As the SARS-CoV-2 pandemic continues to rage worldwide, the emergence of numerous variants of concern (VOC) represents a challenge for the vaccinal protective efficacy and the reliability of ...commercially available high-throughput immunoassays. Our study demonstrates the administration of two doses of the BNT162b2 vaccine that elicited a robust SARS-CoV-2-specific immune response which was assessed up to 3 months after full vaccination in a cohort of 37 health care workers (HCWs). SARS-CoV-2-specific antibody response, evaluated by four commercially available chemiluminescence immunoassays (CLIA), was qualitatively consistent with the results provided by the gold-standard in vitro neutralization assay (NTA). However, we could not observe a correlation between the quantity of the antibody detected by CLIA assays and their neutralizing activity tested by NTA. Almost all subjects developed a SARS-CoV-2-specific T-cell response. Moreover, vaccinated HCWs developed a similar protective neutralizing antibodies response against the EU (B.1), Alpha (B.1.1.7), Gamma (P.1), and Eta (B.1.525) SARS-CoV-2 variants, while Beta (B.1.351) and Delta (B.1.617.2) strains displayed a consistent partial immune evasion. These results underline the importance of a solid vaccine-elicited immune response and a robust antibody titre. We believe that these relevant results should be taken into consideration in the definition of future vaccinal strategies.
Coronary catheterization after transcatheter aortic valve implantation (TAVR) may be challenging. The main objective of the study is to assess the feasibility of coronary catheterization and ...angioplasty according to each type of valve.
We retrospectively studied coronary angiography or percutaneous angioplasty procedures after TAVR in two different centers. The catheterization success of coronary artery was evaluated according to the quality of engagement in ostium and opacification of the artery. Other indicators were collected including catheters used, fluoroscopy and angiography times, DAP and the volume of the contrast agent.
Among 1512 TAVR procedures, 33 patients were included. The Sapien 3® valve was implanted in 22 patients and the Evolut® in 11 patients (7 Evolut-R® and 4 Evolut Pro®). Coronary angiography with selective or partially selective catheterization has been successfully performed in all patients with a Sapien 3® valve. In the Evolut® group we identified 3 cases of non-selective catheterization for the right coronary and 1 case for the left coronary. Standard Judkins catheters seem to be the most suitable for both types of valve with very good efficiency.
The results of our study is promising for the future of TAVR with a coronary catheterization success rate close to 100% with some difficulties for the Evolut® supra-annular valves. Special attention should be paid to the technique of implantation and orientation of cups in the aortic sinus.
mild head trauma (MHT) is defined as a transient neurological deficit after trauma with a history of impairment or loss of consciousness lasting less than 15 min and/or posttraumatic amnesia, and a ...Glasgow Coma Scale between 13 and 15 on hospital admission. We evaluated 50 MHT patients 18 months after the trauma, addressing signs and symptoms of post-concussion syndrome, quality of life and the presence of anxiety and depression. We correlate those findings with the S100B protein levels and cranial CT scan performed at hospital admission after the trauma.
patients were asked to fill out questionnaires to assess quality of life (SF36), anxiety and depression (HADS), and signs and symptoms of post-concussion syndrome. For the control group, we asked the patient's household members, who had no history of head trauma of any type, to answer the same questionnaires for comparison.
total quality of life index for patients with MHT was 58.16 (+/-5), lower than the 73.47 (+/-4) presented by the control group. Twenty patients (55.2%) and four (11.1%) controls were depressed. Seventeen patients (47.2%) presented anxiety, whereas only eight (22.2%) controls were considered anxious. Victims of MHT complained more frequently of loss of balance, dry mouth, pain in the arms, loss of memory and dizziness than their respective controls (p<0.05). We found no correlation between the presence of these signs and symptoms, quality of life, presence of anxiety and depression with S100B protein levels or with presence of injury in the cranial CT performed at hospital admission.
MHT is associated with a higher incidence of post-concussion syndrome symptoms, lower quality of life and anxiety than their respective controls even 18 months after the trauma.
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder, characterized by exocrine pancreatic insufficiency, skeletal abnormalities and bone marrow (BM) dysfunction with an increased risk ...to develop myelodysplastic syndrome and/or acute myeloid leukaemia (MDS/AML). SDS is caused, in nearly 90% of cases, by two common mutations (that is, c.183_184TA>CT and c.258+2T>C) in exon 2 of the SBDS gene, localized on chromosome 7. Clonal chromosome anomalies are often found in the BM of SDS patients; the most frequent is an isochromosome for long arms of chromosome 7, i(7)(q10). We studied eight patients with SDS carrying the i(7)(q10) who were compound heterozygotes for SBDS mutations. By assessing the parental origin of the i(7)(q10) using microsatellite analysis, we inferred from the results which mutation was present in double dose in the isochromosome. We demonstrate that in all cases the i(7)(q10) carries a double dose of the c.258+2T>C, and we suggest that, as the c.258+2T>C mutation still allows the production of some amount of normal protein, this may contribute to the low incidence of MDS/AML in this subset of SDS patients.
A NOD/Scid mouse expressing enhanced green fluorescent protein (eGFP) is described, in which human and mouse tumors marked with red fluorescent protein can be established in vivo, both at ...subcutaneous and orthotopic locations. Using light microscopy as well as multiphoton confocal microscopy techniques, we visualized in detail the intricate colocalization of tumor and host cells in situ. Moreover, using fluorescence-activated cell sorting (FACS), we were able to completely separate the host cells from the tumor cells, thus providing a system for detailed cellular and molecular analysis of tumor-host cell interactions. The fact that tumor and host cells can be reliably identified also allowed us to detect double-positive cells, possibly arising from cell fusion events or horizontal gene transfer. Similarly, the model can be applied for the detection of circulating metastatic cells and for detailed studies on the vascular compartments within tumors, including vasculogenic mimicry. Thus, the model described should provide significant insight into how tumor cells communicate with their microenvironment.--Niclou, S. P., Danzeisen, C., Eikesdal, H. P., Wiig, H., Brons, N. H. C., Poli, A. M. F., Svendsen, A., Torsvik, A., Enger, P. Ø., Terzis, J. A., Bjerkvig, R. A novel eGFP-expressing immunodeficient mouse model to study tumor-host interactions.
Vascular complications are frequent in the context of transcatheter aortic valve replacement and may require the implantation of a covered stent graft in the common femforal artery. However, common ...femoral artery is considered to be at high risk of stent fracture or occlusion due to high mobility of the hip joint.
We analyzed medical records of patients with transcatheter aortic valve replacement related vascular complications between 2015 and 2018, treated with commom femoral artery transluminal angioplasty or surgery. Vascular complications or suspect symptoms were followed up by phone calls.
Among 552 patients, 43 patients were included. Twelve (11.6 %) were managed by prolonged balloon inflation, 5 (11.6 %) by first line surgery and 26 (60.4 %) by the implantation of a covered stent graft. Among the latter group, the covered stent graft was efficient in 24 patients (92.3 %). The median follow-up was 430 days 3-1499. The first-line surgery group had a higher risk of red blood cell transfusion and all causes mortality. At follow-up, no patient had suspicious symptoms of vascular covered stent complication. Four patients (9.3 %) had US-doppler or CT vascular imaging at follow-up, showing no evidence of stent fracture or occlusion.
In our study, the implantation of a covered stent graft in the common femoral artery was an efficient and safe strategy for the management of transcatheter aortic valve replacement related vascular complications.
We created an experimental model of urethral defect and then repaired it using a tunica vaginalis graft applied on the dorsal surface of the urethra. We studied the histological and radiological ...characteristics of free tunica vaginalis graft urethroplasty.
In 20 New Zealand rabbits a dorsal urethral defect was created by excising a portion of the dorsal urethral surface. The tunica vaginalis graft was placed dorsally over the corpora cavernosa and tied with 4 interrupted sutures. The mucosal margin of the urethral defect was sutured to the graft using 6–zero polydioxanone sutures in continuous fashion. The animals were divided into 4 equal groups and were sacrificed 14 days, and 4, 8 and 12 weeks after surgery, respectively. A retrograde urethrogram was done at autopsy. The penis was sent for histological analysis and an experienced pathologist evaluated the severity of acute and chronic inflammation, foreign body reaction and scar formation.
There were no deaths related to the procedure and no intraoperative complications. All rabbits voided spontaneously after surgery. Retrograde urethrograms showed no fistula or stricture. As time after surgery increased, the signs of inflammation response disappeared, and the orientation of collagen fibrils and smooth muscle fascicles resembled that of a normal urethra. The mesothelial lining of the tunica vaginalis gradually became replaced by a more stratified epithelial lining, similar to the urothelial lining of the native urethra.
In the current study we noted that a tunica vaginalis graft placed dorsally can be a successful urethral substitute in the animal model.
Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical ...outcomes and prevent adverse left ventricular remodeling.
In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume.
A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval CI, 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups.
In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).
Small volume hypertonic resuscitation is a relatively new conceptual approach to shock therapy. It was originally based on the idea that a relatively large blood volume expansion could be obtained by ...administering a relatively small volume of fluid, taking advantage of osmosis. It was soon realized that the physiological vasodilator property of hypertonicity was a useful byproduct of small volume resuscitation in that it induced reperfusion of previously ischemic territories, even though such an effect encroached upon the malefic effects of the ischemia-reperfusion process. Subsequent research disclosed a number of previously unsuspected properties of hypertonic resuscitation, amongst them the correction of endothelial and red cell edema with significant consequences in terms of capillary blood flow. A whole set of actions of hypertonicity upon the immune system are being gradually uncovered, but the full implication of these observations with regard to the clinical scenario are still under study. Small volume resuscitation for shock is in current clinical use in some parts of the world, in spite of objections raised concerning its safety under conditions of uncontrolled bleeding. These objections stem mainly from experimental studies, but there are few signs that they may be of real clinical significance. This review attempts to cover the earlier and the more recent developments in this field.
O uso de soluções hipertônicas para reanimação de pacientes em choque é um conceito relativamente novo. Baseou-se originalmente na idéia de que uma expansão volêmica significativa podia ser obtida às custas de um volume relativamente diminuto de infusão, aproveitando a propriedade física de osmose. Logo ficou claro que a capacidade fisiológica de produzir vasodilatação, compartilhada por todas as soluções hipertônicas, seria valiosa para reperfundir territórios tornados isquêmicos pelo choque, embora os malefícios da seqüência isquemia – reperfusão devessem ser considerados. Pesquisa subseqüente revelou propriedades antes insuspeitadas da reanimação hipertônica. Verificou-se que este procedimento revertia instantaneamente o edema endotelial e de hemácias, com importantes conseqüências em termos de circulação capilar. Mais recentemente, um conjunto de efeitos da hipertonicidade sobre o sistema imune vem sendo estudado, mas as possíveis implicações destas descobertas em relação ao cenário clínico ainda suscitam discussão. As soluções hipertônicas estão em uso em algumas partes do mundo, apesar de objeções levantadas contra tal uso, em virtude de dados experimentais derivados de experimentos de hemorragia não controlada. Tais objeções não parecem se justificar em face dos resultados obtidos numa série de ensaios clínicos e no uso corrente destas soluções. Esta revisão procura cobrir um pouco da história, remota e recente, deste campo do conhecimento.
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