Infection Research Articles

Effectiveness of COVID-19 vaccines administered in the 2023 autumnal campaigns in Europe: Results from the VEBIS primary care test-negative design study, September 2023–January 2024

In autumn 2023, European vaccination campaigns predominantly administered XBB.1.5 vaccine. In a European multicentre study, we estimated 2023 COVID-19 vaccine effectiveness (VE) against laboratory-confirmed symptomatic infection at primary care level between September 2023 and January 2024. Using a test-negative case–control design, we estimated VE in the target group for COVID-19 vaccination overall and by time since vaccination. We included 1057 cases and 4397 controls. Vaccine effectiveness was 40 % (95 % CI: 26–53 %) overall, 48 % (95 % CI: 31–61 %) among those vaccinated < 6 weeks of onset and 29 % (95 % CI: 3–49 %) at 6–14 weeks. Our results suggest that COVID-19 vaccines administered to target groups during the autumn 2023 campaigns showed clinically significant effectiveness against laboratory-confirmed, medically attended symptomatic SARS-CoV-2 infection in the 3 months following vaccination. A longer study period will allow for further variant-specific COVID-19 VE estimates, better understanding decline in VE and informing booster administration policies.

PRIMARY REPAIR OF PROXIMAL (GRADE IV) HYPOSPADIAS UTILIZING TUNICA VAGINALIS VASCULARISED FLAP

Background: Proximal (grade IV) hypospadias like scrotal and perineal are considered as severe challenging types for surgeons, problematic for the patients and their families, More than three hundreds surgical techniques were used to manage different type of hypospadias . Most of them associated with high incidence of complications. These complications are much more common in the proximal types as in our study. Post-operative fistula formation is expected complications. Utilising the tunica vaginalis as an additional layer during repair may prevent such complications. In this study we evaluated the benefits of using the tunica vaginalis flap as a supportive layer in the primary repair. Most related literatures about this subject used this technique after surgery to manage cases with post-operative fistulas. In the contrary we used this technique during the formal surgery to cover the new urethra to prevent fistula formation not after surgery. Aims of the study: A retrospective study, on fourteen patients with severe hypospadias (Proximal types), to evaluate the role of tunica vaginalis flap in the primary repair of the hypospadias. Patients and Methods: Between January 2016 and January 2024, fourteen children with Grade IV hypospadias were operated on. Only severe cases were treated with this method other simpler and more common cases were treated by different surgeries like Snodgrass technique. The age range was 2 to 16 years. All of them had 2 staged repair the first stage was correcting the chordae by incising the urethral plate excising the fibrous chordae tissues then covering the bare shaft with dorsal flaps. The tunica flap was used in the second stage which was done 6 to 12 months later. Folly's catheter was used for ten to fourteen days after surgery. And the patients were followed for a variable time 3months to 2 years period for the development of complications like fistula formation or stricture. Cosmetic considerations were also noted. Results: All the fourteen patients had proximal types (Grade IV) hypospadias. After surgery all patients had a good cosmetic outcome no fistula formation two had mild distal urethral stricture cured after few urethral dilatation. No post-operative penile torsion was noted. Two patients developed local infection treated conservatively. One patient had partial glanular dehiscence at the distal end which had no clinical significance. One patient complained from on and off penile cutaneous swelling lasted 3 weeks. Conclusions: Using tunica vaginalis vascularised flap to cover the new urethra in severe proximal hypospadias during the second stage seems to be a successful way in preventing fistula formation without increasing the patient's morbidity.

Geographic heterogeneity of SARS-CoV-2 circulation in Abidjan, Ivory Coast: a prospective study.

Few studies on SARS-CoV-2 seroprevalence in Ivory Coast have been conducted since the first case was reported on March 11, 2020. The main objective of this study was to observe and better understand the circulation of SARS-CoV-2 in Abidjan. This prospective study collected data concerning age, sex, vaccination status, municipality of origin, monthly income, frequency of malaria, and frequency of diarrheal diseases in persons who gave their informed consent. Venous blood samples were taken to test for anti-SARS-COV-2 antibodies (IgM and IgG) using the VIDAS automated system. A total of 1504 patients were recruited and tested for antibodies directed against SARS-COV-2. Data analysis revealed the presence of anti-SARS-CoV-2 in 53.5% of participants, 17.3% of the participants had a previous symptomatic infection, 31.4% had an asymptomatic infection, and 44.8% were never in contact with the virus. Seroprevalence of SARS-CoV-2 was higher in Marcory (70.9%) and Cocody (61.1%) than in the remaining townships (48.4%). Township rates of serologically confirmed SARS-CoV-2 infection correlated with poverty index (p = 0.025), children < 5 years' proportion in the township (p = 0.026), and levels of malaria (p = 0.034). In the city of Abidjan, COVID-19 is strongly modulated by poverty, the proportion of babies and toddlers in the community, or exposure to malaria.

Primary exposure to Zika virus is linked with increased risk of symptomatic dengue virus infection with serotypes 2, 3, and 4, but not 1.

Infection with any of the four dengue virus serotypes (DENV1-4) can protect against or enhance subsequent dengue depending on preexisting antibodies and infecting serotype. Additionally, primary infection with the related flavivirus Zika virus (ZIKV) is associated with increased risk of DENV2 disease. Here, we measured how prior DENV and ZIKV immunity influenced risk of disease caused by DENV1-4 in a pediatric Nicaraguan cohort. Of 3412 participants in 2022, 10.6% experienced dengue cases caused by DENV1 (n = 139), DENV4 (n = 133), DENV3 (n = 54), DENV2 (n = 9), or an undetermined serotype (n = 39). Longitudinal clinical and serological data were used to define infection histories, and generalized linear and additive models adjusted for age, sex, time since last infection, and year, and repeat measurements were used to predict disease risk. Compared with flavivirus-naïve participants, primary ZIKV infection was associated with increased risk of disease caused by DENV4 (relative risk = 2.62, 95% confidence interval: 1.48 to 4.63) and DENV3 (2.90, 1.34 to 6.27), but not DENV1 infection. Primary DENV infection or DENV followed by ZIKV infection was also associated with increased risk of DENV4 disease. We reanalyzed 19 years of cohort data and demonstrated that prior flavivirus immunity and antibody titer had distinct associations with disease risk depending on incoming serotype. We thus find that prior ZIKV infection, like prior DENV infection, is associated with increased risk of disease with certain DENV serotypes. Cross-reactivity among flaviviruses should be considered when assessing vaccine safety and efficacy.

Auditory brainstem implants: an analysis of adverse events in the MAUDE database

ObjectiveAuditory Brainstem Implants (ABI) are used to restore hearing in patients lacking appropriate cochlear anatomy and/or cochlear nerve. The objective of this study was to examine the Manufacture and User Facility Device Experience (MAUDE) database to analyze adverse events. Study designThis is a study of a multi-institutional database maintained by the US FDA. SettingA database analysis was performed via collaboration of multiple clinicians at tertiary referral centers. MethodsThe MAUDE database was queried for Medical Device Reports (MDRs) relating to ABIs. MDRs were identified using the advanced search term “Implant, Auditory Brainstem” and reviewing all reports with the basic search term “Brainstem Implant”. All collected reports were individually reviewed. ResultsA total of 265 individual patient reports were reviewed, of which 55 reports met inclusion criteria. Reports regarding audiologic outcome included failure to provide hearing benefit (n = 27), implant failure/device malfunction (n = 10), and device non-use (n = 6). Postoperative complications included local skin infection (n = 3), CSF leak (n = 3), elevated ICP (n = 1), surgical site dehiscence (n = 1), swelling (n = 1), seroma formation requiring drainage (n = 1), and meningitis (n = 2). Two patients had dislodged magnets during 1.5 Tesla MRI acquisition. There were 35 instances of full explantation of the device and 1 partial removal; 13 patients had a new device implanted following explantation. ConclusionsPoor hearing results, device failure, and non-use were commonly reported causes for explanation in this analysis. This information can aid physicians in counseling patients and family members and managing device expectations.

Finite element analysis of reconstruction plates in mandibular defects

Segmental defects in the mandibular bone can occur after local trauma, infection, or surgical resection. Several reconstructive possibilities are currently available, and temporary stabilization of bone segments with reconstruction plates is commonly used when immediate bone reconstruction is not possible. However, little attention has been paid to the biomechanical aspects involved in this approach, and studies conducted with biomodels face the difficulty of simulating the muscular forces involved. The use of Finite Element Analysis allows for the mathematical evaluation of structures in a controlled environment, applying forces at any point and/or direction, assessing material deformation, as well as the tension applied to them. Thus, the aim of this study was to evaluate reconstruction plates used on segmental defects through mathematical analysis using finite elements. After simulation, lower stress values were found on thicker plates, suggesting greater resistance to fracture. Conversely, significantly increased stress values on the screws were present in thicker plates.

Does raising awareness about inequality decrease support for school closures? An information treatment survey experiment during the COVID-19 pandemic

The increase in inequalities during the ongoing COVID-19 pandemic has been the topic of intense scholarly and public debate. School closures are one of the containment measures that have been debated most critically in this regard. What drives support for closures of schools and pre-school services (daycare/kindergarten) during a public health crisis such as the current COVID-19 pandemic? More specifically, does inequality awareness affect this support? Theoretically, we assume that providing information on current levels of inequality can change policy preferences, as it increases awareness of their consequences for inequality. Moreover, we assume that the strength of the association between information provision and policy support varies across individuals—depending on their exposure to these policies, and the political attitudes that they hold. To identify causal linkages between awareness of inequalities and support for school and daycare/kindergarten closures, we use a survey experiment with information treatment, in which we randomly assign information designed to prime the respondents to think about either education inequality, gender inequality, or both. The experiment, involving more than 3,000 respondents, was conducted in the spring of 2021 at the end of a prolonged lockdown in Germany when a new piece of legislation was enacted, enabling or restricting school reopenings based on local infection rates. Using Probit Regression models for dichotomous dependent variables, we show that raising awareness of education inequality and gender inequality via an information treatment is associated with decreasing support for preschool and primary school closures. We also find that past exposure to school-closure policies strengthens the effects of information treatments, whereas previous political attitudes do not moderate the association between information treatments and support for preschool and school closures.

Early vs. late lead extraction in CIED infections: evaluating the interplay of infection type, timing, and comorbidities

Abstract Background Cardiovascular Implantable Electronic Devices (CIEDs) may be associated with peri- and post-procedural complications like device-related infection, one of the most serious challenge of CIEDs therapy associated with significant morbidity, mortality, and financial healthcare burden. Despite a routine use of antibiotics, recent studies reported an increase in CIEDs infections, with or without systemic involvement, that often require surgical interventions like transvenous lead extraction. Purpose This study evaluates the outcomes of transvenous lead extraction in patients with infected CIEDs, focusing on the impact of early versus delayed extraction timing on patient outcomes. Methods A retrospective analysis of 165 patients who underwent transvenous lead extraction for CIED infections between 2019 and 2022 was conducted. Patients were categorized into systemic (n=64) or local (n=101) infection groups and further into early (within 7 days from admission, n=102) or delayed (after 7 days, n=63) extraction groups. Post-procedural outcomes, including septic shock, complications, and mortality rates were described. Results The majority of patients were male (75%) with a median age of 73 (IQR 64-80) years. In the early extraction group, the 1-year mortality rate was significantly lower at 6.4%, compared to 25% in the delayed group. Patients with systemic infections had higher 1-month and 1-year mortality rates compared to those with local infections. The success rates of complete device removal were similar across groups. However, the delayed extraction group exhibited higher rates of comorbidities like anemia, chronic kidney disease, and elevated C-reactive protein levels, which were prevalent in 70% of these patients, compared to 45% in the early extraction group. Conclusions Timely management of CIED infections is crucial for improving patient outcomes. Early extraction within 7 days from hospital admission is associated with significantly lower mortality, regardless of local or systemic infection. Patients undergoing delayed extraction often present with greater comorbidity, which may contribute to their higher mortality rates. This underscores the importance of considering patient comorbidities and prompt intervention in managing CIED infections.

No lead left behind: procedural outcome of excimer laser powered extractions in patients with abandoned leads - a GALLERY subgroup analysis

Abstract Background Lead dwell time &amp;gt; 10 years, has been recognized as a predictive factor for procedural failure of transvenous lead extraction (TLE). However, there is a limited information concerning the specific outcomes of TLE for abandoned leads when employing the excimer laser-powered sheath. Objective The purpose of this study was to investigate the procedural outcomes of individuals with abandoned leads undergoing TLE with excimer laser-powered sheath as first tool strategy. Methods A subgroup analysis of patients with abandoned leads of the GALLERY (GermAn Laser Lead Extraction RegistrY) database was conducted. Patients were categorized into two groups based on the presence of abandoned leads at the time of extraction: Group 1 for those with abandoned leads, and Group 2 for those without abandoned leads. Results Among the 2524 patients, 749 individuals (29.7%) had abandoned leads (Group 1) at the time of the procedure. Patients in Group 1 were typically older (69.1±13 vs. 67.6±14.1 years; p=0.026) and 23.5% were female. Leading extraction indication was local infection (37.4% vs. 34.3%, p=0.145), systemic infection (33.2% vs. 26.6%, p=0.001) and lead dysfunction (24.3% vs. 33.5%, p&amp;lt;0.001). Additionally, more patients in Group 1 presented with cardiac resynchronization therapy (CRT) devices (30.4% vs. 22.9%, p&amp;lt;0.001). Significant differences were observed in the mean number of total leads (3.4±1.1 vs. 2.0±0.7, p&amp;lt;0.001), median age of the oldest lead (117 vs. 87 months; p&amp;lt;0.001), and the number of right-sided leads (41.7% vs. 29.5%, p&amp;lt;0.001), all of which were higher in Group 1. Median hospital stay (10 vs. 9 days; p=0.002), median procedural time (105 vs. 75 minutes; p&amp;lt;0.001) and use of additional tools (11.2% vs. 4.7%, p&amp;lt;0.001) were significantly higher in Group 1. There was no difference regarding clinical success (p=0.32) between the groups. However, complete procedural success was significantly higher in Group 2 (84.9% vs. 94.2%, p&amp;lt;0.001). All-cause mortality did not differ between the groups (p=0.111) but procedural-related mortality was higher in Group 1 (2.9% vs. 0.6%, p&amp;lt;0.001). The overall complications rate was also significantly higher in Group 1 (5.7% vs. 3.7%, p=0.03). Conclusion Patients with abandoned leads presented an increased procedural complexity, less procedural and clinical success despite the use of multiple tools, longer hospital-stay and higher procedure-related mortality rates. Therefore, an extraction strategy should be considered before deciding to abandon non-functional or dysfunctional leads.

Primary vs. secondary wound closure following transvenous system explantation in CIED infection

Abstract Background &amp; Introduction Patients undergoing an explantation of cardiac implantable electronic devices (CIED) receive either a primary or secondary wound closure or open wound treatment depending on departmental practice. To date, there is limited data on whether secondary wound closure or open wound treatment has any benefit in terms of future complications although it requires a more intensive wound care. Material &amp; Methods Patients who underwent CIED explantation for system infection at our institution between 2016 and 2022 were retrospectively reviewed. From this cohort, patients diagnosed with pocket infection were isolated and divided into two groups: (i) Patients who underwent primary wound closure with or without temporary use of a drain (PG), and (ii) patients who underwent secondary wound closure or open wound management (SG). Patients were followed up by telephone contact for short and long term complications. Results 387 patients underwent CIED explantation due to local or system infection at a heart centre. Of this cohort, 205 patients (135 female; 74.4 ±11.4 y.o.) had a pocket infection. In addition to local infection, 25.9% of all patients presented with a pocket perforation. The onset of infection was early (within 28 days) in 16.1%, intermediate (29 days - 1 year) in 50.2% and late (after 1 year) in 33.2%. Wound swabs and blood cultures were positive for pathogens in 61.0% and 14.1% respectively. 136 (65.9%) underwent primary wound closure, 69 (34.1%) underwent secondary wound closure or open wound management. Post-operative (p.o.) hematoma was present in 12.2% of the cases (6.6% of PG and 24.6% of SG). The risk of developing a p.o. hematoma was significantly more likely in the SG (OR=4.61; IC95%: 1.93 − 11.01). Re-implantation occurred in 70.2%, including 25.7% of leadless pacemakers an 1.5% subcutaneous defibrillators. In 13.7% re-implantation was not indicated, 4.4% refused and 1.0% had contraindications. Mean length of hospitalization was 12.4 ±8.9 days in the PG and 15.7 ±9.6 days in the SG (ρ = 0.0083). A total of 24 (34.8%) patients were discharged with an open wound with or without vacuum treatment (0.74% of PG; 34.8% of SG). Mean telephonic follow-up was 27 ±18 months in 147 cases (n1 = 99; n2 = 48). 91.8% of the cases had no pathological findings at follow-up. 2.7% developed a wound healing disorder (WHD) which was treated conservatively, 4.1% required revision, 0.7% explantation and 0.7% endocarditis. No statistical difference of complication risk between both groups was found (OR=1.8; IC95%: 0.51 - 6.17). Summary &amp; Conclusions Management of CIED pocket infection with primary wound closure compared to secondary wound closure showed a statistically significant shorter hospital stay and reduced likelihood of post-operative hematoma, with no increase in long-term complication rates.

Procedural outcome of transvenous lead extraction in patients with right-sided leads - a GALLERY subgroup analysis

Abstract Background Transvenous lead extraction (TLE) in patients with cardiac implantable electronic devices has become a well-established therapy for patients with lead complications. However, there is limited information on specific outcomes for patients with right-sided leads compared to patients with left-sided leads undergoing TLE. Aim The aim of this study was to analyze patient characteristics, procedural outcomes as well as adverse events and mortality of patients with right-sided leads undergoing TLE with the excimer laser sheath as a first line therapy. Methods We performed a subgroup analysis of all reported patients in the GALLERY (GermAn Laser Lead Extraction RegistrY) with unilateral right-sided leads (Group 1) or unilateral left-sided leads (Group 2). Results 2438 patients with unilateral leads were analyzed. 750 patients were in Group 1 and 1688 patients were in Group 2. Patients in Group 1 were older (71.1 ± 13.9 vs. 66.5 ± 13.6; p &amp;lt; 0.001), more patients were female (31.7% vs. 22.1%, p &amp;lt; 0.001), had a lower body-mass-index (26.8 ± 4.5 vs. 27.2 ± 4.7; p=0.03) and more patients were pacemaker dependent (44.9% vs. 25.4%, p&amp;lt; 0.001). The primary indication for TLE was local infection (46.0% vs. 30.6%, p&amp;lt; 0.001) in Group 1 and lead dysfunction (20.0% vs. 36.1%, p&amp;lt; 0.0001) in Group 2. The frequency of TLE for systemic infection was indifferent between groups (28.9% vs. 27.6%, p=0.532). The most common device to be extracted were pacemakers (80.1% vs. 22.7%, p&amp;lt; 0.001) in Group 1 and implantable cardioverter-defibrillators (ICD) (9.7 vs. 45.3%, p&amp;lt; 0.001) and cardiac resynchronization therapy devices (CRT) (9.6 vs. 31.5%); p&amp;lt; 0.001) in Group 2. The mean number of total leads was not different between groups (2.4 ± 0.9 for Group 1 vs. 2.3 ± 1.0 for Group 2; p=0.98), however median lead dwell time (120 vs. 85 months, p&amp;lt; 0.001), patients with abandoned leads (32.0% vs. 25.9%; p=0.0022) and the use of additional extraction tools (8.4% vs. 5.7%, p=0.016) were significantly higher in Group 1. Patients with right-sided leads had a longer median hospital stay (10 vs. 9 [5; 15] p=0.001). Complete procedural success was higher in patients Group 2 (89.1 vs. 93.1%, p=0.001) but there was no difference in clinical success rates (97.7% vs. 98.0%, p=0.74). There was no difference in overall complication rates (4.3% vs. 4.2%, p=0.945). Neither procedure related mortality (0.3% vs. 0.7%, p=0.2940) nor all-cause mortality (3.5% vs. 3.4%, p=0.9101) differed between groups. Conclusion TLE procedures in patients with right-sided leads showed a lower procedural success rate and a higher need of additional tools. This patient group was older, more often pacemaker dependent and had a higher number of abandoned leads. Despite different patient and lead characteristics, there were no differences in clinical success-rates, procedure related complications or all-cause mortality between groups.

COVID-19 and male fertility: short- and long-term impacts of asymptomatic vs. symptomatic infection on male reproductive potential

BackgroundStudies exploring the effect of COVID-19 on male reproductive system suggest a detrimental association, however with conflicting results. The aim of this study was to assess the association between COVID-19 infection and male reproductive potential including hormone profiles and semen parameters.MethodsThis prospective cohort study included 48 patients with confirmed COVID-19 infection. Patients were subdivided into an asymptomatic group (n = 30) and a group with COVID-19 symptoms (n = 18). Serum hormone levels including testosterone, LH, FSH and estradiol were collected during active infection (baseline, time 0), and at 3 and 6 months following COVID-19 infection. Semen samples (basic semen analysis and oxidation reduction potential) were examined at 3 and 6 months following infection. Student and paired-t tests were used to compare continuous variables between the study groups and across the studied time intervals, respectively. Multivariate binary logistic regression analysis was performed to explore predictors for COVID-19 symptoms during active infection.ResultsPatients with COVID-19 symptoms were significantly older (p = 0.02) and had significantly lower serum testosterone levels (p = 0.01) and significantly higher LH: testosterone ratio (p = 0.01) than asymptomatic patients. Multivariate analysis revealed older age (OR = 1.18, p = 0.03) and lower serum testosterone level (OR = 0.8, p = 0.03) as independent predictors of symptomatic COVID-19 infection. Significant increase in testosterone (p &amp;lt; 0.001 for both) and decrease in LH (p = 0.02, p = 0.007) and LH: testosterone (p = 0.02, p = 0.005) levels were observed at 3 and 6 months in patients with COVID-19 symptoms. Asymptomatic patients demonstrated significant increase in testosterone (p = 0.02) and decrease in LH: testosterone (p = 0.04) levels only at 3 months following COVID-19 infection. No significant differences were observed between the two study groups with regards to the semen analysis results obtained at 3 or 6 months following COVID-19 infection.ConclusionSignificantly lower testosterone values are associated with worse disease severity among men with COVID-19 infection. This association appears to be temporary as a significant increase in testosterone levels are witnessed as early as 3 months following recovery. No significant detrimental effect for COVID-19 infection on testicular sperm production is found in this patient population.

End-organ damage from neonatal invasive fungal infection: a 14-year retrospective study from a tertiary center in China

BackgroundInvasive fungal infection (IFI) has become an increasing problem in NICU neonates, and end-organ damage (EOD) from IFI is one of the leading causes of morbidity and mortality in neonates. This study was conducted to summarize clinical data on epidemiology, risk factors, causative pathogens, and clinical outcomes of IFI-associated EOD among neonates in a center in China for the sake of providing references for prevention and treatment of fungal infections in neonates in future.MethodsThe clinical data of IFI neonates who received treatment in a tertiary NICU of China from January 2009 to December 2022 were retrospectively analyzed, including causative pathogens and the incidence of EOD. The neonates were divided into EOD group and non-EOD (NEOD) group. The general characteristics, risk factors and clinical outcomes of the two groups were compared.ResultsIncluded in this study were 223 IFI neonates (137 male and 86 female) with a median gestational age (GA) of 30.71 (29,35) weeks and a median birth weight (BW) of 1470 (1120,2150) g. Of them, 79.4% were preterm infants and 50.2% were born at a GA of ≥ 28, <32 weeks, and 37.7% with BW of 1000–1499 g. Candida albicans (C. albicans) was the most common Candida spp. in these neonates, accounting for 41.3% of all cases, followed by C. parapsilosis (30.5%) and C. glabrata (7.2%). EOD occurred in 40 (17.9%) of the 223 cases. Fungal meningitis was the most common EOD, accounting for 13.5% of the 40 EOD cases. There was no significant difference in the premature birth rate, delivery mode, GA and BW between EOD and NEOD groups, but the proportion of male infants with EOD was higher than that without. There was no significant difference in antenatal corticosteroid use, endotracheal intubation, invasive procedures, use of antibiotics, total parenteral nutrition, blood transfusion, postnatal corticosteroid use, fungal prophylaxis and the incidence of necrotizing enterocolitis between the two groups, but the proportion of C. albicans infection cases in EOD group was higher than that in NEOD group (57.5% vs. 37.7%). Compared with NEOD group, the proportion of cured or improved infants in EOD group was significantly lower (P < 0.05), and the number of infants who died or withdrew from treatment was larger (P < 0.05).ConclusionsOur retrospective study showed that preterm infants were prone to fungal infection, especially very preterm infants. C. albicans was the most common Candida spp. for IFI, and was a high-risk factor for EOD. EOD can occur in both full-term and premature infants, so the possibility of EOD should be considered in all infants with IFI.

Inhibition of Integrin VLA-3 and Tetraspanin CD151 Protects Against Neutrophil-Mediated Endothelial Damage.

The recruitment of neutrophils to sites of localized injury or infection is initiated by changes on the surface of endothelial cells located in proximity to tissue damage. Inflammatory mediators, such as TNF-α, increase surface expression of adhesive ligands and receptors on the endothelial surface to which neutrophils tether and adhere. Neutrophils then transit through the activated endothelium to reach sites of tissue injury with little lasting vascular injury. However, in cases of sepsis, the interaction of endothelial cells with highly activated neutrophils can cause damage vascular damage. The identification of molecules that are essential for neutrophil diapedesis may reveal targets of therapeutic opportunity for preservation of endothelial function in the presence of critical illness. We tested the hypothesis that inhibition of neutrophil β1 integrin Very Late Antigen-3 (VLA-3; α3β1) and/or inhibition of the Tetraspanin (TM4) family member CD151 would protect against neutrophil-mediated loss of endothelial function. Blood was obtained from septic patients or healthy donors. Neutrophils were purified and aliquots were treated with/without proinflammatory molecules. Confluent Human Umbilical Vascular Endothelial Cells (HUVECs) were activated with tumor necrosis factor (TNF-α). Electric Cell Impedance Sensing (ECIS) was used to determine monolayer resistance over time after the addition of neutrophils that were treated with blocking antibodies against VLA-3 and/or CD151 or isotype controls. Groups (depending on relevancy) were analyzed by Mann-Whitney test, Wilcoxon test, or repeated measures one-way analysis of variance (ANOVA). Neutrophils from septic patients and neutrophils activated ex vivo reduced endothelial monolayer resistance to a greater extent than neutrophils from healthy donors. Antibody blockade of VLA-3 and/or CD151 significantly reduced activation-associated endothelial damage. Similar findings were demonstrated on fibronectin, collagen I, collagen IV and laminin suggesting that neutrophil surface VLA-3 and CD151 are responsible for endothelial damage regardless of substrata and are likely to be operative in all bodily tissues. This report identifies VLA-3 and CD151, on the activated human neutrophil that are responsible for damage to endothelial function. Targeting these molecules in vivo may demonstrate preservation of organ function during critical illness.

Relative and Temporal Efficacy of the First and Second Covid 19 Booster Vaccine (3rd And 4th Dose) to Prevent Symptomatic Infection from December 2021 to October 2023 in a General Medicine Office in Toledo (Spain)

Background: The effectiveness of COVID-19 vaccines in preventing serious infection and death is established, but their protection against infection is less certain. Additionally, their effectiveness diminishes over time. Furthermore, the evolution of the effectiveness of different booster doses of the vaccine against COVID-19, to prevent symptomatic infection in real life during the pandemic and the subsequent endemic, is not clearly documented. Objective: To compare the effectiveness of the 3rd and 4th vaccine boosters against COVID-19 in preventing symptomatic COVID-19 infection during both the pandemic and the subsequent endemic phase. Methodology: A comparative secondary analysis of the vaccine’s effectiveness against symptomatic COVID-19 infection (calculated as: 1 – (COVID-19 cases with vaccine doses / COVID-19 cases without vaccine dose) × 100) based on a prospective study from December 2021 to October 2023 in a general medicine office was conducted. The first booster dose was administered with monovalent mRNA vaccines, and the second booster with bivalent mRNA vaccines. Results: From December 2021 to February 2022, the effectiveness of the primer vaccine booster was 60% when administered &gt;= 15 days versus &lt;15 days before infection, and 36% when administered &gt;= 29 days versus &lt; 29 days before infection. From October 2022 to February 2023, the effectiveness of the vaccine’s 4th dose was 84%. From October 2022 to October 2023, the effectiveness of the 4th dose of bivalent mRNA vaccine in preventing reinfections was 30%. Conclusion: In the general practice setting in Toledo, Spain, the effectiveness of the first booster with mRNA vaccines against SARS-CoV-2 primary infection and symptomatic COVID-19 waned over time, but protection remained high with the second bivalent booster. However, the booster vaccine’s effectiveness is more modest in preventing symptomatic reinfections. Overall, completing the booster vaccination is worthwhile.

A hybrid transmission model for Plasmodium vivax accounting for superinfection, immunity and the hypnozoite reservoir

Malaria is a vector-borne disease that exacts a grave toll in the Global South. The epidemiology of Plasmodium vivax, the most geographically expansive agent of human malaria, is characterised by the accrual of a reservoir of dormant parasites known as hypnozoites. Relapses, arising from hypnozoite activation events, comprise the majority of the blood-stage infection burden, with implications for the acquisition of immunity and the distribution of superinfection. Here, we construct a novel model for the transmission of P. vivax that concurrently accounts for the accrual of the hypnozoite reservoir, (blood-stage) superinfection and the acquisition of immunity. We begin by using an infinite-server queueing network model to characterise the within-host dynamics as a function of mosquito-to-human transmission intensity, extending our previous model to capture a discretised immunity level. To model transmission-blocking and antidisease immunity, we allow for geometric decay in the respective probabilities of successful human-to-mosquito transmission and symptomatic blood-stage infection as a function of this immunity level. Under a hybrid approximation—whereby probabilistic within-host distributions are cast as expected population-level proportions—we couple host and vector dynamics to recover a deterministic compartmental model in line with Ross-Macdonald theory. We then perform a steady-state analysis for this compartmental model, informed by the (analytic) distributions derived at the within-host level. To characterise transient dynamics, we derive a reduced system of integrodifferential equations, likewise informed by our within-host queueing network, allowing us to recover population-level distributions for various quantities of epidemiological interest. In capturing the interplay between hypnozoite accrual, superinfection and acquired immunity—and providing, to the best of our knowledge, the most complete population-level distributions for a range of epidemiological values—our model provides insights into important, but poorly understood, epidemiological features of P. vivax.

Comparison on the Effectiveness and Safety of Transseptal Suturing Versus Intranasal Splints After Septoplasty: A Systematic Review and Meta-analysis.

The application of transseptal suturing as an alternative to intranasal splints in preventing postoperative complications, such as synechia, and maintaining nasal septal stability following Septoplasty, remains controversial. This meta-analysis aims to systematically compare the effectiveness and safety of transseptal suturing with intranasal splints after Septoplasty. A comprehensive systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. The review included randomized clinical trials (RCTs) identified through a database search in July 2023, comparing postoperative complications following Septoplasty with the transseptal suturing technique versus intranasal splints. Eight published RCTs involving 570 participants were included in the meta-analysis. The analysis revealed no significant difference between the transseptal suturing and intranasal splint techniques following Septoplasty in postoperative complications, including postoperative hemorrhage, synechia, septal hematoma, septal perforation, local infection, crusting, and residual septal deviation. Transseptal suturing can be applied following Septoplasty as an alternative to intranasal splints without increasing the rate of postoperative complications. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

IgG and IgM responses to the Plasmodium falciparum asexual stage antigens reflect respectively protection against malaria during pregnancy and infanthood.

Plasmodium falciparum malaria is a public health issue mostly seen in tropical countries. Until now, there is no effective malaria vaccine against antigens specific to the blood-stage of P. falciparum infection. Because the pathogenesis of malarial disease results from blood-stage infection, it is essential to identify the most promising blood-stage vaccine candidate antigens under natural exposure to malaria infection. A cohort of 400 pregnant women and their infants was implemented in South Benin. An active and passive protocol of malaria surveillance was established during pregnancy and infancy to precisely ascertain malaria infections during the follow-up. Twenty-eight antibody (Ab) responses specific to seven malaria candidate vaccine antigens were repeatedly quantified during pregnancy (3 time points) and infancy (6 time points) in order to study the Ab kinetics and their protective role. Abs were quantified by ELISA and logistic, linear and cox-proportional hazard model were performed to analyse the associations between Ab responses and protection against malaria in mothers and infants, taking into account socio-economic factors and for infants an environmental risk of exposure. The levels of IgM against MSP1, MSP2 and MSP3 showed an early protective response against the onset of symptomatic malaria infections starting from the 18th month of life, whereas no association was found for IgG responses during infancy. In women, some IgG responses tend to be associated with a protection against malaria risk along pregnancy and at delivery, among them IgG3 against GLURP-R0 and IgG2 against MSP1. The main finding suggests that IgM should be considered in vaccine designs during infanthood. Investigation of the functional role played by IgM in malaria protection needs further attention.

Investigating incidence of and factors associated with SARS-CoV-2 infection over a nine-month period in a highly-vaccinated healthcare worker cohort.

Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection. This risk persists despite the implementation of mitigating factors, including vaccination. The ongoing impact of incident SARS-CoV-2 infection and symptomatic COVID-19 disease in vaccinated healthcare workers is poorly understood. We aimed to describe the epidemiology of incident SARS-CoV-2 infections, as well as investigating the serological, clinical and demographic factors associated with developing infection. This was a multi-centre prospective longitudinal study followed a HCW cohort over a nine-month period. Spike and nucleocapsid SARS-CoV-2 antibodies were measured at enrolment. Vaccination status, demographics, and medical history were collated. Incident infection over the study period was recorded. Multivariable regression models investigated factors associated with nucleocapsid antibody status, incident infection, and symptomatic infection. 1,260 participants took part, of whom n = 1,006 were anti-nucleocapsid antibody positive. Negative anti-nucleocapsid antibody was associated with older age and having a known SARS-CoV-2 acquisition risk. There were n = 274 (22%) incident infections, with n = 225 (87%) diagnosed using antigen tests. Incident infections were associated with lower anti-nucleocapsid titres, increased time since previous SARS-CoV-2 infection, and having a known acquisition risk, but were not associated with vaccination status. This study demonstrates a high rate of incident SARS-CoV-2 infection amongst healthcare workers, despite broad vaccine coverage. There is a shift in diagnostics, from PCR to antigen testing. We identify at-risk groups for incident infection, and these should continue be targeted as part of risk reduction campaigns. Vaccination status and prior infection status alone are not surrogates for protection.

COMPARISON BETWEEN DIFFERENT TRANSRADIAL ARTERY HEMOSTASIS PROTOCOLS IN LIGURIAN CARDIOLOGIES

Abstract Background Transradial artery access (TRA) for coronary angiography and percutaneous coronary intervention is associated with lower bleeding and vascular complications than transfemoral artery access. In our hospital, TRA is widely used and hemostasis is usually achieved using TRBand device. We used to remove the device in about 10 hours according to our protocol. Aims The aim of this study is to describe and compare different TRA hemostasis protocols in order to understand if a shorter protocol could be more effective. Methods This is an observational study performed in all Hospitals of our region (Liguria). All Cardiology Departments were included in this analysis. We requested to all to self–refer: a) which radial hemostasis device was used; b) which deflation protocol (DP) was used. c) If they usually report and analyze adverse events. Adverse events are described as: bleeding, hematoma, ecchymosis, skin damage, local infection, pseudoaneurysm, or artery occlusion. RESULTS In Liguria there are 9 Cardiology Departments with Cath Lab (CL); 8 of them accepted to participate. All the Cath Labs use the TRBAND device but the deflation protocols are very different. 5 Cath Labs follows the DP suggested by the manufacturer. Only 2 CL adopted different DP if and higher dose of heparin was administered. Only one report bleedings or any delete in the DP. None analyze periodically the incidence of adverse events. Conclusions There are different methods to achieve radial hemostasis furthermore with the same device different deflating protocols are used. Further studies are necessary to evaluate the best DP. Regular audits must be strongly suggested in all Cardiology Departments in order to monitorate and improve the adverse events.