Use of oral glutamine in radiation-induced adverse effects in patients with thoracic and upper aerodigestive malignancies: Results of a prospective observational study.

Cancer growth in host tissues features glutamine (gln) depletion over time, decreasing epithelial cells' optimal functioning. In addition, radiotherapy (RT) and/or chemotherapy (CT) cause damage to normal tissues, probably enhanced by this depletion. The present study prospectively examined the effect of gln supplementation on 72 patients with thoracic and upper aerodigestive malignancies (T&UAM) treated with sequential or concurrent RT-CT or RT alone. All patients received prophylactic gln powder 15 g bid for the full duration of treatment. The severity of acute radiation toxicities was graded according to the RT Oncology Group/European Organization for Research and Treatment of Cancer criteria. Primary endpoints were the incidence of grade >2 toxicities, weight loss and requirement for analgesics, and the secondary endpoint was the association of the length of irradiated esophagus from treatment planning with the use of opioids. The incidence of adverse effects was as follows: Grade >2 stomatitis, 25.0%; esophagitis, 60.5%; dysphagia, 54.2%; pain, 25.4%; mycosis, 40.8%. Stomatitis grade >2 was more frequent in patients with head and neck tumors (P<0.001) and in those with prior surgery (P<0.001). Esophagitis (P=0.020) and dysphagia (P=0.008) grade >2 were more frequent in patients with concurrent RT-CT. Regarding analgesics, 9.9% of patients received no pain treatment, 56.3% received simple analgesic therapy and 33.8% opioids. Patients on opioid therapy had a greater mean length of irradiated esophagus (P=0.024) or length >12 cm (P=0.018). In 54.2% of patients, weight loss was observed, particularly with concurrent RT-CT (P=0.007). Thus, the use of oral gln may have an important role in reducing acute radiation toxicities and weight loss, and in lowering the requirement for analgesics in patients with T&UAM. Further randomized trials are required to identify the appropriate gln dose, duration of treatment and precise radiation dosimetric parameters in this group of patients. The present clinical trial was retrospectively registered in the ClinicalTrials.gov Protocol Registration and Results System (registration no. NCT05054517/22-09-2021).

Immune response (IgG) following full inoculation with BNT162b2 COVID­19 mRNA among healthcare professionals.

Soon after the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) pandemic in December, 2019, numerous research teams, assisted by vast capital investments, achieved vaccine development in a fraction of time. However, almost 8 months following the initiation of the European vaccination programme, the need for prospective monitoring of the vaccine­induced immune response, its determinants and related side­effects remains a priority. The present study aimed to quantify the immune response following full vaccination with the BNT162b2 coronavirus disease 2019 (COVID­19) mRNA vaccine by measuring the levels of immunoglobulin G (IgG) titers in healthcare professionals. Moreover, common side­effects and factors associated with IgG titers were identified. For this purpose, blood samples from 517 individuals were obtained and analysed. Blood sampling was performed at a mean period of 69.0±23.5 days following the second dose of the vaccine. SARS­CoV­2 IgG titers had an overall mean value of 4.23±2.76. Females had higher titers than males (4.44±2.70 and 3.89 ±2.84, respectively; P=0.007), while non­smokers had higher titers than smokers (4.48±2.79 and 3.80±2.64, respectively; P=0.003). An older age was also associated with lower antibody titers (P<0.001). Moreover, the six most prevalent adverse effects were pain at the injection site (72.1%), generalized fatigue (40.5%), malaise (36.3%), myalgia (31,0%), headache (25.8%) and dizziness/weakness (21.6%). The present study demonstrated that the immune response after receiving the BNT162b2 COVID­19 mRNA vaccine is dependent on various modifiable and non­modifiable factors. Overall, the findings of the present study highlight two key aspects of the vaccination programs: First, the need for prospective immunosurveillance studies in order to estimate the duration of immunity, and second, the need to identify those individuals who are at a greater risk of developing low IgG titers in order to evaluate the need for a third dose of the vaccine.

Targeting vulnerable atherosclerotic plaque via PET-tracers aiming at cell-surface overexpression of somatostatin receptors.

Cardiovascular disease (CD) is the leading cause of death in the developed world, with major atherothrombotic events, being mainly attributed to the rupture of unstable, vulnerable atherosclerotic lesions, leading to blood flow obstruction. Since unstable atherosclerotic plaques frequently do not cause hemodynamically significant blood flow restriction, conventional stress imaging tests cannot depict the vulnerable, high-risk for rupture atherosclerotic lesions. Therefore, molecular imaging techniques targeting specific pathophysiologic features related to atherosclerotic plaque rupture mechanism, hold promise for precise and individualized treatment strategies of CD. In the current report, we describe in a patient diagnosed with pancreatic neuroendocrine tumor, the selective uptake of 68Ga-DOATATE by an atherosclerotic lesion in the thoracic aorta. This data indicates that 68Ga-DOTATATE, which is a positron emitting tomography tracer, targeting the recruitment of macrophages taking place in the vulnerable plaque, could potentially serve as an imaging probe for the detection of high-risk, prone to rupture plaques.

A dissection of SARS­CoV2 with clinical implications (Review).

We are being confronted with the most consequential pandemic since the Spanish flu of 1918­1920 to the extent that never before have 4 billion people quarantined simultaneously; to address this global challenge we bring to the forefront the options for medical treatment and summarize SARS­CoV2 structure and functions, immune responses and known treatments. Based on literature and our own experience we propose new interventions, including the use of amiodarone, simvastatin, pioglitazone and curcumin. In mild infections (sore throat, cough) we advocate prompt local treatment for the naso­pharynx (inhalations; aerosols; nebulizers); for moderate to severe infections we propose a tried­and­true treatment: the combination of arginine and ascorbate, administered orally or intravenously. The material is organized in three sections: i) Clinical aspects of COVID­19; acute respiratory distress syndrome (ARDS); known treatments; ii) Structure and functions of SARS­CoV2 and proposed antiviral drugs; iii) The combination of arginine­ascorbate.