An Attempted Suicide with Copper Sulphate injected intravenously:Pathopsysiology and Therapy about a case report

Acute copper sulphate poisoning is an unusual event, rarely following parenteral exposure, complicated by toxicological effects as haemolytic anaemia, methaemoglobinaemia , hepato-renal damage and acute rhabdomyolysis. Currently, the therapeutic management ignores unique classes of evidence and is mainly based on supportive and chelation therapies. Case details. This case report describes acute copper sulphate poisoning in a 37-year-old man who attempted suicide by self-injecting an unknown amount of copper sulphate. Within three days the patient developed severe intravascular haemolysis and rhabdomyolysis. Initial therapy relied on intensive supportive care with fluids administration, electrolyte correction and packed red blood cells transfusion. The D-penicillamine (30 mg/Kg/day per os) was prescribed as chelation therapy by the poison control centre. The N-acetilcysteine and ascorbic acid were administered to prevent further oxidative stress. Later on, two sessions of therapeutic plasma exchange were performed in order to support the drug therapy. Haemolysis and rhabdomyolysis reversed throughout the hospital stay. Discussion. In this case the antidotic and antioxidant therapy resulted effective to reverse haemolysis and rhabdomyolysis and to prevent hepatic and renal damage. Moreover, this case underlies that therapeutic plasma exchange should be considered as an additive measure to undertake since the earlier stages of the emergency intervention. Acute copper sulphate poisoning is an event complicated by toxicological effects: haemolytic anaemia, methaemoglobinaemia, hepato-renal damage, acute rhabdomyolysis. The therapeutic management ignores unique classes of evidence and is based on supportive and chelation therapies. In this case: i) the antidotic and antioxidant therapy resulted effective to reverse haemolysis and rhabdomyolysis and to prevent hepatic and renal damage, ii) therapeutic plasma exchange should be considered as an additive measure to undertake

IMMU-01. TEM-GBM: AN OPEN-LABEL, PHASE I/IIA DOSE-ESCALATION STUDY EVALUATING THE SAFETY AND EFFICACY OF GENETICALLY MODIFIED TIE-2 EXPRESSING MONOCYTES TO DELIVER IFN-A WITHIN GLIOBLASTOMA TUMOR MICROENVIRONMENT

Abstract Temferon is a macrophage-based treatment relying on ex-vivo transduction of autologous HSPCs to express immune-payloads within the TME. Temferon targets the immune-modulatory molecule IFN-a, to a subset of tumor infiltrating macrophages known as Tie-2 expressing macrophages (TEMs) due to the Tie2 promoter and a post-transcriptional regulation layer represented by miRNA-126 target sequences. As of 31st May 2021, 15-patients received Temferon (D+0) with follow-up of 3 – 693 days. After conditioning neutrophil and platelet engraftment occurred at D+13 and D+13.5, respectively. Temferon-derived differentiated cells, as determined be the number of vector copy per genome, were found within 14 days post treatment and persisted albeit at lower levels up to 18-months. Very low concentrations of IFN-a in the plasma (8.7 pg/ml-D+30) and in the CSF (1.6 pg/ml-D+30) were detected, suggesting tight regulation of transgene expression. Five-deaths occurred at D+322, +340, +402, +478 and +646 due to PD, and one at D+60 due to complications following the conditioning regimen. Eight-patients had progressive disease (range: D-11 to +239) as expected for this tumor type. SAEs include GGT elevation (possibly related to Temferon) and infections, venous thromboembolism, brain abscess, hemiparesis, seizures, anemia and general physical condition deterioration, compatible with ASCT, concomitant medications and PD. Four-patients underwent 2ndsurgery. Recurrent tumors had gene-marked cells and increased expression of ISGs compared to first surgery, indicative of local IFNa release by TEMs. In one patient, a stable lesion had a higher proportion of T cells and TEMs within the myeloid infiltrate and an increased ISGs than in the progressing lesion, detected in the same patient. Tumor-associated clones expanded in the periphery. TME characterization by scRNA and TCR-sequencing is ongoing. To date, Temferon is well tolerated, with no DLTs identified. The results provide initial evidence of Temferon potential to activate the immune system of GBM patients, as predicted by preclinical studies

Attempted suicide with intravenous copper sulphate: a case report

Acute Copper Sulphate Poisoning (ACuSP) usually results from oral ingestion with suicidal purpose, rarely from parenteral exposure: only few cases of parenteral ACuSP have been reported. Case report: a 37-year-old man was admitted at ED three hours after an attempted suicide by self-injecting intravenously an unknown amount of a copper sulfate solution. The patient had a history of heroin and cocaine abuse. At the admission, he was conscious, GCS 15, T 36.5°C, RR 18 breaths/min, SpO2 96% on room air, BP 105/75 mmHg, HR 120 beats/min. He presented tremors and diffuse myalgia. Biochemical tests were normal. One day later, serum copper levels reached 263 μ/dL (normal range 70-140 μ/dL). On day 3, he was oriented and febrile (T 38°C). Physical examination revealed pallor, jaundice, brown to red urines, signs of extravasation by the antecubital area of both arms. He was complaining epigastric pain. Laboratory findings showed normochromic normocytic anaemia (Hb 7.40 g/dL) with signs of intravascular haemolysis, methaemoglobin 6.3% and rhabdomyolysis. The patient received fluids therapy, electrolyte correction, and 4 units of RBC transfusion. N-acetilcysteine (150 mg/Kg over 120 minutes + 300 mg/Kg/day) and D-penicillamine (30 mg/Kg/day per os) were started. Piperacillin/tazobactam and clindamycin were administered for peri-injection cellullitis. As critical condition was persisting, Therapeutic Plasma Exchange (TPE) was performed on day 5 and 6. On day 7 he was transferred to the ICU, then to the surgery unit for wounds toilet. On day 12 he was moved to the psychiatric unit, on day 13 D-penicillamine was discontinued due to increasing liver function tests. On day 32 he was discharged asymptomatic with normal laboratory values. ACuSP is uncommon and insidious. Clinical picture is mainly characterized by massive haemolysis associated with slight extracellular methaemoglobin. The management is symptomatic and supportive. Chelation therapy is safe and effective. Haemodialysis is indicated only in case of persistent renal failure. The TPE should be considered as an addictive measure

Early decrease of oxidative stress by non-invasive ventilation in patients with acute respiratory failure

Oxidative stress plays an important role in chronic respiratory diseases where the use of non-invasive ventilation seems to reduce the oxidative damage. Data on acute respiratory failure are still lacking. The aim of the study is to investigate the interplay between oxidative stress and acute respiratory failure, and the role of non-invasive ventilation in this setting. We enrolled 60 patients suffering from acute respiratory failure (PaO2/FiO2 ratio <300): 30 consecutive patients treated with non-invasive ventilation and 30 consecutive patients treated with conventional oxygen therapy. Serum levels of soluble Nox2-derived peptide (sNOX2-dp), a marker of NADPH-oxidase activation, and 8-iso-PGF2α and H2O2, markers of oxidative stress, were evaluated at baseline and after 3 h of treatment. At baseline, higher values of sNOX2-dp, 8-iso-PGF2α and H2O2 are associated with lower values of PaO2/FiO2 ratio (p < 0.001). After 3 h, serum levels of sNOX2-dp, H2O2, and 8-iso-PGF2α significantly decrease in patients treated with non-invasive ventilation, but not in patients treated with conventional oxygen therapy. Delta changes of oxidative stress parameters correlate inversely with the delta changes of PaO2/FiO2 (R = -0.623, p < 0.001 for sNOX2-dp; R = -0.428, p < 0.001 for H2O2; R = -0.548, p < 0.001 for 8-iso-PGF2α). In the acute respiratory failure setting, treatment with non-invasive ventilation reduces the levels of oxidative stress in the first hours. This reduction is associated with an improvement of PaO2/FiO2 ratio as well as in a reduction of NADPH-oxidase activity

qSOFA as a new community-acquired pneumonia severity score in the emergency setting

Background: Quick Sequential Organ Failure Assessment (qSOFA) score is a bedside prognostic tool for patients with suspected infection outside the intensive care unit (ICU), which is particularly useful when laboratory analyses are not readily available. However, its performance in potentially septic patients with community-acquired pneumonia (CAP) needs to be examined further, especially in relation to early outcomes affecting acute management. Objective: First, to compare the performance of qSOFA and CURB-65 in the prediction of mortality in the emergency department in patients presenting with CAP. Second, to study patients who required critical care support (CCS) and ICU admission. Methods: Between January and December 2017, a 1-year retrospective observational study was carried out of adult (≥18 years old) patients presenting to the emergency department (ED) of our hospital (Rome, Italy) with CAP. The accuracy of qSOFA, qSOFA-65 and CURB-65 was compared in predicting mortality in the ED, CCS requirement and ICU admission. The concordance among scores ≥2 was then assessed for 30-day estimated mortality prediction. Results: 505 patients with CAP were enrolled. Median age was 71.0 years and mortality rate in the ED was 4.7%. The areas under the curve (AUCs) of qSOFA-65, CURB-65 and qSOFA in predicting mortality rate in the ED were 0.949 (95% CI 0.873 to 0.976), 0.923 (0.867 to 0.980) and 0.909 (0.847 to 0.971), respectively. The likelihood ratio of a patient having a qSOFA score ≥2 points was higher than for qSOFA-65 or CURB-65 (11 vs 7 vs 6.7). The AUCs of qSOFA, qSOFA-65 and CURB-65 in predicting CCS requirement were 0.862 (95% CI 0.802 to 0.923), 0.824 (0.758 to 0.890) and 0.821 (0.754 to 0.888), respectively. The AUCs of qSOFA-65, qSOFA and CURB-65 in predicting ICU admission were 0.593 (95% CI 0.511 to 0.676), 0.585 (0.503 to 0.667) and 0.570 (0.488 to 0.653), respectively. The concordance between qSOFA-65 and CURB-65 in 30-day estimated mortality prediction was 93%. Conclusion: qSOFA is a valuable score for predicting mortality in the ED and for the prompt identification of patients with CAP requiring CCS. qSOFA-65 may further improve the performance of this useful score, showing also good concordance with CURB-65 in 30-day estimated mortality prediction

Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB 1.0): development and normative data

Background: Neuropsychological testing plays a cardinal role in the diagnosis and monitoring of Alzheimer's disease. A major concern is represented by the heterogeneity of the neuropsychological batteries currently adopted in memory clinics and healthcare centers. The current study aimed to solve this issue. Methods: Following the initiative of the University of Washington's National Alzheimer's Coordinating Center (NACC), we presented the Italian adaptation of the Neuropsychological Test Battery of the Uniform Data Set (I-UDSNB). We collected data from 433 healthy Italian individuals and employed regression models to evaluate the impact of demographic variables on the performance, deriving the reference norms. Results: Higher education and lower age were associated with a better performance in the majority of tests, while sex affected only fluency tests and Digit Span Forward. Conclusions: The I-UDSNB offers a valuable and harmonized tool for neuropsychological testing in Italy, to be used in clinical and research settings