Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: An observational cohort study

Background: Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. Methods: We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann-Whitney test. Trends over time were tested with the Kruskal-Wallis analysis. Results: Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 μg/L, IQR 69 μg/L at admission; median 73 μg/L, IQR 56 μg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 μg/L; IQR 1285 μg/L) to days 3 to 6 (median 6820 μg/L; IQR 6619 μg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay. Conclusions: The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology

Vitamin D deficiency and tumor aggressiveness in gastroenteropancreatic neuroendocrine tumors

Purpose: Data regarding vitamin D status in patients affected by gastroenteropancreatic (GEP) neuroendocrine tumor (NET) are limited and often showing contrasting results. The aim of the study was to evaluate the incidence of vitamin D deficiency (<20 ng/mL) in GEP-NET patients and compare the 25-hydroxyvitamin D (25(OH)D) levels with clinicopathological parameters and clinical outcome. Methods: A retrospective cross-sectional study including 75 low grade (G1-G2) GEP-NETs and 123 healthy controls matched for age, sex, and body mass index, was performed. Results: GEP-NET patients had significantly lower 25(OH)D levels compared to controls (17.9 ± 7.8 vs 24.2 ± 7.7 ng/mL, p < 0.0001). Ileal NETs were associated to lower 25(OH)D levels compared to other primary tumor sites (p = 0.049) and small bowel resection posed a significant increased risk of severe vitamin D deficiency (OR = 2.81, 95% CI = 1.25–3.37, p = 0.018). No correlation with somatostatin analogs treatment was found. 25(OH)D levels were significantly lower in G2 compared to G1 GEP-NETs (15.6 ± 7.8 vs 19.9 ± 7.4 ng/mL, p = 0.016) and in patients with progressive disease (12.6 ± 5.7 ng/mL) compared to those with stable disease (mean 21.5 ± 8.2 ng/mL, p = 0.001) or tumor free after surgery (19.6 ± 7.3 ng/mL, p = 0.002). Patients with vitamin D deficiency and insufficiency had shorter progression-free survival compared to those with sufficiency (p = 0.014), whereas no correlation was found with disease-specific survival. Conclusions: Vitamin D deficiency is highly prevalent among GEP-NETs and could be associated with high tumor grade and disease progression. Therefore, the monitoring of 25(OH)D levels is relevant in these patients and vitamin D supplementation should be considered in the management of GEP-NET patients with vitamin D deficiency or insufficiency

From intensive care to step-down units: Managing patients throughput in response to COVID-19

Quality problem or issue: The on-going COVID-19 pandemic may cause the collapse of healthcare systems because of unprecedented hospitalization rates. Initial assessment: A total of 8.2 individuals per 1000 inhabitants have been diagnosed with COVID-19 in our province. The hospital predisposed 110 beds for COVID-19 patients: On the day of the local peak, 90% of them were occupied and intensive care unit (ICU) faced unprecedented admission rates, fearing system collapse. Choice of solution: Instead of increasing the number of ICU beds, the creation of a step-down unit (SDU) close to the ICU was preferred: The aim was to safely improve the transfer of patients and to relieve ICU from the risk of overload. Implementation: A nine-bed SDU was created next to the ICU, led by intensivists and ICU nurses, with adequate personal protective equipment, monitoring systems and ventilators for respiratory support when needed. A second six-bed SDU was also created. Evaluation: Patients were clinically comparable to those of most reports from Western Countries now available in the literature. ICU never needed supernumerary beds, no patient died in the SDU, and there was no waiting time for ICU admission of critical patients. SDU has been affordable from human resources, safety and economic points of view. Lessons learned: COVID-19 is like an enduring mass casualty incident. Solutions tailored on local epidemiology and available resources should be implemented to preserve the efficiency and adaptability of our institutions and provide the adequate sanitary response

Infection-Related Ventilator-Associated Complications in Critically Ill Patients with Trauma: A Retrospective Analysis

Background: Trauma is a leading cause of death and disability. Patients with trauma undergoing invasive mechanical ventilation (IMV) are at risk for ventilator-associated events (VAEs) potentially associated with a longer duration of IMV and increased stay in the intensive care unit (ICU). Methods: We conducted a retrospective cohort study aimed to evaluate the incidence of infection-related ventilator-associated complications (IVACs), possible ventilator-associated pneu- monia (PVAP), and their characteristics among patients experiencing severe trauma that required ICU admission and IMV for at least four days. We also determined pathogens implicated in PVAP episodes and characterized the use of antimicrobial therapy. Results: In total, 88 adult patients were included in the main analysis. In this study, we observed that 29.5% of patients developed a respiratory infection during ICU stay. Among them, five patients (19.2%) suffered from respiratory infections due to multi-drug resistant bacteria. Patients who developed IVAC/PVAP presented lower total GCS (median value, 7; (IQR, 9) vs. 12.5, (IQR, 8); p = 0.068) than those who did not develop IVAC/PVAP. Conclusions: We observed that less than one-third of trauma patients fulfilling criteria for ventilator associated events developed a respiratory infection during the ICU stay

Epigenome-wide association study in hepatocellular carcinoma : Identification of stochastic epigenetic mutations through an innovative statistical approach

Hepatocellular carcinoma (HCC) results from accumulation of both genetic and epigenetic alterations. We investigated the genome-wide DNA methylation profile in 69 pairs of HCC and adjacent non-cancerous liver tissues using the Infinium HumanMethylation 450K BeadChip array. An innovative analytical approach has been adopted to identify Stochastic Epigenetic Mutations (SEMs) in HCC.HCC and peritumoral tissues showed a different epigenetic profile, mainly characterized by loss of DNA methylation in HCC. Total number of SEMs was significantly higher in HCC tumor (median: 77,370) than in peritumoral (median: 5,656) tissues and correlated with tumor grade. A significant positive association emerged between SEMs measured in peritumoral tissue and hepatitis B and/or C virus infection status. A restricted number of SEMs resulted to be shared by more than 90% of HCC tumor samples and never present in peritumoral tissue. This analysis allowed the identification of four epigenetically regulated candidate genes (AJAP1, ADARB2, PTPRN2, SDK1), potentially involved in the pathogenesis of HCC.In conclusion, HCC showed a methylation profile completely deregulated and very far from adjacent non-cancerous liver tissues. The SEM analysis provided valuable clues for further investigations in understanding the process of tumorigenesis in HCC

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

The tumor dynamism is the dark matter of the ngs galaxy: How to understand it?

: Since its discovery, there has been a great enthusiasm around NGS (next generation sequencing) technology due to extensive (from restricted gene panels to entire genomes) and rapid (few hours) DNA sequencing [...]