ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection

Control of human ascariasis, the most prevalent neglected tropical disease globally affecting 450 million people, mostly relies on mass drug administration of anthelmintics. However, chemotherapy alone is not efficient due to the high re-infection rate for people who live in the endemic area. The development of a vaccine that reduces the intensity of infection and maintains lower morbidity should be the primary target for infection control. Previously, our group demonstrated that immunization with crude Ascaris antigens in mice induced an IgG-mediated protective response with significant worm reduction. Here, we aimed to develop a multipeptide chimera vaccine based on conserved B-cell epitopes predicted from 17 common helminth proteomes using a bioinformatics algorithm. More than 480 B-cell epitopes were identified that are conserved in all 17 helminths. The Ascaris-specific epitopes were selected based on their reactivity to the pooled sera of mice immunized with Ascaris crude antigens or infected three times with A. suum infective eggs. The top 35 peptides with the strongest reactivity to Ascaris immune serum were selected to construct a chimeric antigen connected in sequence based on conformation. This chimera, called ASCVac-1, was produced as a soluble recombinant protein in an Escherichia coli expression system and, formulated with MPLA, was used to immunize mice. Mice immunized with ASCVac-1/MPLA showed around 50% reduced larvae production in the lungs after being challenged with A. suum infective eggs, along with significantly reduced inflammation and lung tissue/function damage. The reduced parasite count and pathology in infected lungs were associated with strong Th2 immune responses characterized by the high titers of antigen-specific IgG and its subclasses (IgG1, IgG2a, and IgG3) in the sera and significantly increased IL-4, IL-5, IL-13 levels in lung tissues. The reduced IL-33 titers and stimulated eosinophils were also observed in lung tissues and may also contribute to the ASCVac-1-induced protection. Taken together, the preclinical trial with ASCVac-1 chimera in a mouse model demonstrated its significant vaccine efficacy associated with strong IgG-based Th2 responses, without IgE induction, thus reducing the risk of an allergic response. All results suggest that the multiepitope-based ASCVac-1 chimera is a promising vaccine candidate against Ascaris sp. infections.

Course and Lethality of SARS-CoV2 Epidemic in Nursing Homes after Vaccination in Florence, Italy

Evidence on the effectiveness of SARS-CoV2 vaccines in nursing home (NHs) residents is limited. We examined the impact of the BNT162b2 mRNA SARS-CoV2 vaccine on the course of the epidemic in NHs in the Florence Health District, Italy, before and after vaccination. Moreover, we assessed survival and hospitalization by vaccination status in SARS-CoV2-positive cases occurring during the post-vaccination period. We calculated the weekly infection rates during the pre-vaccination (1 October–26 December 2020) and post-vaccination period (27 December 2020–31 March 2021). Cox analysis was used to analyze survival by vaccination status. The study involved 3730 residents (mean age 84, 69% female). Weekly infection rates fluctuated during the pre-vaccination period (1.8%–6.5%) and dropped to zero during the post-vaccination period. Nine unvaccinated (UN), 56 partially vaccinated (PV) and 35 fully vaccinated (FV) residents tested SARS-CoV2+ during the post-vaccination period. FV showed significantly lower hospitalization and mortality rates than PV and UV (hospitalization: FV 3%, PV 14%, UV 33%; mortality: FV 6%, PV 18%, UV 56%). The death risk was 84% and 96% lower in PV (HR 0.157, 95%CI 0.049–0.491) and FV (HR 0.037, 95%CI 0.006–0.223) versus UV. SARS-CoV2 vaccination was followed by a marked decline in infection rates and was associated with lower morbidity and mortality among infected NH residents.

Patient doses in endovascular and hybrid revascularization of aortoiliac segment

Objectives: Constantly increasing number of procedures performed – endovascular or hybrid in patients with aortoiliac occlusive disease during the last decades finds its explanation in the lower morbidity and mortality rates, compared to bypass surgery. The purpose of the current survey was to estimate patients’ radiation exposure in aortoiliac segment after endovascular or hybrid revascularization and to study the main factors which have direct contribution. Methods: A retrospective study of 285 procedures conducted with the help of a mobile C-arm system in 223 patients was performed. Procedures were grouped according to criteria such as: type of intervention, vascular access, level of complexity and operating team. Different analyses were performed within the groups and dose values. Results: The median values of kerma–air product (KAP), the number of series and the peak skin dose (PSD) significantly increase with the increasing number of vascular accesses: for one access (16.68 Gy.cm2, 6 and 336 mGy), for two (56.93 Gy.cm2, 11 and 545 mGy), and for three (102.28 Gy.cm2, 15 and 781 mGy). Significant dependence was observed in the case of single access site between the type of access and the dose values: hybrid and retrograde common femoral artery/superficial femoral artery (CFA/SFA) endovascular accesses, 10.06 Gy.cm2/301 mGy and 13.23 Gy.cm2/318 mGy respectively, in contrast with the contralateral CFA and left brachial access, 33 Gy.cm2/421 mGy and 38.33 Gy.cm2/448 mGy respectively. Conclusion: The results demonstrate that the most important factors increasing the dose values are number and type of vascular accesses, followed by the combination and number of implanted stents with the complexity of the procedure. The PSD values for a single procedure were between 2 and 12 times lower than those IAEA proposed as trigger levels for radiation-induced erythema. This study shows that trigger levels were not reached even for patients with repeated procedures in the same segment in 1-year period. Advances in knowledge: The study gives important understanding and clarity on the growing awareness for dose-modifying factors during endovascular and hybrid revascularization of aortoiliac segment.

How Gut Microbiota Supports Immunity, Growth and Development of Preterm Infants: A Narrative Review

ABSTRACTBackground: Gut microbiota, a complex ecosystem consisting of abundant microorganisms, plays a role in preterm infants’ immunity, growth, and development. Dysbiosis or disruption of the gut microbiota can precipitate various diseases, such as allergy or autoimmune disorders in premature infants. Purpose: This study aimed to review gut microbiota in preterm infants and its role in supporting the infants’ immunity, growth, and development. Discussion: Bifidobactericeae is the predominant microbiota in GI tract of preterm infants. However, various factors can influence this gut microbiota e.g., genetics, lifestyle of the mothers (smoking, diet, use of antibiotic, obesity), birth mode, type of feeding, and environmental factors. Gut dysbiosis can result in impaired immune system which predisposes the preterm infants to infections, even fatal adverse event. Furthermore, the growth and development might be affected as well as lead to various neurodevelopmental and psychiatric disorders. Human milk is a prebiotic source which can stimulate the growth of Baifidobactericeae and Bacteroidetes. If the human milk is inadequate or unavailable, the recommended interventions for gut dysbiosis in premature infants are probiotics, prebiotics, or both supplementations (synbiotics). The administration of prebiotics and probiotics associates with lower morbidity and death rates in preterm infants, as well as shorter duration of hospital stay and duration to achieve full enteral feeding. Conclusions: Immunity as well as growth and development of preterm infants are affected greatly by gut microbiota The less diverse microbiota in preterm infants’ gut predispose them to various health problems. Hence, this problem should be managed properly, one of which is prebiotic and probiotic supplementation Keywords: Gastrointestinal Microbiome, Premature, Immunity, Growth, Development

Two-step staged resection of giant olfactory groove meningiomas

Background The surgical treatment of giant olfactory groove meningiomas (OGMs) with marked perilesional brain oedema is still a surgical challenge. After tumour resection, increase of brain oedema may occur causing dramatic neurological deterioration and even death of the patient. The objective of this paper is to describe surgical features of a two-step staged resection of these tumours performed to counter increase of postoperative brain oedema. Methods This two-step staged resection procedure was carried out in a consecutive series of 19 patients harbouring giant OGMs. As first step, a bifrontal craniectomy was performed followed by a right-sided interhemispherical approach. About 80% of the tumour mass was resected leaving behind a shell-shaped tumour remnant. In the second step, carried out after the patients’ recovery from the first surgery and decline of oedema, the remaining part of the tumour was removed completely followed by duro- and cranioplasty. Results Ten patients recovered quickly from first surgery and the second operation was performed after a mean of 12.4 days. In eight patients, the second operation was carried out later between day 25 and 68 due to surgery-related complications, development of a trigeminal zoster, or to a persisting frontal brain oedema. Mean follow-up was 49.3 months and all but one patient had a good outcome regardless of surgery-related complications. Conclusions Our results suggest that a two-step staged resection of giant OGMs minimizes the increase of postoperative brain oedema as far as possible and translates into lower morbidity and mortality.

Update on Robotic Rectal Prolapse Treatment

Rectal prolapse is a condition that can cause significant social impairment and negatively affects quality of life. Surgery is the mainstay of treatment, with the aim of restoring the anatomy and correcting the associated functional disorders. During recent decades, laparoscopic abdominal procedures have emerged as effective tools for the treatment of rectal prolapse, with the advantages of faster recovery, lower morbidity, and shorter length of stay. Robotic surgery represents the latest evolution in the field of minimally invasive surgery, with the benefits of enhanced dexterity in deep narrow fields such as the pelvis, and may potentially overcome the technical limitations of conventional laparoscopy. Robotic surgery for the treatment of rectal prolapse is feasible and safe. It could reduce complication rates and length of hospital stay, as well as shorten the learning curve, when compared to conventional laparoscopy. Further prospectively maintained or randomized data are still required on long-term functional outcomes and recurrence rates.

The role of Doppler ultrasonography in vascular access surveillance—controversies continue

Chronic hemodialysis therapy required regular entry into the patient’s blood stream with adequate flow. The use of arteriovenous fistulas and grafts is linked with lower morbidity and mortality than the use of catheters. However, these types of accesses are frequently affected by stenoses, which decrease the flow and lead to both inadequate dialysis and access thrombosis. The idea of duplex Doppler ultrasound surveillance is based on the presumption that in-time diagnosis of an asymptomatic significant stenosis and its treatment prolongs access patency. Details of performed trials are conflicting, and current guidelines do not support ultrasound surveillance. This review article summarizes the trials performed and focuses on the reasons of conflicting results. We stress the need of precise standardized criteria of significant access stenosis and the weakness of the metaanalyses performed.

Circadian clock precision, health, and longevity

An accurate circadian clock, associated with the precise intrinsic period, tau, can be linked with a definite chronotype and health status. Exemplified by different animal species, and, as we argue herein, may as well be in humans, endogenous tau close enough to 24 hours is associated with higher life expectancy, lower morbidity, and is possibly adhered to moderate morning chronotype. Accurate circadian tau facilitates maintaining a high amplitude of circadian rhythms, a phenotypic trait that is related to health and longevity. Some genetic factors that coordinate tau and ensure circadian clock precision is considered.

786 Retrospective analysis of paediatric ENT surgery outcomes during the COVID pandemic

Introduction Studies show high morbidity/mortality for adults with peri-operative SARS-CoV-2 infection, leading to recommendations curtailing elective operations during the height of the pandemic. Our understanding of the risks associated with paediatric surgery is more limited, with preliminary data suggesting lower morbidity/mortality than in adults. A < 1% incidence of COVID-19 in paediatric patients undergoing preoperative universal screening is reported, and even in those testing positive, morbidity and mortality seem to be low. As waiting lists swell and the detriment associated with delaying surgery mounts, it is imperative to accurately quantify the risks of surgery in the paediatric population. Method Retrospective review of all paediatric ENT operations performed at the Evelina Children’s Hospital at the height of lockdown, from March to May 2020. Results 61 procedures were performed on 56 patients. 50% had a pre-operative SARS-CoV-2 nasopharyngeal swabs. All cases involved a change in anesthetic practice; 2 cases involved a change in surgical practice. We noted 2 medical complications and 1 surgical complication. All patients are currently extant. No staff or patients subsequently developed COVID. Conclusions Our perioperative infection rates and mortality/morbidity figures concord with figures published elsewhere in literature. We are cautiously optimistic regarding risks associated with paediatric ENT surgery.