Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: clinical and immunological data of a phase I/II clinical trial

Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months. ECOG grade 2 toxicity was observed at the injection site. Eight out of 14 patients showed specific CD8+ T cells to at least one antigen. None of 4 patients vaccinated for compassionate use showed a CD8 activation. An OC patient who suffered from a lymph nodal recurrence, showed specific anti-ErbB2 CD8+ T cells in the bulky aortic lymph nodes suggesting homingof the activated T cells. Results confirm that peptide vaccination strategy is feasible, safe and well tolerated. In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments

Metformin-related lactic acidosis: is it a myth or an underestimated reality?

AbstractMetformin, belonging to a class of drugs called biguanides, is the recommended first-line treatment for overweight patients with type 2 diabetes mellitus. It has multiple mechanisms of action, such as reduction of gluconeogenesis, increases peripheral uptake of glucose, and decreases fatty acid oxidation. However, a potential serious complication, defined metformin-associated lactic acidosis (MALA), is related to increased plasma lactate levels, linked to an elevated plasma metformin concentrations and/or a coexistent condition altering lactate production or clearance. The mortality rate for MALA approaches 50% and metformin has been contraindicated in moderate and severe renal impairment, to minimize its potential toxic levels. Nevertheless, metformin prescription or administration, despite the presence of contraindications or precipitating factors for MALA, was a common topic highlighted in all reviewed papers. Routine assessment of metformin plasma concentration is not easily available in all l..

Compost and microbial biostimulant applications improve plant growth and soil biological fertility of a grass-based phytostabilization system

In this work, a grass-based phytoremediation system integrated with an organic amendment and biostimulants was evaluated for remediating contaminated sites. Plant growth and biological fertility were monitored to assess the efficacy of a vegetative cap used as a safety measure to reduce sanitary and environmental risks of industrially contaminated soils and soil-washing sludges. Both matrices were potentially contaminated with Pb and Zn with an ecological risk index from low to moderate. According to potentially toxic elements (PTEs) bioaccessibility tests, the exposure to the released fine particulate matter may cause serious risks to human beings, in particular to children. The grass mixture was well adapted to both the substrates and a low PTEs mobility was detected, thus, reducing the leaching risk to ground water sources. Compost addition augmented significantly nitrogenase reductase (nifH) and ammonia monooxygenase (amoA) gene expression abundance in both substrates. Furthermore, a positive interaction between compost fertilization and a Trichoderma-based biostimulant inoculation was recorded in sludges resulting in a significant stimulation of nitrogen-fixing and ammonia-oxidizing bacteria. The application of compost and biostimulant increased soil fertility and plant growth. Furthermore, there was a slight reduction in PTE bioaccessibility, thus, improving the efficiency of the phytostabilization, limiting the resuspension and dispersion of the health-risk soil particulate

Emergency contraception: an updated review

Emergency contraception is a common practice now. Many categories of drugs are marketed with modifications in dosage, in combination and even in the timing of administration. Recent re-analysis suggests that there is still no uniformity of opinion on the actual mechanism of action and this has often fueled the ethical controversy. This review analyzes the most common emergency contraception drugs: levonorgestrel, mifepristone and ulipristal acetate about their action underlining that the hormonal products, when used in emergency contraception, play different roles depending on the phase of the menstrual cycle during which they are administered.This review aims to examine rigorously the most accredited literature to verify if a evidence-based uniformity of opinions has been achieved about the biological effects of hormones administered after the sexual intercourse

Monoclonal Antibodies in Gynecological Cancer: A Critical Point of View

During the last decades, several improvements in treating gynecological malignancies have been achieved. In particular, target therapies, mostly monoclonal antibodies, have emerged as an attractive option for the treatment of these malignancies. In fact, various molecular-targeted agents have been developed for a variety of malignancies with the objective to interfere with a precise tumor associated receptor, essential for cancer cell survival or proliferation, blocking its function, of the cancer cells. Alternatively, monoclonal antibodies have been developed to block immune suppression or enhance functions of immune effector cells. So far, several monoclonal antibodies have been tested for clinical efficacy for the treatment of gynecological cancers. Antibodies against Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR) have been used in different neoplasms such as ovarian and cervical cancer. Catumazumab, a bivalent antibody against CD3 and EpCAM, is effective in the treatment of neoplastic ascites. Other antibodies are peculiar for specific cancer-associated antigen such as Oregovomab against CA125 or Farletuzumab against the folate receptor. Here we describe the preclinical and clinical experience gained up to now with monoclonal antibodies in tumors of the female genital tract and trace future therapeutic and research venues

Thiersch graft follow-up with narrow band imaging for acquired atresia of the external auditory canal: Canaloplasty with Thiersch graft versus vascularization evaluated with narrow band imaging

Acquired atresia of the external ear canal is a narrowing of the external ear canal (EAC) that appears obstructed by fibrous tissue or bone tissue. Acquired atresia has two different phases: wet and dry stage. Computed tomography (CT) scan may show a scan where soft tissue fills EAC. Treatment may be medical and/or surgical. The surgical treatment of choice is represented by canaloplasty with a skin-free flap. To our knowledge, no article has reported data on the analysis of vascularization of acquired atresia of the external ear canal and vascularization of skin flap during follow-up with narrow-band imaging. This study evaluated patients suffering from acquired atresia of the external auditory duct, treated surgically in our Department of Organi di Senso of Sapienza University, from 2017 to 2020. All patients underwent: anamnestic collection, physical examination, CT. Preoperative and postoperative otoendoscopic evaluation (1,3,6 and12 months) was performed with both cold white light endoscopic vision (CWL) and narrowband imaging (NBI). 17 patients were enrolled in the study. Preoperative otoendoscopic examination of WL showed stenosis with a diameter <75% and a tympanic membrane not viewable in all patients. At 12 months of follow-up, 94% of patients had no recurrence of external ear canal stenosis. 88% of patients had normal NBI light vascularization. Our study evaluated how NBI can be a superior method, compared to CWL, to assess the state of the flap and can be relevant in the decision-making process of a re-intervention

Acquired atresia of the external auditory canal and canaloplasty with Thiersch graft reconstruction: Outcomes and complications

Acquired atresia of the external auditory canal (EAC) is a rare disease characterized by otorrhea and progressive hearing loss. Clinically, it is differentiated into two stages: the wet stage and the dry stage. The dry stage does not respond to pharmacological treatment and has to be treated surgically. One surgical option is canaloplasty of the EAC with Thiersch graft reconstruction. This study aimed to report the follow-up outcomes (otomicroscopic signs and pure tone audiometry [PTA]) in patients with acquired atresia treated with this technique. Eighteen adult patients surgically treated for acquired atresia of the EAC between 2010 and 2020 were enrolled. All underwent canaloplasty with Thiersch graft reconstruction by one senior surgeon. Otomicroscopy and PTA results were evaluated before and after surgery. Postsurgical follow-up was performed at 1-3-6-12 months and then annually. Presurgical otomicroscopic examination revealed stenosis that occluded more than 75% of the EAC in all patients, and preoperative PTA showed conductive hearing loss in 89% of patients. However, postsurgical otomicroscopic examination showed that 94% of patients had a normal EAC diameter after one year, and only one patient had anterior blunting and recurrent atresia. In addition, postsurgical PTA evidenced a normal range in 89% of patients after one year. In conclusion, acquired atresia of the EAC is a troublesome disease usually associated with hearing loss. Therefore, treatment is chosen to resolve its symptoms. The results demonstrate evidence that canaloplasty with Thirsch graft may be a suitable surgical method considering the lower incidence of recurrence and the excellent hearing outcomes

Aneurysmal subarachnoid haemorrhage in pregnancy: a case series

Pregnancy is a recognized risk factor for aneurysmal subarachnoid hemorrhage (SAH). Headache is very frequent in normal pregnancy and it is a common sign shared between several intracranial diseases. We present a case series of 10 women in the third trimester of pregnancy admitted to our intensive care unit (ICU) with neurological signs and symptoms. 4 of these patients were diagnosed with SAH. Data in this study suggest that a timely diagnosis and an appropriate treatment is crucial for mother and baby