"Minimally symptomatic" congenital cytomegalovirus infection: latest data and emerging concepts.

PURPOSE OF REVIEW: Universal and targeted screening of newborns for congenital cytomegalovirus (CMV) infection is increasing globally. Questions remain concerning the management of infants who have been identified with congenital CMV infection, especially those with "minimally symptomatic" or clinically inapparent infection. Our objective is to discuss current management of CMV-infected neonates with a focus on less affected infants with or without sensorineural hearing loss (SNHL). RECENT FINDINGS: Valganciclovir is being prescribed increasingly in neonates with congenital CMV infection for improvement in hearing outcomes through 2 years of age. Treatment initiated in the first month of age is recommended for clinically apparent disease. A recent study showed hearing improvement at 18-22 months of age when therapy was initiated at age 1-3 months in infants with clinically inapparent CMV infection and isolated SNHL. SUMMARY: Antiviral therapy with either ganciclovir or valganciclovir has shown moderate benefit in prevention of hearing deterioration among infants with clinically apparent CMV infection or isolated SNHL. Sustainability of benefit beyond 2 years of age remains unknown. At present, infants with clinically inapparent CMV infection (normal complete evaluation including hearing) should not receive antiviral therapy. All CMV-infected infants require close audiological and neurodevelopmental follow-up.

The influence of frequency and gravity on the orientation of active metallo-dielectric Janus particles translating under a uniform applied alternating-current electric field.

Theoretical and numerical models of active Janus particles commonly assume that the metallo-dielectric interface is parallel to the driving applied electric field. However, our experimental observations indicate that the equilibrium angle of orientation of electrokinetically driven Janus particles varies as a function of the frequency and voltage of the applied electric field. Here, we quantify the variation of the orientation with respect to the electric field and demonstrate that the equilibrium position represents the interplay between gravitational, electrostatic and electrohydrodynamic torques. The latter two categories are functions of the applied field (frequency, voltage) as well as the height of the particle above the substrate. Maximum departure from the alignment with the electric field occurs at low frequencies characteristic of induced-charge electrophoresis and at low voltages where gravity dominates the electrostatic and electrohydrodynamic torques. The departure of the interface from alignment with the electric field is shown to decrease particle mobility through comparison of freely suspended Janus particles subject only to electrical forcing and magnetized Janus particles in which magnetic torque is used to align the interface with the electric field. Consideration of the role of gravitational torque and particle-wall interactions could account for some discrepancies between theory, numerics and experiment in active matter systems.

Induced-charge electrophoresis of a tilted metal nanowire near an insulating wall.

Electric fields are commonly used to control the orientation and motion of microscopic metal particles in aqueous suspensions. For example, metallodielectric Janus spheres are propelled by the induced-charge electro-osmotic flow occurring on their metallic side, the most common case in electrokinetics of exploiting symmetry breaking of surface properties for achieving net particle motion. In this work, we demonstrate that a homogeneous metal rod can translate parallel to a dielectric wall as a result of the hydrodynamic wall-particle interaction arising from the induced-charge electro-osmosis on the rod surface. The applied electric field could be either dc or low-frequency ac. The only requirement for a nonvanishing particle velocity is that the axis of the rod be inclined with respect to the wall, i.e., it cannot be neither parallel nor perpendicular. We show numerical results of the rod velocity as a function of rod orientation and distance to the wall. The maximum particle velocity is found for an orientation of between ∼30^{∘} and ∼50^{∘}, depending on the position and aspect ratio of the cylinder. Particle velocities of up to tens of µm/s are predicted for typical conditions in electrokinetic experiments.

Effectiveness of mRNA booster doses in preventing infections and hospitalizations due to SARS-CoV-2 and its dominant variant over time in Valencian healthcare workers, Spain.

OBJECTIVE: This study aimed to evaluate the effectiveness of SARS-CoV-2 mRNA vaccines in preventing infection and hospitalization among healthcare workers (HCWs) in the Valencian Community (Spain), considering vaccination timing, dose number, and predominant variant. METHODS: A test-negative case-control design estimated vaccine effectiveness against symptomatic disease and hospitalization due to SARS-CoV-2. HCWs who underwent PCR or antigen testing for SARS-CoV-2 from January 2021 to March 2022 were included. Cases had a positive diagnostic test, while controls had negative tests. Adjusted vaccine effectiveness (aVE) was calculated using the formula: aVE = (1 - Odds ratio) × 100. RESULTS: During the Delta variant's predominance, aVE against infection within 12-120 days post-second dose was 64.8 % (BNT162b2) and 59.4 % (mRNA-1273), declining to 21.2 % and 42.2 %, respectively, after 120 days. For the Omicron variant, aVE within 12-120 days post-second dose was 61.1 % (BNT162b2) and 85.1 % (mRNA-1273), decreasing to 36.7 % and 24.9 %, respectively, after 120 days. After a booster dose of mRNA-1273, aVE was 64.0 % (BNT162b2 recipients) and 65.9 % (initial mRNA-1273 recipients). Regardless of variant, aVE for hospitalization prevention after 2 doses was 87.0 % (BNT162b2) and 89.0 % (mRNA-1273). CONCLUSION: The administration of two doses of Moderna-mRNA-1273 against SARS-CoV-2 in HCWs proved to be highly effective in preventing infections and hospitalizations in the first 120 days after the second dose during the predominance of the Omicron variant. The decline in VE after 120 days since the administration of the second dose was significantly restored by the booster dose administration. This increase in VE was greater for the Pfizer vaccine. COVID-19 hospitalization prevention remained stable with both mRNA vaccines throughout the study period.

Concentration-polarization electroosmosis for particle fractionation.

Concentration-polarization electroosmosis (CPEO) refers to steady-state electroosmotic flows around charged dielectric micro-particles induced by low-frequency AC electric fields. Recently, these flows were shown to cause repulsion of colloidal particles from the wall of a microfluidic channel when an electric field is applied along the length of the channel. In this work, we exploit this mechanism to demonstrate fractionation of micron-sized polystyrene particles and bacteria in a flow-focusing device. The results are in agreement with predictions of the CPEO theory. The ease of implementation of CPEO-based fractionation in microfluidics makes it an ideal candidate for combining with current techniques commonly used to generate particle lift, such as inertial or viscoelastic focusing, requiring no extra fabrication steps other than inserting two electrodes.

Performance status at the time of lung retransplant predicts long-term function.

BACKGROUND: Lung retransplantation is offered to select patients with chronic allograft dysfunction. Given the increased risk of morbidity and mortality conferred by retransplantation, post-transplant function should be considered in the decision of who and when to list. The aim of this study is to identify predictors of post-operative disability in patients undergoing lung retransplantation. METHODS: Data were collected from the UNOS national dataset and included all patients who underwent lung retransplant from May 2005-March 2023. Pre- and post-operative function was reported by the Karnofsky Performance Status (KPS) and patients were stratified based on their needs. Cumulative link mixed effects models identified associations between pre-transplant variables and post-transplant function. RESULTS: A total of 1275 lung retransplant patients were included. After adjusting for between-group differences, pre-operative functional status was predictive of post-transplant function; patients requiring Total Assistance ( n = 740) were 74% more likely than No/Some Assistance patients (n = 535) to require more assistance in follow-up (OR 1.74, 95% CI 1.13-2.68, p = .012). Estimated one year survival of Total Assistance patients is lower than No/Some Assistance Recipients (72% vs. 82%, CI 69%-75%; 79%-86%) but similar to overall re-transplant survival (76%, CI 74%-79%). CONCLUSION: Both survival and regain of function in patients requiring Total Assistance prior to retransplant may be higher than previously reported. Pre-operative functional status is predictive of post-operative function and should weigh in the selection, timing and post-operative care of patients considered for lung retransplantation.

Adherence to quality indicators for emergency department treatment of acute poisoning according to patient sex. / Grado de cumplimiento de los indicadores de calidad según el sexo del paciente en las intoxicaciones agudas en urgencias.

OBJECTIVES: To study differences in the emergency department treatment of acute poisoning according to biological sex of patients and to assess adherence to care quality indicators. MATERIAL AND METHODS: Retrospective observational study including all cases of acute poisoning diagnosed in patients over the age of 14 years treated in a tertiary care hospital emergency department over a period of 4 years. We analyzed demographic variables, substance type and reason for acute poisoning, degree of adherence to quality indicators, and discharge destination. RESULTS: A total of 1144 cases were included; 710 patients (62.1%) were female and 434 (37.9%) were male. The proportion of deliberate self-poisoning was higher in females (52.3% vs 41.4% in males; P .001); unintentional poisoning was less frequent in females (in 24.9% vs in 30.3% of males; P = .047). Benzodiazepine poisoning was more frequent in females (in 49.6% vs 41.2%; P = .007). Street drug and alcohol poisoning was less common in females. Adherence to quality indicators was high (> 85%) for both sexes. CONCLUSION: The epidemiologic profile of poisoning is different in females and males. General emergency department adherence to quality indicators can be considered optimal. We detected no qualitative sex-related differences in the care of patients with acute poisoning.

OBJETIVO: Estudiar las diferencias dependiendo del sexo en la atención de pacientes con intoxicaciones agudas en urgencias y en el grado de cumplimiento de los indicadores de calidad (IC). METODO: Estudio observacional y retrospectivo, que incluyó todos los casos de intoxicación aguda de pacientes mayores de 14 años atendidos en el servicio de urgencias de un hospital terciario durante 4 años. Se analizaron variables demográficas, tipo de tóxicos y causa de la intoxicación, el grado de cumplimiento de los IC y destino al alta. RESULTADOS: Se registraron 1.144 casos, un 62,1% (n = 710) eran mujeres. Las mujeres tuvieron mayor número de intoxicaciones voluntarias (52,3% vs 41,4%; p 0,001) y menos de manera accidental (24,9% vs 30,3%; p = 0,047). Los fármacos más frecuentes en mujeres fueron las benzodiacepinas (49,6% vs 41,2%; p = 0,007), y las intoxicaciones por drogas de abuso y alcohol fueron menores que en hombres. Hubo un alto grado de cumplimiento en la mayoría de los IC (> 85%) en ambos sexos. CONCLUSIONES: El perfil epidemiológico de la intoxicación aguda en mujeres es diferente al de los hombres. En general se puede considerar como óptimo el cumplimiento de los IC en urgencias. No existen diferencias cualitativas en la asistencia del paciente intoxicado con respecto a su sexo.

Impact of COVID-19 on the degree of compliance with hand hygiene: a repeated cross-sectional study.

Hand hygiene (HH) is the paramount measure used to prevent healthcare-associated infections. A repeated cross-sectional study was undertaken with direct observation of the degree of compliance on HH of healthcare personnel during the SARS-CoV-2 pandemic. Between, 2018-2019, 9,083 HH opportunities were considered, and 5,821 in 2020-2022. Chi squared tests were used to identify associations. The crude and adjusted odds ratios were used along with a logistic regression model for statistical analyses. Compliance on HH increased significantly (p < 0.001) from 54.5% (95% CI: 53.5, 55.5) to 70.1% (95% CI: 68.9, 71.2) during the COVID-19 pandemic. This increase was observed in four of the five key moments of HH established by the World Health Organization (WHO) (p < 0.05), except at moment 4. The factors that were significantly and independently associated with compliance were the time period considered, type of healthcare-personnel, attendance at training sessions, knowledge of HH and WHO guidelines, and availability of hand disinfectant alcoholic solution in pocket format. Highest HH compliance occurred during the COVID-19 pandemic, reflecting a positive change in healthcare-personnel's behaviour regarding HH recommendations.

Impact of the COVID-19 Pandemic on Influenza Vaccination Coverage of Healthcare Personnel in Alicante, Spain.

Influenza is a health problem and vaccination is the most effective measure to prevent it. The objective of this study was to evaluate the impact of the COVID-19 pandemic on vaccination coverage (VC) against influenza in healthcare workers (HCWs). A cross-sectional study was conducted at the Dr. Balmis University General Hospital in the province of Alicante (Spain), in which vaccination data were collected retrospectively. Adverse effects (AEs) were detected via telephone call between 15 and 30 days after vaccination. The existence of significant changes in VC between the different seasons studied was evaluated using Chi square with a statistical significance level of p < 0.05. A total of 8403 HCWs vaccinated throughout the different seasons were studied. The vaccination coverage of HCWs for influenza pre-COVID-19 pandemic (2019/20 season) was 51.9%; increased during the pandemic to 67.9% (2020/21 season) and 65.5% (2021/22 season); and, after the pandemic, it decreased to 42.7% (2022/23 season) (p < 0.05). The most frequent reason for vaccination during the periods evaluated was "self-protection", followed by "protection of patients" and "protection of family members". Of all HCWs evaluated, 26.6% (1460/5493) reported at least one AE. During the COVID-19 pandemic, HCWs' influenza vaccination coverage fluctuated considerably. There has been an increase in VC during the most critical moments of the pandemic, both in the 2020/21 and 2021/22 seasons, which has, subsequently, decreased in the 2022/2023 season, to levels below pre-pandemic (2019/2020 season), which justifies implementing specific measures to recover VC in Spain.

Influence of cardiac diagnosis on outcomes of pediatric heart-lung transplantation.

OBJECTIVE: Pediatric Heart-lung transplant (HLTX) is performed for endstage congenital heart disease (CHD) with irreversible pulmonary hypertension or non-congenital heart disease (NCHD) with end-stage heart and lung disease. CHD could influence the outcomes of HTLX due to increased complexity of the operation as compared to NCHD. In this study we evaluated the influence of cardiac diagnosis on outcomes of pediatric HTLX. METHODS: The UNOS database (1987-2022) was queried for primary HTLX in patients <18 years. The data were extracted for demographics, pretransplant characteristics, post-transplant outcomes, and analyzed for the impact of cardiac diagnosis on post-transplant outcomes. Standard statistical tests were used. Survival was compared using the Kaplan-Meier method. RESULTS: Ninety of the 213 patients who underwent HLTX had CHD. There were no demographic differences. Heart listing status was similar but with a higher LAS score for NCHD. NCHD had higher pre-operative life support use (mechanical ventilation, inotropes or dialysis) but the use of ECMO as a bridge to transplantation was similar. Wait-list times were longer for CHD. The ischemic times were similar. Post-transplant dialysis, stroke, prolonged mechanical ventilation, and rejection were similar. Survival at 30-days, 1-year, and long-term survival at 17 years was similar. Non-survivors at 30-days post-transplant were on life support, used ECMO as a bridge, had lower wait-list times, longer ischemic times and had strokes. Non-survivors at 1-year had similar factors in addition to a higher dialysis use. CONCLUSION: Cardiac diagnosis had no impact on outcomes after Pediatric HLTX. Patients on life support or ECMO before transplantation were transplanted faster but with lower survival.

Grado de cumplimiento de los indicadores de calidad según el sexo del paciente en las intoxicaciones agudas en urgencias / Adherence to quality indicators for emergency department treatment of acute poisoning according to patient sex

Objetivos. Estudiar las diferencias dependiendo del sexo en la atención de pacientes con intoxicaciones agudas en urgencias y en el grado de cumplimiento de los indicadores de calidad (IC). Método. Estudio observacional y retrospectivo, que incluyó todos los casos de intoxicación aguda de pacientes mayores de 14 años atendidos en el servicio de urgencias de un hospital terciario durante 4 años. Se analizaron variables demográficas, tipo de tóxicos y causa de la intoxicación, el grado de cumplimiento de los IC y destino al alta. Resultados. Se registraron 1.144 casos, un 62,1% (n = 710) eran mujeres. Las mujeres tuvieron mayor número de intoxicaciones voluntarias (52,3% vs 41,4%; p < 0,001) y menos de manera accidental (24,9% vs 30,3%; p = 0,047). Los fármacos más frecuentes en mujeres fueron las benzodiacepinas (49,6% vs 41,2%; p = 0,007), y las intoxicaciones por drogas de abuso y alcohol fueron menores que en hombres. Hubo un alto grado de cumplimiento en la mayoría de los IC (> 85%) en ambos sexos. Conclusiones. El perfil epidemiológico de la intoxicación aguda en mujeres es diferente al de los hombres. En general se puede considerar como óptimo el cumplimiento de los IC en urgencias. No existen diferencias cualitativas en la asistencia del paciente intoxicado con respecto a su sexo. (AU)

Objective. To study differences in the emergency department treatment of acute poisoning according to biological sex of patients and to assess adherence to care quality indicators. Methods. Retrospective observational study including all cases of acute poisoning diagnosed in patients over the age of 14 years treated in a tertiary care hospital emergency department over a period of 4 years. We analyzed demographic variables, substance type and reason for acute poisoning, degree of adherence to quality indicators, and discharge destination. Results. A total of 1144 cases were included; 710 patients (62.1%) were female and 434 (37.9%) were male. The proportion of deliberate self-poisoning was higher in females (52.3% vs 41.4% in males; P < .001); unintentional poisoning was less frequent in females (in 24.9% vs in 30.3% of males; P = .047). Benzodiazepine poisoning was more frequent in females (in 49.6% vs 41.2%; P = .007). Street drug and alcohol poisoning was less common in females. Adherence to quality indicators was high (> 85%) for both sexes. Conclusions. The epidemiologic profile of poisoning is different in females and males. General emergency department adherence to quality indicators can be considered optimal. We detected no qualitative sex-related differences in the care of patients with acute poisoning. (AU)

Infección leve por SARS-CoV-2 en pacientes vulnerables: implantación de una vía clínica de tratamiento precoz / Mild SARS-CoV-2 infection in vulnerable patients: Implementation of a clinical pathway for early treatment

Introducción: El objetivo del manuscrito es describir la vía clínica de tratamiento precoz de pacientes con infección aguda por SARS-CoV-2 y evaluar los primeros resultados de su implementación. Métodos: Estudio descriptivo y retrospectivo de la implementación de una vía clínica de tratamiento en pacientes no hospitalizados (del 1 de enero al 30 de junio de 2022). Elaboración de vía clínica: sistemas de detección y derivación desde Atención Primaria, Servicio de Urgencias, especialidades médicas y sistema de detección automatizada; evaluación clínica y administración de tratamiento en hospital de día COVID-19, y seguimiento clínico posterior. Variables explicativas: demográficas, comorbilidad, estado vacunal, vías de derivación y administración de tratamiento. Variables de resultado: hospitalización y muerte a los 30 días, toxicidad grado 2-3 relacionada con el tratamiento. Resultados: Se administró tratamiento a 262 pacientes (53,4% mujeres, mediana de edad 60 años). Criterio de indicación de tratamiento: inmunosupresión (68,3%), y la combinación de edad, estado vacunal y comorbilidad en el resto. El 47,3% de los pacientes recibieron remdesivir, el 35,9% nirmatrelvir/ritonavir, el 13,4% sotrovimab y el 2,4% tratamiento combinado, con una mediana de 4 días tras el inicio de síntomas. El 6,1% de los pacientes precisó ingreso hospitalario, el 3,8% por progresión de COVID-19. Ningún paciente falleció. El 18,7% presentaron toxicidad grado 2-3: 89,8% disgeusia y sabor metálico relacionado con nirmatrelvir/ritonavir. Siete pacientes interrumpieron tratamiento por toxicidad. Conclusión: La creación e implementación de una vía clínica para pacientes no hospitalizados con infección por SARS-CoV-2 es efectiva y permite la accesibilidad temprana y la equidad de los tratamientos actualmente disponibles.(AU)

Introduction: The objective of this report is to describe the clinical pathway for early treatment of patients with acute SARS-CoV-2 infection and to evaluate the first results of its implementation. Methods: This is a descriptive and retrospective study of the implementation of a clinical pathway of treatment in outpatients (January 1 to June 30, 2022). Clinical pathway: detection and referral systems from Primary Care, Emergency services, hospital specialities and an automated detection system; clinical evaluation and treatment administration in the COVID-19 day-hospital and subsequent clinical follow-up. Explanatory variables: demographics, comorbidity, vaccination status, referral pathways and treatment administration. Outcome variables: hospitalization and death within 30 days, grade 2–3 toxicity related to treatment. Results: Treatment was administered to 262 patients (53.4% women, median age 60 years). The treatment indication criteria were immunosuppression (68.3%), and the combination of age, vaccination status and comorbidity in the rest; 47.3% of the patients received remdesivir, 35.9% nirmatrelvir/ritonavir, 13.4% sotrovimab and 2.4% combined treatment with a median of 4 days after symptom onset. Hospital admission was required for 6.1% of the patients, 3.8% related to COVID-19 progression. No patient died. Toxicity grade 2–3 toxicity was reported in 18.7%, 89.8% dysgeusia and metallic tasted related nirmatrelvir/ritonavir. Seven patients discontinued treatment due to toxicity. Conclusion: The creation and implementation of a clinical pathway for non-hospitalized patients with SARS-CoV-2 infection is effective and it allows early accessibility and equity of currently available treatments.(AU)

Ex vivo lung perfusion in donation after circulatory death: A post hoc analysis of the Normothermic Ex Vivo Lung Perfusion as an Assessment of Extended/Marginal Donors Lungs trial.

OBJECTIVE: Donation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multicenter setting. METHODS: This was an unplanned post hoc analysis of a multicenter, prospective, nonrandomized trial that took place during 2011 to 2017 with 3 years of follow-up. Patients were placed into 3 groups based off procurement strategy: brain-dead donor (control), brain-dead donor evaluated by EVLP, and DCD donors evaluated by EVLP. The primary outcomes were severe primary graft dysfunction at 72 hours and survival. Secondary outcomes included select perioperative outcomes, and 1-year and 3-years allograft function and quality of life measures. RESULTS: The DCD EVLP group had significantly higher incidence of severe primary graft dysfunction at 72 hours (P = .03), longer days on mechanical ventilation (P < .001) and in-hospital length of stay (P = .045). Survival at 3 years was 76.5% (95% CI, 69.2%-84.7%) for the control group, 68.3% (95% CI, 58.9%-79.1%) for the brain-dead donor group, and 60.7% (95% CI, 45.1%-81.8%) for the DCD group (P = .36). At 3-year follow-up, presence observed bronchiolitis obliterans syndrome or quality of life metrics did not differ among the groups. CONCLUSIONS: Although DCD EVLP allografts might not be appropriate to transplant in every candidate recipient, the expansion of their use might afford recipients stagnant on the waitlist a viable therapy.

Genomic and transcriptomic characterization of methylmercury detoxification in a deep ocean Alteromonas mediterranea ISS312.

Methylmercury (MeHg) is one of the most worrisome pollutants in marine systems. MeHg detoxification is mediated by merB and merA genes, responsible for the demethylation of MeHg and the reduction of inorganic mercury, respectively. Little is known about the biological capacity to detoxify this compound in marine environments, and even less the bacterial transcriptional changes during MeHg detoxification. This study provides the genomic and transcriptomic characterization of the deep ocean bacteria Alteromonas mediterranea ISS312 with capacity for MeHg degradation. Its genome sequence revealed four mer operons containing three merA gene and two merB gene copies, that could be horizontally transferred among distant related genomes by mobile genetic elements. The transcriptomic profiling in the presence of 5 µM MeHg showed that merA and merB genes are within the most expressed genes, although not all mer genes were equally transcribed. Besides, we aimed to identify functional orthologous genes that displayed expression profiles highly similar or identical to those genes within the mer operons, which could indicate they are under the same regulatory controls. We found contrasting expression profiles for each mer operon that were positively correlated with a wide array of functions mostly related to amino acid metabolism, but also to flagellar assembly or two component systems. Also, this study highlights that all merAB genes of the four operons were globally distributed across oceans layers with higher transcriptional activity in the mesopelagic deeper waters. Our study provides new insights about the transcriptional patterns related to the capacity of marine bacteria to detoxify MeHg, with important implications for the understanding of this process in marine ecosystems.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Pyrene-Appended Boronic Acids on Graphene Foam Electrodes Provide Quantum Capacitance-Based Molecular Sensors for Lactate.

Molecular recognition and sensing can be coupled to interfacial capacitance changes on graphene foam surfaces linked to double layer effects and coupled to enhanced quantum capacitance. 3D graphene foam film electrodes (Gii-Sens; thickness approximately 40 µm; roughness factor approximately 100) immersed in aqueous buffer media exhibit an order of magnitude jump in electrochemical capacitance upon adsorption of a charged molecular receptor based on pyrene-appended boronic acids (here, 4-borono-1-(pyren-2-ylmethyl)pyridin-1-ium bromide, or abbreviated T1). This pyrene-appended pyridinium boronic acid receptor is employed here as a molecular receptor for lactate. In the presence of lactate and at pH 4.0 (after pH optimization), the electrochemical capacitance (determined by impedance spectroscopy) doubles again. Lactic acid binding is expressed with a Hillian binding constant (Klactate = 75 mol-1 dm3 and α = 0.8 in aqueous buffer, Klactate = 460 mol-1 dm3 and α = 0.8 in artificial sweat, and Klactate = 340 mol-1 dm3 and α = 0.65 in human serum). The result is a selective molecular probe response for lactic acid with LoD = 1.3, 1.4, and 1.8 mM in aqueous buffer media (pH 4.0), in artificial sweat (adjusted to pH 4.7), and in human serum (pH adjusted to 4.0), respectively. The role of the pyrene-appended boronic acid is discussed based on the double layer structure and quantum capacitance changes. In the future, this new type of molecular capacitance sensor could provide selective enzyme-free analysis without analyte consumption for a wider range of analytes and complex environments.

Variation in risk-adjusted cardiac intensive care unit (CICU) length of stay and the association with in-hospital mortality: An analysis from the Critical Care Cardiology Trials Network (CCCTN) registry.

BACKGROUND: Previous studies have suggested that there is wide variability in cardiac intensive care unit (CICU) length of stay (LOS); however, these studies are limited by the absence of detailed risk assessment at the time of admission. Thus, we evaluated inter-hospital differences in CICU LOS, and the association between LOS and in-hospital mortality. METHODS: Using data from the Critical Care Cardiology Trials Network (CCCTN) registry, we included 22,862 admissions between 2017 and 2022 from 35 primarily tertiary and quaternary CICUs that captured consecutive admissions in annual 2-month snapshots. The primary analysis compared inter-hospital differences in CICU LOS, as well as the association between CICU LOS and all-cause in-hospital mortality using a Fine and Gray competing risk model. RESULTS: The overall median CICU LOS was 2.2 (1.1-4.8) days, and the median hospital LOS was 5.9 (2.8-12.3) days. Admissions in the longest tertile of LOS tended to be younger with higher rates of pre-existing comorbidities, and had higher Sequential Organ Failure Assessment (SOFA) scores, as well as higher rates of mechanical ventilation, intravenous vasopressor use, mechanical circulatory support, and renal replacement therapy. Unadjusted all-cause in-hospital mortality was 9.3%, 6.7%, and 13.4% in the lowest, intermediate, and highest CICU LOS tertiles. In a competing risk analysis, individual patient CICU LOS was correlated (r2 = 0.31) with a higher risk of 30-day in-hospital mortality. The relationship remained significant in admissions with heart failure, ST-elevation myocardial infarction and non-ST segment elevation myocardial infarction. CONCLUSIONS: In a large registry of academic CICUs, we observed significant variation in CICU LOS and report that LOS is independently associated with all-cause in-hospital mortality. These findings could potentially be used to improve CICU resource utilization planning and refine risk prognostication in critically ill cardiovascular patients.

Effectiveness of influenza vaccine in preventing severe cases of influenza: Season 2022/2023.

INTRODUCTION: Influenza poses a significant burden in terms of morbidity and mortality, with vaccination being one of the most effective measures for its prevention. Therefore, the aim of this study is to determine the effectiveness of the influenza vaccine in preventing cases of severe influenza in patients admitted to a tertiary hospital during the 2022/23 season. METHODS: Case-control study. All hospitalised patients with a positive result in an RT-PCR for influenza were included. Those who met the criteria for a severe case (pneumonia, sepsis, multi-organ failure, admission to ICU or exitus) were considered cases. Those who did not meet these criteria were considered controls. Vaccine effectiveness (VE) to prevent severe cases and its 95% confidence interval were calculated. RESULTS: A total of 403 patients were admitted with confirmed influenza. Of these, 98 (24.3%) developed severe influenza. Of the total, 50.6% were men and 47.1% were over 65 years of age. VE adjusted for influenza type, age and certain comorbidities was 40.6% (-21.9 to 71.1). In a segmented analysis, influenza vaccine was effective in preventing severe cases in all categories. It was particularly relevant in the 65+ age group (VEa = 60.9%; -2.0 to 85.0) and in patients with influenza A (VEa = 56.7%; 1.5-80.9). CONCLUSION: Influenza vaccination markedly reduced the occurrence of severe cases of influenza in hospitalised patients, therefore, it remains the main strategy to reduce morbidity and mortality and associated costs.

Unmasking the physiology of mercury detoxifying bacteria from polluted sediments.

Marine sediments polluted from anthropogenic activities can be major reservoirs of toxic mercury species. Some microorganisms in these environments have the capacity to detoxify these pollutants, by using the mer operon. In this study, we characterized microbial cultures isolated from polluted marine sediments growing under diverse environmental conditions of salinity, oxygen availability and mercury tolerance. Specific growth rates and percentage of mercury removal were measured in batch cultures for a selection of isolates. A culture affiliated with Pseudomonas putida (MERCC_1942), which contained a mer operon as well as other genes related to metal resistances, was selected as the best candidate for mercury elimination. In order to optimize mercury detoxification conditions for strain MERCC_1942 in continuous culture, three different dilution rates were tested in bioreactors until the cultures achieved steady state, and they were subsequently exposed to a mercury spike; after 24 h, strain MERCC_1942 removed up to 76% of the total mercury. Moreover, when adapted to high growth rates in bioreactors, this strain exhibited the highest specific mercury detoxification rates. Finally, an immobilization protocol using the sol-gel technology was optimized. These results highlight that some sediment bacteria show capacity to detoxify mercury and could be used for bioremediation applications.

Oral Valganciclovir Initiated Beyond 1 Month of Age as Treatment of Sensorineural Hearing Loss Caused by Congenital Cytomegalovirus Infection: A Randomized Clinical Trial.

OBJECTIVE: The objective of this study was to determine if valganciclovir initiated after 1 month of age improves congenital cytomegalovirus-associated sensorineural hearing loss. STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled phase 2 trial of 6 weeks of oral valganciclovir at US (n = 12) and UK (n = 9) sites. Patients of ages 1 month through 3 years with baseline sensorineural hearing loss were enrolled. The primary outcome was change in total ear hearing between baseline and study month 6. Secondary outcome measures included change in best ear hearing and reduction in cytomegalovirus viral load in blood, saliva, and urine. RESULTS: Of 54 participants enrolled, 35 were documented to have congenital cytomegalovirus infection and were randomized (active group: 17; placebo group: 18). Mean age at enrollment was 17.8 ± 15.8 months (valganciclovir) vs 19.5 ± 13.1 months (placebo). Twenty (76.9%) of the 26 ears from subjects in the active treatment group did not have worsening of hearing, compared with 27 (96.4%) of 28 ears from subjects in the placebo group (P = .09). All other comparisons of total ear or best ear hearing outcomes were also not statistically significant. Saliva and urine viral loads decreased significantly in the valganciclovir group but did not correlate with change in hearing outcome. CONCLUSIONS: In this randomized controlled trial, initiation of antiviral therapy beyond the first month of age did not improve hearing outcomes in children with congenital cytomegalovirus-associated sensorineural hearing loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01649869.