Calcium,Magnesium, and Zinc Supplementation during Pregnancy: The Additive Value of Micronutrients on Maternal Immune Response after SARS-CoV-2 Infection

Magnesium may contribute to the immune response during and after SARS-CoV-2 infection by acting as a cofactor for immunoglobulin production and other processes required for T and B cell activity. Considering magnesium as a recommended dietary supplement during pregnancy and the possible role of magnesium deficiency in COVID-19 and its complications, the current study sought to determine the effect of magnesium and magnesium-containing nutritional supplements on the immune response following SARS-CoV-2 infection in pregnant women, as well as to observe differences in pregnancy outcomes based on the supplements taken during pregnancy. The study followed a cross-sectional design, where patients with a history of SARS-CoV-2 infection during their pregnancy were surveyed for their preferences in nutritional supplementation and their profile compared with existing records from the institutional database. A cohort of 448 pregnant women with COVID-19 during 22 months of the pandemic was assembled, out of which 13.6% took a magnesium-only supplement, and 16.5% supplemented their diet with a combination of calcium, magnesium, and zinc. Around 60% of patients in the no-supplementation group had the SARS-CoV-2 anti-RBD lower than 500 U/mL, compared with 50% in those who took magnesium-based supplements. A quantity of magnesium >450 mg in the taken supplements determined higher levels of antibody titers after COVID-19. Low magnesium dosage (<450 mg) was an independent risk factor for a weak immune response (OR-1.25, p-value = 0.003). The observed findings suggest supplementing the nutritional intake of pregnant women with magnesium-based supplements to determine higher levels of SARS-CoV-2 anti-RBD antibodies, although causality remains unclear.     

Gamma Irradiation and Ag and ZnO Nanoparticles Combined Treatment of Cotton Textile Materials

In this work, cotton textile materials were impregnated by immersion with three different nanocomposites: Ag/chitosan, Ag/polyvinylpyrrolidone, and ZnO/polyvinylpyrrolidone and irradiated with a ⁶⁰Co gamma source. After the nanoparticles impregnation, the cotton materials were irradiated in a dry and wet state at 5 and 20 kGy radiation doses. The following methods were used for the characterization of the obtained cotton materials to reveal the modification of the textile materials: Fourier transform infrared-attenuated total reflection spectroscopy (FTIR-ATR) and thermogravimetry (TG). The obtained materials have good antibacterial properties. The microbiological tests have shown the best material results for the gamma irradition and Ag nanoparticles combined treatment. The objective was to create a more environmentally friendly approach for textile functionalization by eliminating toxic chemicals-based technology and replacing it with the eco-friendlier gamma technology.     

Regional cardioprotection by subselective intracoronary nifedipine is not due to enhanced collateral flow during coronary angioplasty

Twelve patients with proximal stenosis of the left anterior descending artery, normal myocardial wall motion but without angiographically demonstrable collateral circulation, were studied during transluminal occlusion. Prior to the first transluminal occlusion before crossing the lesion with the balloon, patients were randomly given 0.2 mg nifedipine or its solvent in the left mainstem. The same dose was repeated via the balloon catheter, positioned across the lesion, immediately prior to the second transluminal occlusion. In all patients great cardiac venous flow and ST-elevation were monitored during and after each transluminal occlusion. The lactate extraction ratio A-GCV/A (A = arterial, GCV = great cardiac vein) was determined prior to the angioplasty procedure, 10-15 seconds after each transluminal occlusion and 10 minutes after the third transluminal occlusion. Great cardiac venous flow rose significantly to an average of 160% of basal flow when nifedipine was administered into the mainstem before the angioplasty procedure while its solvent had no effect. During each transluminal occlusion, great cardiac venous flow diminished on average by 30% in those who received nifedipine and by 28% in those who received only its solvent. This difference was statistically not significant. After angioplasty great cardiac venous flow was slightly, but not significantly, increased in both groups with respect to basal flow (104% resp. 120% of control). Patients who received nifedipine in the post-stenotic area just before the second transluminal occlusion, had significantly lower lactate production, measured immediately after the transluminal occlusion compared with the patients who received only its solvent (P less than 0.01). The ST-elevation during the second transluminal occlusion was significantly lower in the nifedipine group (0.1 mm in nifedipine group versus 1.4 mm in solvent group; P less than 0.05, unpaired t-test). Nifedipine given intracoronary in the post-stenotic area just before coronary angioplasty reduces lactate release and electrocardiographic signs of myocardial ischemic injury. This regional cardioprotective effect seems not due to an enhanced collateral flow, but to a regional cardioplegic effect, which precedes the ischemic event.     

Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease

1. Download : Download high-res image (262KB)
2. Download : Download full-size image

     

Imaging the effective networks associated with cortical function through intracranial high‐frequency stimulation

Direct electrical stimulation (DES) is considered to be the gold standard for mapping cortical function. A careful mapping of the eloquent cortex is key to successful resective or ablative surgeries, with a minimal postoperative deficit, for treatment of drug‐resistant epilepsy. There is accumulating evidence suggesting that not only local, but also remote activations play an equally important role in evoking clinical effects. By introducing a new intracranial stimulation paradigm and signal analysis methodology allowing to disambiguate EEG responses from stimulation artifacts we highlight the spatial extent of the networks associated with clinical effects. Our study includes 26 patients that underwent stereoelectroencephalographic investigations for drug‐resistant epilepsy, having 337 depth electrodes with 4,351 contacts sampling most brain structures. The routine high‐frequency electrical stimulation protocol for eloquent cortex mapping was altered in a subtle way, by alternating the polarity of the biphasic pulses in a train, causing the splitting the spectral lines of the artifactual components, exposing the underlying tissue response. By performing a frequency‐domain analysis of the EEG responses during DES we were able to capture remote activations and highlight the effect''s network. By using standard intersubject averaging and a fine granularity HCP‐MMP parcellation, we were able to create local and distant connectivity maps for 614 stimulations evoking specific clinical effects. The clinical value of such maps is not only for a better understanding of the extent of the effects'' networks guiding the invasive exploration, but also for understanding the spatial patterns of seizure propagation given the timeline of the seizure semiology.     

Immunogenicity Following Administration of BNT162b2 and Ad26.COV2.S COVID-19 Vaccines in the Pregnant Population during the Third Trimester

Globally, COVID-19 vaccines are currently being used to prevent transmission and to reduce morbidity and death associated with SARS-CoV-2 infection. Current research reveals that vaccines such as BNT162b2 and Ad26.COV2.S are highly immunogenic and have high short-term effectiveness for most of the known viral variants. Clinical trials showed satisfying results in the general population, but the reluctance in testing and vaccinating pregnant women left this category with little evidence regarding the safety, efficacy, and immunogenicity following COVID-19 vaccination. With the worldwide incidence of COVID-19 remaining high and the possibility of new transmissible SARS-CoV-2 mutations, data on vaccination effectiveness and antibody dynamics in pregnant patients are critical for determining the need for special care or further booster doses. An observational study was developed to evaluate pregnant women receiving the complete COVID-19 vaccination scheme using the BNT162b2 and Ad26.COV2.S, and determine pregnancy-related outcomes in the mothers and their newborns, as well as determining adverse events after vaccination and immunogenicity of vaccines during four months. There were no abnormal findings in pregnancy and newborn characteristics comparing vaccinated versus unvaccinated pregnant women. COVID-19 seropositive pregnant women had significantly higher spike antibody titers than seronegative patients with similar characteristics, although they were more likely to develop fever and lymphadenopathy following vaccination. The same group of pregnant women showed no statistically significant differences in antibody titers during a 4-month period when compared with case-matched non-pregnant women. The BNT162b2 and Ad26.COV2.S vaccines are safe to administer during the third trimester of pregnancy, while their safety, efficacy, and immunogenicity remain similar to those of the general population.     

Update on the clinical use of kinase inhibitors in melanoma

The identification of targetable molecules in cellular signaling pathways represents a milestone in the treatment of melanoma. Selective inhibitors of these molecules, known as phosphokinases, allow for individual signaling pathways to be “switched off”. This is of particular importance for tumors in which these pathways are constitutively activated by mutations in genes encoding said molecules. Especially patients with BRAF‐mutated melanomas significantly benefit from kinase inhibitor therapies, with the current standard of combined BRAF and MEK inhibition providing very good long‐term disease control. Such regimens have been shown to achieve a progression‐free survival of more than ten months and an overall survival of more than two years, along with good quality of life. Given that the majority of patients develop secondary resistance during long‐term kinase inhibitor therapy, current clinical trials are geared towards finding suitable drug combinations including inhibitors of other signaling pathways as well as immune checkpoint inhibitors. The present review highlights targeted therapies for melanoma currently available as well as potential future options presently under clinical investigation.     

Pancreatico-jejunal vs pancreatico-gastric anastomosis after cephalic duodenopancreatectomy

Pancreatoduodenectomy has been for a long time a procedure with high postoperative morbidity and mortality. Several complications after pancreatic resections are known, but one of the most severe is the fistula of the pancreatic anastomosis. Avoiding the pancreatic fistula caused many surgical innovations regarding the procedure of reestablishing the continuity after pancreatoduodenectomy. The aim of this retrospective study was to compare pancreatico-jejunostomy vs pancreatico-gastrostomy with regard to safety of pancreatic anastomosis after pancreatoduodenectomy. No technique was proved to be superior so far, the benefits of these 2 types of pancreatic anastomosis being the subject for intense debates. From 2000 to 2004, 17 patients underwent pancreatoduodenectomy, for pancreas, ampulla, distal bile duct or duodenum cancers. Pancreatic anastomosis was accomplished by pancreatico-gastrostomy in 11 cases and by pancreatico-jejunostomy in 6 cases. There was no significant difference between the two groups (age, gender and primary disease). Comparison between the two groups was made mainly analysing postoperative mortality and morbidity. Postoperative morbidity was 9,1% after pancreatico-gastrostomy and 33,3% after pancreatico-jejunostomy. Postoperative mortality was none after pancreatico-gastrostomy and 16,7% after pancreatico-jejunostomy. This study seems to demonstrate the superiority of the pancreatico-gastric anastomosis, but in most cases the surgeon will choose based on his experience. These results have to be confirmed or invalidated by a prospective multicentric randomised study.     

HE4 Expression in Plasma Correlates with Surgical Outcome and Overall Survival in Patients with First Ovarian Cancer Relapse

Background

Epithelial ovarian cancer (EOC) remains the main cause of mortality due to gynecological malignancies. Optimal tumor debulking and platinum response are the most important prognostic factors for overall survival (OS) in primary EOC. In the setting of recurrence, the role of cytoreduction is not clear. A critical point is to predict preoperatively the subgroup of patients with optimal surgical outcome. The aim of the study was to analyze the predictive role of HE4 for surgical outcome and platinum response in EOC patients experiencing a first relapse. Secondary aims were the prognostic role of HE4 for OS and progression-free survival (PFS).

Methods

Plasma was obtained before secondary cytoreduction from 73 EOC patients. A total of 66.7 % underwent a total macroscopic tumor clearance; 86.3 % of the patients had disease that responded to platinum therapy. HE4 was detected by enzyme-linked immunosorbent assay. For statistical analysis, the chi-square test, Fisher’s exact test, Kendall’s tau b, and Mann-Whitney U test were used. OS, PFS rates, and respective 95 % confidence intervals (CI) were estimated according to the Kaplan–Meier method.

Results

At a HE4 cutoff value of 250 pMk, a sensitivity of 52 % and a specificity of 93.8 % (p = 0.001, 95 % CI 0.601–0.861) were reached in predicting total macroscopic tumor clearance. Plasma HE4 concentrations together with platinum response were the only independent prognostic factors for OS (p < 0.001, hazard ratio [HR] 18.77, 95 % CI 4.68–75.25; and p = 0.044, HR 3.33, 95 % CI 1.03–10.7, respectively). Together with ascites, HE4 was the only independent predictive factor for surgical outcome (p = 0.029, odds ratio [OR] 7.2, 95 % CI 1.22–42.19 and p = 0.036, OR 10.18, 95 % CI 1.16–88.69, respectively).

Conclusions

HE4 is an independent predictive marker for surgical outcome and OS in patients with recurrent EOC. Larger population studies are needed to validate these results.