Adjunctive use of oral MAF is associated with no disease progression or mortality in hospitalized patients with COVID-19 pneumonia: The single-arm COral-MAF1 prospective trial.

Based on a growing body of evidence that a dysregulated innate immune response mediated by monocytes/macrophages plays a key role in the pathogenesis of COVID-19, a clinical trial was conducted to investigate the therapeutic potential and safety of oral macrophage activating factor (MAF) plus standard of care (SoC) in the treatment of hospitalized patients with COVID-19 pneumonia. Ninety-seven hospitalized patients with confirmed COVID-19 pneumonia were treated with oral MAF and a vitamin D3 supplement, in combination with SoC, in a single-arm, open label, multicentre, phase II clinical trial. The primary outcome measure was a reduction in an intensive care unit transfer rate below 13% after MAF administration. At the end of the study, an additional propensity score matching (PSM) analysis was performed to compare the MAF group with a control group treated with SoC alone. Out of 97 patients treated with MAF, none needed care in the ICU and/or intubation with mechanical ventilation or died during hospitalization. Oxygen therapy was discontinued after a median of nine days of MAF treatment. The median length of viral shedding and hospital stay was 14 days and 18 days, respectively. After PSM, statistically significant differences were found in all of the in-hospital outcomes between the two groups. No mild to serious adverse events were recorded during the study. Notwithstanding the limitations of a single-arm study, which prevented definitive conclusions, a 21-day course of MAF treatment plus SoC was found to be safe and promising in the treatment of hospitalized adult patients with COVID-19 pneumonia. Further research will be needed to confirm these preliminary findings.

Successful Treatment of Iron Deficiency Anemia with Ferric Carboxymaltose in an Elderly Patient with Multiple Comorbidities and COVID-19.

Anemia is frequently associated with older age and comorbidities. Also, anemia is a frequent finding in patients hospitalized for Coronavirus infectious disease 2019 (COVID-19), where it has been associated with poor outcomes. Management of anemia is thus crucial in this setting. We present the case of an elderly woman with chronic iron deficiency anemia and multiple comorbidities, hospitalized for COVID-19, whose iron deficiency was successfully treated with ferric carboxymaltose. Hemoglobin and iron stores were replenished, and transferrin saturation increased to average values. Ferric carboxymaltose was well tolerated, and there were no safety concerns. The patient recovered from COVID-19 was discharged 25 days after admission.

A Triad of Ketoacidosis, Hypertriglyceridemia, and Acute Pancreatitis Associated With Sugar-Sweetened Soft Drinks Abuse in a Caucasian Patient With Undiagnosed Type 2 Diabetes Mellitus.

A 24-year-old obese Caucasian male, without relevant anamnesis, who was admitted to the ER presented with abdominal pain, nausea and vomiting, hyperglycemia, and diabetic ketoacidosis (DKA). The diagnosis of acute pancreatitis (AP) was supported by increased serum levels of triglycerides and lipase associated with abdominal CT scans. The patient was treated for five days with IV regular insulin, hydration, electrolytes replacement, and statin/fibrate therapy with clinical improvement. Some 10% hemoglobin A1c value, normal C-peptide level and negative glutamic acid decarboxylase (GAD-65), and islet cell autoantibodies suggested the diagnosis of a new-onset type 2 diabetes mellitus (DM) presenting with an uncommon triad of DKA and hypertriglyceridemia (HTG)-induced AP. Anamnestic history suggested that DKA was dependent on sugar-sweetened soft drinks abuse (soft drink ketosis), a clinical association more frequent in Asian than in Western patients.

Different involvement of autophagy in human malignant glioma cell lines undergoing irradiation and temozolomide combined treatments.

Glioblastoma (GB) has a poor prognosis, despite current multimodality treatment. Beside surgical resection, adjuvant ionizing radiation (IR) combined with Temozolomide (TMZ) drug administration is the standard therapy for GB. This currently combined radio-chemotherapy treatment resulted in glial tumor cell death induction, whose main molecular death pathways are still not completely deciphered. In this study, the autophagy process was investigated, and in vitro modulated, in two different GB cell lines, T98G and U373MG (known to differ in their radiosensitivity), after IR or combined IR/TMZ treatments. T98G cells showed a high radiosensitivity (especially at low and intermediate doses), associated with autophagy activation, assessed by Beclin-1 and Atg-5 expression increase, LC3-I to LC3-II conversion and LC3B-GFP accumulation in autophagosomes of irradiated cells; differently, U373MG cells resulted less radiosensitive. Autophagy inhibition, using siRNA against BECN1 or ATG-7 genes, totally prevented decrease in viability after both IR and IR/TMZ treatments in the radiosensitive T98G cells, confirming the autophagy involvement in the cytotoxicity of these cells after the current GB treatment, contrary to U373MG cells. However, rapamycin-mediated autophagy, that further radiosensitized T98G, was able to promote radiosensitivty also in U373MG cells, suggesting a role of autophagy process in enhancing radiosensitivity. Taken together, these results might enforce the concept that autophagy-associated cell death might constitute a possible adjuvant therapeutic strategy to enhance the conventional GB treatment.