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.

The Combined Use of Fractional Urate and Potassium Excretion in the Diagnosis of Diuretic-Induced Hyponatremia.

Introduction Thiazide and loop-diuretics are among the most widely used drugs in the therapy of hypertension and chronic heart failure. Furthermore, hyponatremia is the most prevalent electrolyte imbalance affecting up to 25-30% of hospitalized patients while syndrome of inappropriate antidiuresis (SIAD) is involving approximately 35% of hyponatraemic inpatients. Clinical and laboratoristic algorithms support the differential diagnosis of hypotonic hyponatremia in actual guidelines of SIAD, but a potential bias is represented by the misleading clinical assessment of the extracellular volume status in diuretic-treated patients where the necessity of withdrawal of the therapy is mandatory. We investigated the role of fractional uric acid and potassium excretion (FEUA and FEK) in the differential diagnosis of hypotonic hyponatremia in SIAD and diuretic-treated patients. Methods Thirty-six SIAD, 30 thiazide-induced hyponatremia (TIH), and 32 diuretic-induced hyponatremia (DIH) patients were investigated calculating FEUA and FEK values in receiver operating characteristic (ROC) curve analysis to improve the diagnostic approach of hypotonic hyponatremia. Results The combination of the two investigated markers showed different significative results generating patterns useful to discriminate among the three different hyponatremic groups. Conclusion The fractional uric acid and potassium excretion could be considered as new markers in the diagnostic approach of hyponatremic diuretic-treated patients where classical algorithms could fail.

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.

The Role of Fractional Excretion of Uric Acid in the Differential Diagnosis of Hypotonic Hyponatraemia in Patients with Diuretic Therapy.

Hyponatraemia is the most common electrolyte imbalance found in hospital population and worldwide thiazide and loop-diuretics are among the most widely used drugs. Syndrome of inappropriate antidiuresis diagnosis (SIAD) is complicated in the presence of diuretic therapy due to the misleading clinical assessment of the extracellular volume status, and in order to make SIAD diagnosis it is often necessary to withdraw diuretic therapy. Our study aimed to investigate the diagnostic role of these alternative markers of volume status, serum uric acid (sUA) and fractional excretion of uric acid (FEUA), in hyponatraemic patients treated with different diuretic drugs. Eighty-nine patients were enrolled with the diagnosis of SIAD, diuretic-induced hyponatremia (DIH, treated with furosemide and potassium canrenoate) or thiazide-induced hyponatremia (TIH, treated with hydrochlorothiazide, metolazone or indapamide) and investigated with receiver operating characteristic analysis and a sensitivity test. Our results show that FEUA discriminated better than sUA between SIAD and DIH patients (area under curve 0.96, <0.001 vs. 0.88, <0.001) while it was a poor marker to discriminate between SIAD and TIH (0.65, NS vs. 0.67, NS). In conclusions, FEUA is an excellent marker to discriminate SIAD vs. sodium depleted patients treated with furosemide and/or potassium canrenoate while the diuretic withdrawal, beyond obtaining a serum Na normalization, is still mandatory for differential diagnosis of sodium depleted patients affected by thiazide-induced hyponatraemia.

Efficacy and Safety of Everolimus in Extrapancreatic Neuroendocrine Tumor: A Comprehensive Review of Literature.

BACKGROUND: Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs. PATIENTS AND METHODS: A systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary. RESULTS: The present study included 22 different publications, including 874 patients and 456 extrapancreatic NETs treated with everolimus. Nine different primary sites of extrapancreatic NETs were found. The median progression-free survival ranged from 12.0 to 29.9 months. The median time to progression was not reached in a phase II prospective study, and the interval to progression ranged from 12 to 36 months in 5 clinical cases. Objective responses were observed in 7 prospective studies, 2 retrospective studies, and 2 case reports. Stabilization of the disease was obtained in a high rate of patients, ranging from 67.4% to 100%. The toxicity of everolimus in extrapancreatic NETs is consistent with the known safety profile of the drug. Most adverse events were either grade 1 or 2 and easy manageable with a dose reduction or temporary interruption and only rarely requiring discontinuation. CONCLUSION: Treatment with everolimus in patients with extrapancreatic NETs appears to be a promising strategy that is safe and well tolerated. The use of this emerging opportunity needs to be validated with clinical trials specifically designed on this topic. IMPLICATIONS FOR PRACTICE: The present study reviewed all the available published data concerning the use of everolimus in 456 extrapancreatic neuroendocrine tumors (NETs) and summarized the current knowledge on the efficacy and safety of this drug, not yet approved except for pancreatic NETs. The progression-free survival rates and some objective responses seem promising and support the extension of the use of this drug. The site-by-site analysis seems to suggest that some subtypes of NETs, such as colorectal, could be more sensitive to everolimus than other primary NETs. No severe adverse events were usually reported and discontinuation was rarely required; thus, everolimus should be considered a valid therapeutic option for extrapancreatic NETs.

Autoimmune thyroid diseases and Helicobacter pylori: the correlation is present only in Graves's disease.

AIM: To investigate the correlation between autoimmune thyroid diseases (ATDs) and the prevalence of Cag-A positive strains of Helicobacter pylori (H. pylori) in stool samples. METHODS: Authors investigated 112 consecutive Caucasian patients (48 females and 4 males with Graves' disease and 54 females and 6 males with Hashimoto's thyroiditis HT), at their first diagnosis of ATDs. Authors tested for H. pylori in stool samples using an amplified enzyme immunoassay and Cag-A in serum samples using an enzyme-linked immunoassay method (ELISA). The results were analyzed using the two-sided Fisher's exact test and the respective odds ratio (OR) was calculated. RESULTS: A marked correlation was found between the presence of H. pylori (P ≤ 0.0001, OR 6.3) and, in particular, Cag-A positive strains (P ≤ 0.005, OR 5.3) in Graves' disease, but not in Hashimoto's thyroiditis, where authors found only a correlation with Cag-A strains (P ≤ 0.005, OR 8.73) but not when H. pylori was present. CONCLUSION: The marked correlation between H. pylori and Cag-A, found in ATDs, could be dependent on the different expression of adhesion molecules in the gastric mucosa.

Identification of a correlation between Helicobacter pylori infection and Graves' disease.

BACKGROUND: Viral and bacterial antigens have been suspected to be able to mimic the antigenic profile of the thyroid cell membrane and to play an important role in the onset of the autoimmune diseases, such as Graves' disease and Hashimoto thyroiditis. The Helicobacter pylori infection is worldwide diffused and is present in the developed countries up to 50% of the population. The presence of the cytotoxin-associated gene A antigens identifies the most virulent strains of the bacterium. Previous studies have demonstrated the possible correlation between the Helicobacter pylori and Hashimoto's thyroiditis but these results are controversial. AIMS: We studied the prevalence rate of this bacterium in the Graves' disease and two selected subgroups such as the hyperthyroid patients, at the first time of diagnosis, and the euthyroid methimazole-treated patients. MATERIALS AND METHODS: We analyzed Helicobacter pylori in fresh stool samples with an enzyme immunoassay method and the presence of cytotoxin-associated gene A antigens with a serological test. RESULTS: Our results show that a significative increased rate of prevalence is present in Graves' patients, when the disease is ongoing, with an overall prevalence of the strains expressing the cytotoxin-associated gene A antigens compared to the control group. CONCLUSIONS: The association between the Helicobacter pylori and Graves' disease suggests a possible role of this bacterium in the onset and/or the maintenance of the disease.