing out the early clues to the right diagnosis, instrumental to reduce significant disability burden of affected patients

Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?

Even though COVID-19 is mostly well-known for affecting respiratory pathology, it can also result in several extrapulmonary manifestations, leading to multiorgan damage. A recent reported case of SARS-CoV-2 myocarditis with cardiogenic shock showed a signature of myocardial and kidney ferroptosis, a novel, iron-dependent programmed cell death. The term ferroptosis was coined in the last decade to describe the form of cell death induced by the small molecule erastin. As a specific inducer of ferroptosis, erastin inhibits cystine-glutamate antiporter system Xc-, blocking transportation into the cytoplasm of cystine, a precursor of glutathione (GSH) in exchange with glutamate and the consequent malfunction of GPX4. Ferroptosis is also promoted by intracellular iron overload and by the iron-dependent accumulation of polyunsaturated fatty acids (PUFA)- derived lipid peroxides. Since depletion of GSH, inactivation of GPX4, altered iron metabolism, and upregulation of PUFA peroxidation by reactive oxygen species are peculiar signs of COVID-19, there is the possibility that SARS-CoV-2 may trigger ferroptosis in the cells of multiple organs, thus contributing to multiorgan damage. Here, we review the molecular mechanisms of ferroptosis and its possible relationship with SARS-CoV-2 infection and multiorgan damage. Finally, we analyze the potential interventions that may combat ferroptosis and, therefore, reduce multiorgan damage

On-line separation and determination of trivalent and hexavalent chromium with a new liquid membrane annular contactor coupled to inductively coupled plasma optical emission spectrometry

We describe a new on-line sensitive and selective procedure for the determination of trivalent and hexavalent chromium in liquid samples by a tailor-made contactor (TMC), specifically a liquid membrane annular TMC, coupled with inductively coupled plasma with optical detection. The TMC was designed and developed to integrate the extraction and stripping phases of the analyte in one module to minimize the membrane solvent’s consumption and maximize the speed of transport through the liquid membrane. Moreover, the particular geometry studied, which consists of two coaxial hollow fibers, allows the TMC to be used for both separating and preconcentrating purposes. Both (−)-N-dodecyl-N-methylephedrinium bromide (30 mM) in dichloroethane and HNO3 (0.75 M) were used as the liquid membrane and receiving solution, re-spectively. The proposed method’s performance was evaluated in terms of the hexavalent chro-mium extraction efficiency and the coefficient of variation percentages; these were higher than 85% and less than 5%, respectively. In addition, the proposed procedure was applied to two real sam-ples: a tap water sample and an eluate from solid urban waste. In both cases, the analytical per-formances were good and comparable to those obtained using synthetic standard solutions

an unusual case of acute abdominal pain

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Systemic Inflammatory Response and Outcomes in Community-Acquired Pneumonia Patients Categorized According to the Smoking Habit or Presence of Chronic Obstructive Pulmonary Disease

The systemic inflammatory response (SIR) may help to predict clinical progression, treatment failure, and prognosis in community-acquired pneumonia (CAP). Exposure to tobacco smoke may affect the SIR; the role of smoking in CAP has not been consolidated. We evaluated the SIR and outcomes of hospitalized CAP patients stratified by smoking habits and the presence of COPD. This retrospective analysis was conducted at the Hospital Clinic of Barcelona. Baseline, clinical, microbiological, and laboratory variables were collected at admission, using C-reactive protein (CRP) levels as a marker of SIR. The study outcomes were pleural complications, hospital stay, non-invasive and invasive mechanical ventilation (IMV), and intensive care unit (ICU) admission. We also considered the in-hospital and 30-day mortality. Data were grouped by smoking habit (non-, former-, and current-smokers) and the presence of COPD. Current smokers were younger, had fewer comorbidities, and fewer previous pneumonia episodes. CRP levels were higher in current smokers than in other groups. Current smokers had a higher risk of pleural complications independent of CRP levels, the presence of pleuritic pain, and a higher platelet count. Current smokers more often required IMV and ICU admission. Current smokers have a greater inflammatory response and are at increased risk of pleural complications

New Insights into the Role of Ferroptosis in Cardiovascular Diseases

Cardiovascular diseases (CVDs) are the principal cause of disease burden and death worldwide. Ferroptosis is a new formof regulated cell deathmainly characterized by altered ironmetabolism, increased polyunsaturated fatty acid peroxidation by reactive oxygen species, depletion of glutathione and inactivation of glutathione peroxidase 4. Recently, a series of studies have indicated that ferroptosis is involved in the death of cardiac and vascular cells and has a key impact on the mechanisms leading to CVDs such as ischemic heart disease, ischemia/reperfusion injury, cardiomyopathies, and heart failure. In this article, we reviewed the molecular mechanism of ferroptosis and the current understanding of the pathophysiological role of ferroptosis in ischemic heart disease and in some cardiomyopathies. Moreover, the comprehension of the machinery governing ferroptosis in vascular cells and cardiomyocytes may provide new insights into preventive and therapeutic strategies in CVDs

Not Just Arterial Damage: Increased Incidence of Venous Thromboembolic Events in Cardiovascular Patients With Elevated Plasma Levels of Apolipoprotein CIII

Background Apolipoprotein CIII (apo CIII ) is a crucial player in triglyceride-rich lipoprotein metabolism, but may also act pleiotropically, provoking inflammatory responses and stimulating coagulation. Elevated apo CIII plasma levels have been associated with increased activity of coagulation factors. Since these features of prothrombotic diathesis are linked with venous thromboembolism ( VTE ), we hypothesized that apo CIII plays a role in VTE . Methods and Results We recorded nonfatal VTE events in 1020 patients (age 63.3\ub111.4 years; 29.1% women) with or without coronary artery disease (79.1% with coronary artery disease and 20.9% without coronary artery disease) during a long follow-up. Complete plasma lipid and apolipoproteins were available for all patients. Forty-five patients (4.4%) experienced nonfatal VTE events during a median follow-up period of 144 months. Apo CIII plasma concentration at enrollment was higher in patients with VTE compared with patients without VTE (12.2 [95% CI, 11.10-13.5] mg/dL vs 10.6 [95% CI, 10.4-10.9] mg/dL, respectively; P=0.011). Patients with apo CIII levels above the median value (10.6 mg/dL) exhibited an increased risk of VTE (incidence rate, 6.0 [95% CI , 4.0-8.0] vs 1.8 [95% CI, 0.7-2.9] VTE events/1000 person-years; unadjusted hazard ratio [ HR ], 3.42 [95% CI , 1.73-6.75]; P<0.001). This association was confirmed after adjustment for sex, age, coronary artery disease diagnosis, body mass index, hypertension, and anticoagulant treatment at enrollment ( HR , 2.66; 95% CI , 1.31-5.37 [ P=0.007]), with inclusion of lipid parameters in the Cox model (HR, 3.74; 95% CI , 1.24-11.33 [ P=0.019]), and even with exclusion of patients who died at follow-up ( HR, 3.92; 95% CI , 1.68-9.14 [ P=0.002]) or patients taking anticoagulants ( HR , 3.39; 95% CI , 1.72-6.69 [ P<0.001]). Conclusions Our results suggest that high plasma apo CIII concentrations may predict an increased risk of VTE in patients with cardiovascular disease

Laparoscopic surgery does not reduce the need for red blood cell transfusion after resection for colorectal tumour: a propensity score match study on 728 patients

Background: Patients with colorectal tumour often present with anaemia, and up to 60% will receive red blood cells (RBC) transfusion. Some evidence suggests a correlation between RBC transfusion and worse outcomes. Since laparoscopy minimizes intraoperative blood loss, we retrospectively investigated its role in reducing haemoglobin (Hb) drop and requirements for postoperative RBC transfusions. Methods: Patients were identified from consecutive cases undergone elective surgery for non-metastatic colorectal tumour between 2005 and 2019. Laparoscopic cases were matched 1:1 with open controls through propensity score matching (PSM). The main outcome measures were postoperative Hb drop and requirement for RBC. The secondary aim was evaluation of risk factors for postoperative RBC transfusions. Results: After application of PSM, 364 patients treated by laparoscopy were matched with 364 patients undergone open surgery. The two groups presented similar clinical and pathological characteristics, as well as comparable postoperative outcomes. 56 patients in the open group and 47 in the laparoscopic group required postoperative RBC (P = 0.395). No difference was observed in terms of mean number of RBC units (P = 0.608) or Hb drop (P = 0.129). Logistic regression analysis identified preoperative anaemia and occurrence of postoperative complications as relevant risk factors for postoperative RBC transfusion, while surgical approach did not prove statistically significant. Conclusion: Laparoscopy did not influence postoperative requirements for RBC transfusions after elective colorectal surgery. Preoperative anaemia and occurrence of postoperative complications represent the major determinants for postoperative transfusions after open as well as laparoscopic surgery

The role of Matriptase-2 during the early postnatal development in humans

Hepcidin is the hepatic peptide hormone, which regulates the systemic iron homeostasis by degrading the only cellular iron exporter ferroportin. The transmembrane serine protease matriptase-2 (MT-2, encoded by TMPRSS6) is a major hepcidin inhibitor and mutations in TMPRSS6 gene are responsible of inherited iron refractory iron deficiency anemia (IRIDA), characterized by hypochromic microcytic anemia, low transferrin saturation and inappropriate normal/high levels of hepcidin. In this study we retrospectively analyzed the hematological parameters in the (neo) perinatal period of IRIDA patients to understand the role of matriptase-2 at birth and during early development. We found that anemia is not present at birth and thus we inferred that it is absent also in utero but develops after the second month of life. Our results might have implications to better understand iron homeostasis during early development in IRIDA patients and indicate that Mt2 is dispensable during fetal and neonatal life in humans, consistent with the idea that the downregulation of hepcidin by Mt2 becomes effective only with the introduction of dietary iron