Prevalencia y factores de riesgo de infección por Staphylococcus aureus resistente ameticilina en niños / Prevalence and risk factors for methicillinresistant Staphylococcus aureus infection in children

Introducción. Los objetivos de este trabajo fueron conocer la prevalencia de infecciones por Staphylococcus aureus resistente a meticilina (SARM) en la población pediátrica de nuestro departamento de salud, describir los factores de riesgo para infección por SARM frente a las producidas por S. aureus sensible a meticilina (SASM) y conocer el perfil de sensibilidad antibiótica de los aislados de SARM y SASM. Pacientes y métodos. Se realizó un estudio retrospectivo descriptivo y analítico de las infecciones producidas por SARM frente a las producidas por SASM durante los años 2014 al 2018. Se estudiaron las variables predictoras de SARM mediante un modelo de regresión logística binaria. Resultados. Se identificaron 162 pacientes con infecciones por S. aureus, 15,4% resistentes a meticilina. Los porcentajes mayores de infección por SARM se dieron entre los niños que precisaron ingreso hospitalario (23,4%). En el análisis univariante alcanzaron significación estadística la necesidad de ingreso hospitalario, el antecedente de haber recibido tratamiento antibiótico en los 3 meses previos, el tipo de infección y el antecedente de infección o colonización previa por SARM. En el modelo de regresión logística la necesidad de ingreso hospitalario y el tratamiento antibiótico reciente mantuvieron significación estadística. Solo recibieron tratamiento antibiótico correcto el 26,7% de los niños que ingresaron con infección por SARM. Conclusiones. Nuestros resultados sugieren la necesidad de revisar las pautas de tratamiento empírico usando fármacos activos frente a SARM en las infecciones de probable origen estafilocócico que ingresen en el hospital en niños sobre todo si han recibido tratamiento antibiótico reciente. (AU)

Introduction. The objectives of this work were to know the prevalence of methicillin-resistant S. aureus (MRSA) infections in the paediatric population of our health department, to describe the risk factors for infection by MRSA compared to those produced by methicillin-susceptible S. aureus (MSSA) and to know the antibiotic sensitivity profile of MRSA and MSSA isolates. Material and methods. A retrospective, descriptive and analytical study of infections produced by MRSA versus those produced by MSSA was carried out during the years 2014 to 2018. Risk factors for MRSA infection were studied using a binary logistic regression model. Results, 162 patients with S. aureus infections were identified. Of these, 25 (15.4%) were MRSA. The highest percentages of MRSA infection occurred among children who required hospital admission (23.4%). In the univariate analysis the need of hospital admission, antibiotic treatment in the last 3 months, the kind of infection and past MRSA infection or colonisation reached statistical significance. However, only the need of hospital admission and antibiotic treatment in the last 3 months maintained statistical significance in the binary logistic regression model. Correct antibiotic treatment was only prescribed in 26.7% of the MRSA infection cases admitted to the hospital. Conclusions. Our results suggest the need to review empirical local treatment regimen using drugs active against MRSA in infections of probable staphylococcal origin admitted to the hospital, especially if they have received antibiotic treatment in the last 3 months. (AU)

Supervised Telerehabilitation and Home-based Respiratory Muscle Training for Post-COVID-19 Condition Symptoms: A Nested Qualitative Study Exploring the Perspectives of Participants in a Randomized Controlled Trial.

OBJECTIVE: The purpose of this study was to describe the experiences of individuals with post-COVID-19 condition symptoms who underwent a supervised telerehabilitation and home-based respiratory muscle training (TSHB-RMT) program. METHODS: A qualitative descriptive study was conducted. Participants were recruited using purposeful sampling. The inclusion criteria consisted of: patients aged over 18 years who presented persistent COVID-19 symptoms of fatigue and dyspnea for at least 3 months after the COVID-19 diagnosis. In total, 28 patients were included. In-depth interviews and researcher field notes were used to collect the data. A thematic analysis was performed. RESULTS: Three themes reflect the patients' perspective on the TSHB-RMT before the program (reasons for participating), during the treatment program, and upon completion of the study. Among the reasons for participation, participants highlighted the absence of improvement and treatment, and feeling abandoned and forgotten by the health system. The treatment required discipline on behalf of the patients. Mondays and Tuesdays were the most difficult days for performing the therapy and the physical therapist was perceived as a tool for adherence, change, and a source of validated information. The patients perceived positive effects quite soon, however, it was necessary to extend the follow-up after completing the program because they abandoned the program due to the lack of guidance for exercise supervision. CONCLUSIONS: This study described relevant aspects that physical therapist professionals should consider when providing TSHB-RMT treatment. IMPACT: TSHB-RMT requires discipline, perseverance, effort, and a commitment to the group. The physical therapist is perceived as the tool that facilitates adherence and participation. The effects are rapidly perceived, leading to improved self-confidence and autonomy, however, it is necessary to increase the follow-up time.

Immunogenicity of Monovalent mRNA-1273 and BNT162b2 Vaccines in Children Less Than 5 Years of Age.

BACKGROUND AND OBJECTIVES: The mRNA-based COVID-19 vaccines approved for use in children less than 5 years of age have different antigen doses and administration schedules that could affect vaccine immunogenicity and effectiveness. We sought to compare the strength and breadth of serum binding and neutralizing antibodies to SARS-CoV-2 elicited by monovalent mRNA-based COVID-19 vaccines in young children. METHODS: We conducted a prospective cohort study of children 6 months to 4 years of age who completed primary series vaccination with monovalent mRNA-1273 or BNT162b2 vaccines. Serum was collected one month after primary vaccine series completion for measurement of SARS-CoV-2-specific humoral immune responses, including antibody binding responses to Spike proteins from an ancestral strain (D614G) and major variants of SARS-CoV-2 and antibody neutralizing activity against D614G and Omicron subvariants (BA.1, BA.4/5). RESULTS: Of 75 participants, 40 (53%) received mRNA-1273 and 35 (47%) received BNT162b2. Children receiving either primary vaccine series developed robust and broad SARS-CoV-2-specific binding and neutralizing antibodies, including to Omicron subvariants. Children with a prior history of SARS-CoV-2 infection developed significantly higher antibody binding responses and neutralization titers to Omicron subvariants, consistent with the occurrence of identified infections during the circulation of Omicron subvariants in the region. CONCLUSIONS: Monovalent mRNA-1273 and BNT162b2 elicited similar antibody responses one month after vaccination in young children. Further, prior infection significantly enhanced the strength of antibody responses to Omicron subvariants. Future studies should evaluate incorporation of these vaccines into the standard childhood immunization schedule.

Risk factors for readmission after a cholecystectomy: a case-control study.

OBJECTIVE: The aim of this study was to assess the risk factors associated with 30-day hospital readmissions after a cholecystectomy. METHODS: We conducted a case-control study, with data obtained from UC-Christus from Santiago, Chile. All patients who underwent a cholecystectomy between January 2015 and December 2019 were included in the study. We identified all patients readmitted after a cholecystectomy and compared them with a randomized control group. Univariate and multivariate analyses were conducted to identify risk factors. RESULTS: Of the 4866 cholecystectomies performed between 2015 and 2019, 79 patients presented 30-day hospital readmission after the surgical procedure (1.6%). We identified as risk factors for readmission in the univariate analysis the presence of a solid tumor at the moment of cholecystectomy (OR = 7.58), high pre-operative direct bilirubin (OR = 2.52), high pre-operative alkaline phosphatase (OR = 3.25), emergency admission (OR = 2.04), choledocholithiasis on admission (OR = 4.34), additional surgical procedure during the cholecystectomy (OR = 4.12), and post-operative complications. In the multivariate analysis, the performance of an additional surgical procedure during cholecystectomy was statistically significant (OR = 4.24). CONCLUSION: Performing an additional surgical procedure during cholecystectomy was identified as a risk factor associated with 30-day hospital readmission.

OBJETIVO: El objetivo de este estudio fue evaluar los factores de riesgo asociados al reingreso hospitalario en los primeros 30 días post colecistectomía. MÉTODOS: Estudio de casos-controles con datos obtenidos del Hospital Clínico de la UC-Christus, Santiago, Chile. Se ­incluyeron las colecistectomías realizadas entre los años 2015-2019. Se consideraron como casos aquellos pacientes que reingresaron en los 30 primeros días posterior a una colecistectomía. Se realizó un análisis univariado y multivariado de diferentes posibles factores de riesgo. RESULTADOS: De un total de 4866 colecistectomías, 79 pacientes presentaron reingreso hospitalario. Los resultados estadísticamente significativos en el análisis univariado fueron; tumor sólido al momento de la colecistectomía (OR = 7.58) bilirrubina directa preoperatoria alterada (OR = 2.52), fosfatasa alcalina preoperatoria alterada (OR = 3.25), ingreso de urgencia (OR = 2.04), coledocolitiasis al ingreso (OR = 4.34) realización de otros procedimientos (OR = 4.12) y complicaciones postoperatorias. En el análisis multivariado sólo la realización de otro procedimiento durante la colecistectomía fue estadísticamente significativa (OR = 4.24). CONCLUSIÓN: La realización de otros procedimientos durante la colecistectomía es un factor de riesgo de reingreso hospitalario en los 30 días posteriores a la colecistectomía.

Assessing the implementation of a multi-component hypertension program in a Guatemalan under-resourced dynamic context: an application of the RE-AIM/PRISM extension for sustainability and health equity.

BACKGROUND: The COVID-19 pandemic necessitated rapid changes in healthcare delivery in Guatemala's public primary care settings. A new hypertension program, implemented as part of a type 2 hybrid trial since 2019, exemplifies an implementation effort amidst a changing context in an under-resourced setting. We assessed the implementation of an evidence-based intervention (EBI; protocol-based hypertension treatment) and one of its main implementation strategies (team-based collaborative care), raising implications for health equity and sustainability. We present innovative application of systems thinking visuals. METHODS: Conducting a convergent mixed methods analysis, we assessed implementation in response to contextual changes across five Ministry of Health (MoH) districts at the pandemic's onset. Utilizing quantitative programmatic data and qualitative interviews with stakeholders (n=18; health providers, administrators, study staff), we evaluated dimensions of "Reach, Effectiveness, Adoption, Implementation and Maintenance," RE-AIM (Reach, Implementation delivery + adaptations), and "Practical Robust Implementation and Sustainability Model," PRISM (Organizational perspective on the EBI, Fit, Implementation and sustainability infrastructure) frameworks. We assessed representativeness by comparing participants to census data. To assess implementation delivery, we built behavior-over-time (BOT) graphs with quantitative programmatic data (July 2019-July 2021). To assess adaptations and contextual changes, we performed matrix-based thematic qualitative analysis. We converged quantitative implementation delivery data + qualitative adaptations data in joint displays. Finally, we analyzed qualitative and quantitative results across RE-AIM/PRISM and health districts to identify equity and sustainability considerations. RESULTS: Contextual factors that facilitated program delivery included the perception that the EBI was beneficial, program champions, and staff communication. Key barriers to implementation delivery included competition with other primary care activities and limited implementation infrastructure (e.g., equipment, medications). Contextual changes related to COVID-19 hindered implementation delivery, threatened sustainability, and may have exacerbated inequities. However, adaptations that were planned enhanced implementation delivery and may have supported improved equity and sustainability. CONCLUSIONS: Recognition of an EBI's benefits and program champions are important for supporting initial uptake. The ability to plan adaptations amid rapid contextual changes has potential advantages for sustainability and equitable delivery. Systems thinking tools and mixed methods approaches may shed light on the relations between context, adaptations, and equitable and sustainable implementation. TRIAL REGISTRATION: NCT03504124.

The recruitment of TRiC chaperonin in rotavirus viroplasms correlates with virus replication.

Rotavirus (RV) replication takes place in the viroplasms, cytosolic inclusions that allow the synthesis of virus genome segments and their encapsidation in the core shell, followed by the addition of the second layer of the virion. The viroplasms are composed of several viral proteins, including NSP5, which serves as the main building block. Microtubules, lipid droplets, and miRNA-7 are among the host components recruited in viroplasms. We investigated the interaction between RV proteins and host components of the viroplasms by performing a pull-down assay of lysates from RV-infected cells expressing NSP5-BiolD2. Subsequent tandem mass spectrometry identified all eight subunits of the tailless complex polypeptide I ring complex (TRiC), a cellular chaperonin responsible for folding at least 10% of the cytosolic proteins. Our confirmed findings reveal that TRiC is brought into viroplasms and wraps around newly formed double-layered particles. Chemical inhibition of TRiC and silencing of its subunits drastically reduced virus progeny production. Through direct RNA sequencing, we show that TRiC is critical for RV replication by controlling dsRNA genome segment synthesis, particularly negative-sense single-stranded RNA. Importantly, cryo-electron microscopy analysis shows that TRiC inhibition results in defective virus particles lacking genome segments and polymerase complex (VP1/VP3). Moreover, TRiC associates with VP2 and NSP5 but not with VP1. Also, VP2 is shown to be essential for recruiting TRiC in viroplasms and preserving their globular morphology. This study highlights the essential role of TRiC in viroplasm formation and in facilitating virion assembly during the RV life cycle. IMPORTANCE: The replication of rotavirus takes place in cytosolic inclusions termed viroplasms. In these inclusions, the distinct 11 double-stranded RNA genome segments are co-packaged to complete a genome in newly generated virus particles. In this study, we show for the first time that the tailless complex polypeptide I ring complex (TRiC), a cellular chaperonin responsible for the folding of at least 10% of the cytosolic proteins, is a component of viroplasms and is required for the synthesis of the viral negative-sense single-stranded RNA. Specifically, TRiC associates with NSP5 and VP2, the cofactor involved in RNA replication. Our study adds a new component to the current model of rotavirus replication, where TRiC is recruited to viroplasms to assist replication.

Positive Outliers: A Mixed Methods Study of Resiliency to Childhood Obesity in High-Risk Neighborhoods.

OBJECTIVE: Despite the high prevalence of obesity and the clustering of risk by neighborhood, few studies have examined characteristics which promote healthy child weight in neighborhoods with high obesity risk. We aimed to identify protective factors for children living in neighborhoods with high obesity risk. METHODS: We identified neighborhoods with high obesity risk using geolocated electronic health record data with measured body mass index (BMI) from well child visits (2012-2017). We then recruited caregivers with children aged 5-13 years who lived in census tracts with mean child BMI percentile >72 (February 2020- August 2021). We used sequential mixed methods (quantitative surveys, qualitative interviews) to compare individual, interpersonal and perceived neighborhood factors among families with children at healthy weight (positive outliers, PO) vs. families with ≥1 child with overweight or obesity (controls). Regression models and comparative qualitative analysis were used to identify protective characteristics. RESULTS: Seventy-three caregivers participated in the quantitative phase (41% PO; 34% preferred Spanish) and twenty in the qualitative phase (50% PO; 50% preferred Spanish). Frequency of healthy caregiver behaviors was associated with being a PO (Family Health Behavior Scale Parent Score adjusted ß 3.67; 95% CI 0.52-6.81 and qualitative data). Protective factors also included caregivers' ability to minimize the negative health influences of family members and adhere to family routines. CONCLUSIONS: There were few differences between PO and control families. Support for caregiver healthy habits and adherence to healthy family routines emerged as opportunities for childhood obesity prevention in neighborhoods with high obesity risk. WHAT'S NEW: In neighborhoods with high risk of child obesity, families with healthy weight children and families with children with overweight/obesity are behaviorally and socially similar. Parental modeling and support for healthy behaviors across children's environments may promote healthy child weight.

Photofragmentation of cyclobutanone at 200 nm: TDDFT vs CASSCF electron diffraction.

To simulate a 200 nm photoexcitation in cyclobutanone to the n-3s Rydberg state, classical trajectories were excited from a Wigner distribution to the singlet state manifold based on excitation energies and oscillator strengths. Twelve singlet and 12 triplet states are treated using TD-B3LYP-D3/6-31+G** for the electronic structure, and the nuclei are propagated with the Tully surface hopping method. Using time-dependent density functional theory, we are able to predict the bond cleavage that takes place on the S1 surface as well as the ultrafast deactivation from the Rydberg n-3s state to the nπ*. After showing that triplet states and higher-lying singlet states do not play any crucial role during the early dynamics (i.e., the first 300 fs), the SA(6)-CASSCF(8,11)/aug-cc-pVDZ method is used as an electronic structure and the outcome of the non-adiabatic dynamic simulations is recomputed. Gas-phase ultrafast electron diffraction spectra are computed for both electronic structure methods, showing significantly different results.

A Preliminary Evaluation of Sex and Dietary Field Pea Effects on Sensory Characteristics of Dry-Cured Loins.

Two of the main issues related to cured meat products are castration to avoid boar taint and the hefty reliance on soybean meal to feed pigs. However, data on the effects of immunocastration in pigs and alternative crop protein feeds on the sensory traits and consumers' acceptance of dry-cured loin are still limited. A preliminary study was conducted on the effect of sex type (surgical castrated male pigs and immunocastrated male and female pigs, at approximately 140 kg in weight and 7 months of age) and animal diet (pea vs. soya) on dry-cured loins. The study involved a sensory evaluation of six treatments, with a 3 × 2 factorial design, conducted by trained panellists and untrained consumers in Spain (n = 126) and Portugal (n = 80). The consumers were also checked for their skatole sensitivity using a pure substance. The results showed that the pea-based diet was significantly different (p < 0.001) from the soy-based diet, as determined by a trained panel of surgically castrated male pigs, although the immunocastration treatments were not split. Dry-cured loin from immunocastrated male pigs fed with peas was considered tenderer and juicier (p < 0.05) than those fed soya-based diets. The untrained consumer panel scored higher on the sensory traits (flavour, juiciness, and overall liking) from the loin samples of surgically castrated male pigs fed a pea diet. All consumers scored similarly in boar taint detection. This study demonstrates the applicability of the pea-based diet for the feeding of pigs destined for cured meat and highlights immunocastration as a tool that does not compromise the skatole detection score.

Dendritic Cells in Cancer Immunology and Immunotherapy.

Cancer immunotherapy modulates the immune system, overcomes immune escape and stimulates immune defenses against tumors. Dendritic cells (DCs) are professional promoters of immune responses against tumor antigens with the outstanding ability to coordinate the innate and adaptive immune systems. Evidence suggests that there is a decrease in both the number and function of DCs in cancer patients. Therefore, they represent a strong scaffold for therapeutic interventions. DC vaccination (DCV) is safe, and the antitumoral responses induced are well established in solid tumors. Although the addition of checkpoint inhibitors (CPIs) to chemotherapy has provided new options in the treatment of cancer, they have shown no clinical benefit in immune desert tumors or in those tumors with dysfunctional or exhausted T-cells. In this way, DC-based therapy has demonstrated the ability to modify the tumor microenvironment for immune enriched tumors and to potentiate systemic host immune responses as an active approach to treating cancer patients. Application of DCV in cancer seeks to obtain long-term antitumor responses through an improved T-cell priming by enhancing previous or generating de novo immune responses. To date, DCV has induced immune responses in the peripheral blood of patients without a significant clinical impact on outcome. Thus, improvements in vaccines formulations, selection of patients based on biomarkers and combinations with other antitumoral therapies are needed to enhance patient survival. In this work, we review the role of DCV in different solid tumors with their strengths and weaknesses, and we finally mention new trends to improve the efficacy of this immune strategy.

Phenotypic, Technological, Safety, and Genomic Profiles of Gamma-Aminobutyric Acid-Producing Lactococcus lactis and Streptococcus thermophilus Strains Isolated from Cow's Milk.

Gamma-aminobutyric acid (GABA)-producing lactic acid bacteria (LAB) can be used as starters in the development of GABA-enriched functional fermented foods. In this work, four GABA-producing strains each of Lactococcus lactis and Streptococcus thermophilus species were isolated from cow's milk, and their phenotypic, technological, and safety profiles determined. Genome analysis provided genetic support for the majority of the analyzed traits, namely, GABA production, growth in milk, and the absence of genes of concern. The operon harboring the glutamate decarboxylase gene (gadB) was chromosomally encoded in all strains and showed the same gene content and gene order as those reported, respectively, for L. lactis and S. thermophilus. In the latter species, the operon was flanked (as in most strains of this species) by complete or truncated copies of insertion sequences (IS), suggesting recent acquisition through horizontal gene transfer. The genomes of three L. lactis and two S. thermophilus strains showed a gene encoding a caseinolytic proteinase (PrtP in L. lactis and PrtS in S. thermophilus). Of these, all but one grew in milk, forming a coagulum of good appearance and an appealing acidic flavor and taste. They also produced GABA in milk supplemented with monosodium glutamate. Two L. lactis strains were identified as belonging to the biovar. diacetylactis, utilized citrate from milk, and produced significant amounts of acetoin. None of the strains showed any noticeable antibiotic resistance, nor did their genomes harbor transferable antibiotic resistance genes or genes involved in toxicity, virulence, or pathogenicity. Altogether these results suggest that all eight strains may be considered candidates for use as starters or components of mixed LAB cultures for the manufacture of GABA-enriched fermented dairy products.

Readaptación funcional basada en ejercicio físico terapéutico en pacientes con COVID persistente (RECOVER) / Functional rehabilitation based on therapeutic exercise training in patients with postacute COVID syndrome (RECOVER)

Introduction and objectives Postacute COVID syndrome (PACS) is common after acute SARS-CoV-2 infection. One of the most frequent and disabling symptoms is exercise intolerance (EI). Recent evidence suggests that EI in PACS has a peripheral (metabolic-neuromuscular) origin, suggesting that exercise training may be an effective treatment. The aim of this study was to assess the role a therapeutic physical exercise program (TPEP) in PACS with EI. Method This single-center, open-label, randomized clinical trial compared an exercise training program (intervention group) with regular physical activity recommendations (control group) in patients with PACS and EI. The intervention group underwent an 8-week TPEP. The primary endpoint was improvement in functional capacity, assessed as the change in peak VO2. Results We included 50 participants with PACS (73% women, mean age 47±7.1 years). The intervention group showed a 15% improvement in peak VO2 (peak VO2 pre- and postintervention: 25.5±7.7mL/kg/min and 29.3±4.7 mL/kg/min; P <.001) and a 13.2% improvement in predicted values (92.1±14.3% and 108.4±13.4%; P <.001). No significant changes in VO2 values were observed in the control group. Unlike the control group, the intervention group also showed improvements in all secondary outcomes: quality of life scales, muscle power, maximum inspiratory power, metabolic flexibility, and body fat percentage. Conclusions The program improved functional capacity in patients with PACS and EI (AU)

Introducción y objetivos El síndrome de COVID persistente (SCP) es frecuente tras la infección aguda por SARS-CoV-2, y la intolerancia al ejercicio (IE) uno de los síntomas más frecuentes y limitantes. La evidencia reciente indica que el origen de los síntomas es periférico (muscular), por lo que el ejercicio físico podría ser un tratamiento eficaz. Este estudio evalúa la eficacia de un programa de ejercicio físico terapéutico (PEFT) en la mejora de la capacidad funcional de los pacientes con SCP e IE. Métodos Estudio aleatorizado, unicéntrico, controlado y abierto que compara un PEFT (grupo de intervención) con recomendaciones de actividad física estándar (grupo de control) en pacientes con SCP con IE. El grupo de intervención recibió 8 semanas de PEFT. El objetivo principal fue el cambio en la capacidad funcional medido mediante el consumo pico de oxígeno (VO2 pico). Resultados Se incluyó a un total de 50 pacientes con SCP (el 73% mujeres; media de edad, 47±7,1 años). El grupo de intervención presentó una mejora en el VO2 pico del 15% (VO2 pico inicial y final: 25,5±7,7 y 29,3±4,7ml/kg/min; p <0,001) y del 13,2% en valores del %VO2 máximo predicho (el 92,1±14,3% y el 108,4±13,4%; p <0,001), sin cambios significativos en el grupo de control. Todos los objetivos secundarios también mejoraron exclusivamente en el grupo de intervención: escalas de calidad de vida, potencia muscular desarrollada, potencia inspiratoria máxima, flexibilidad metabólica y porcentaje de grasa corporal. Conclusiones El PEFT mejora la capacidad funcional de los pacientes con SCP e IE (AU)

Survival and safety after neoadjuvant chemotherapy or upfront surgery for locally advanced colon cancer: meta-analysis.

BACKGROUND: Neoadjuvant chemotherapy is increasingly used to treat locally advanced (T3-4 Nx-2 M0) colon cancer due to its potential advantages over the standard approach of upfront surgery. The primary objective of this systematic review and meta-analysis was to analyse data from comparative studies to assess the impact of neoadjuvant chemotherapy on oncological outcomes. METHODS: A systematic review was conducted by searching the MEDLINE and Scopus databases. The search encompassed RCTs, propensity score-matched studies, and controlled prospective studies published up to 1 April 2023. As a primary objective, overall survival and disease-free survival were compared. As a secondary objective, perioperative morbidity, mortality, and complete resection were compared using the DerSimonian and Laird models. RESULTS: A total of seven studies comprising a total of 2120 patients were included. Neoadjuvant chemotherapy was associated with a reduction in the hazard of recurrence (HR 0.73, 95% c.i. 0.59 to 0.90; P = 0.003) and death (HR 0.67, 95% c.i. 0.54 to 0.83; P < 0.001) compared with upfront surgery. Additionally, neoadjuvant chemotherapy was significantly associated with higher 5-year overall survival (79.9% versus 72.6%; P < 0.001) and disease-free survival (73.1% versus 64.5%; P = 0.028) rates. No significant differences were observed in perioperative mortality (OR 0.97, 95% c.i. 0.28 to 3.33), overall complications (OR 0.95, 95% c.i. 0.77 to 1.16), or anastomotic leakage/intra-abdominal abscess (OR 0.88, 95% c.i. 0.60 to 1.29). However, neoadjuvant chemotherapy was associated with a lower risk of incomplete resection (OR 0.70, 95% c.i. 0.49 to 0.99). CONCLUSION: Neoadjuvant chemotherapy is associated with a reduced hazard of recurrence and death, as well as improved overall survival and disease-free survival rates, compared with upfront surgery in patients with locally advanced colon cancer.

Colon cancer is a common medical condition, the established treatment for which involves surgical resection followed by chemotherapy. However, a contemporary shift has led to the investigation of an alternative treatment sequence known as neoadjuvant chemotherapy, wherein chemotherapy precedes the surgery. This study critically assesses the efficacy of neoadjuvant chemotherapy compared with the standard treatment approach of surgery followed by chemotherapy. A systematic review of medical databases was undertaken to identify pertinent research publications on this subject matter. In total, seven studies encompassing data from 2120 patients were included in the analysis. Employing a meta-analysis methodology to synthesize the collective data from these studies, it was revealed that neoadjuvant chemotherapy was linked to higher rates of 5-year overall survival and disease-free survival, alongside a diminished hazard of both recurrence and death. Furthermore, no discernible differences in surgical complications or perioperative mortality were evident across the compared approaches.

The ELECLA trial: A multicentre randomised control trial on outcomes of neoadjuvant treatment on locally advanced colon cancer.

BACKGROUND: Colon cancer (CC) is a public health concern with increasing incidence in younger populations. Treatment for locally advanced CC (LACC) involves oncological surgery and adjuvant chemotherapy (AC) to reduce recurrence and improve overall survival (OS). Neoadjuvant chemotherapy (NAC) is a novel approach for the treatment of LACC, and research is underway to explore its potential benefit in terms of survival. This trial will assess the efficacy of NAC in LACC. METHODS: This is a multicentre randomised, parallel-group, open label controlled clinical trial. Participants will be selected based on homogenous inclusion criteria and randomly assigned to two treatment groups: NAC, surgery, and AC or surgery followed by AC. The primary aim of this study is to evaluate the 2-year progression-free survival (PFS), with secondary outcomes including 5-year PFS, 2- and 5-year OS, toxicity, radiological and pathological response, morbidity, and mortality. DISCUSSION: The results of this study will determine whether NAC induces a clinical and histological tumour response in patients with CCLA and if this treatment sequence improves survival without increasing morbidity and mortality. REGISTRATION NUMBER: NCT04188158.

Political Ideology Direction of Policy Agendas and Maternal Mortality Outcomes in the U.S., 1915-2007.

OBJECTIVES: The causes for persistently high and increasing maternal mortality rates in the United States have been elusive. METHODS: We use the shift in the ideological direction of the Republican and the Democratic parties in the 1960s, to test the hypothesis that fluctuations in overall and race-specific maternal mortality rates (MMR) follow the power shifts between the parties before and after the Political Realignment (PR) of the 1960s. RESULTS: Using time-series data analysis methods, we find that, net of trend, overall and race-specific MMRs were higher under Democratic administrations than Republican ones before the PR (1915-1965)-i.e., when the Democratic Party was a protector of the Jim Crow system. This pattern, however, changed after the PR (1966-2007), with Republican administrations underperforming Democratic ones-i.e., during the period when the Republican Party shifted toward a more economically and socially conservative agenda. The pre-post PR partisan shifts in MMRs were larger for Black (9.5%, p < . 01 ) relative to White mothers (7.4%, p < . 05 ) during the study period. CONCLUSIONS FOR PRACTICE: These findings imply that parties and the ideological direction of their agendas substantively affect the social determinants of maternal health and produce politized health outcomes.

Diagnosis and management of Abernethy syndrome.

Abernethy syndrome (AS or extrahepatic portosystemic shunt) is an uncommon congenital malformation consisting of agenesis or hypoplasia of the portal vein (PV) in such a way that splanchnic venous blood drains directly into the systemic circulation through aberrant communications, resulting in a portosystemic shunt that bypasses the liver AS is an underdiagnosed condition with unknown incidence and complication rate given that symptoms are usually absent. AS identification is increasingly common because of improved imaging techniques, hence prognostic implications and clinical management need be understood. This editorial reviews the natural history of AS and its diagnostic-therapeutic implications, illustrating the process with a series of cases from our institution.

Health care concerns in parents of children with different genetic developmental and epileptic encephalopathies: A qualitative study.

AIM: To describe the experiences and unmet medical care needs of a group of parents of children with developmental and epileptic encephalopathies (DEEs) caused by the SCN1A, KCNQ2, CDKL5, PCDH19, and GNAO1 variants. METHOD: A qualitative descriptive study was conducted. Participants were recruited using purposeful sampling. The inclusion criteria consisted of parents of children with DEEs caused by the SCN1A, KCNQ2, CDKL5, PCDH19, or GNAO1 variants, aged between 4 and 10 years old. In total, 21 parents were included. Data were acquired via researcher field notes and in-depth interviews. A thematic analysis was performed. RESULTS: Three main themes were identified: (1) managing symptoms: epileptic seizures are experienced with great uncertainty and are accompanied by cognitive, behavioural, and motor symptoms; (2) accepting treatment: the ideal medication regimen is a challenge and the decision to withdraw or start a new therapy falls on the parents; and (3) therapeutic relationship and medical care: behaviours related to the health professional can hinder the therapeutic relationship with the parents. Parents are apprehensive about going to the emergency department. INTERPRETATION: Professionals in emergency departments should acquire better knowledge of DEEs, welcome parents, and improve treatment for the children. The results of this study can serve as a starting point for a roadmap of relevant caregiver-reported outcomes in DEEs, to be implemented with new clinical trials and aetiology-targeted therapies. WHAT THIS PAPER ADDS: Epileptic seizures are the symptom that is most experienced and feared by parents. The medication regime has no defined protocol and the decision to withdraw a medication is frequently left to parents.

Antibiotic susceptibility and genotypic characterization of Neisseria gonorrhoeae isolates in the Comunidad Valenciana (Spain): GONOvig project.

INTRODUCTION: The increase in sexually transmitted infections (STI) caused by Neisseria gonorrhoeae (NG) worldwide, together with the decrease in antibiotic susceptibility, forced us to understand the epidemiology of gonococcal infection. METHODS: The GONOvig project analyzed, comparatively following CLSI and EUCAST criteria, the antibiotic susceptibility of 227 NG strains collected in thirteen representative hospitals of the Valencia Community (CV) between 2013 and 2018. Additionally, molecular typing of 175 strains using the NG multi-antigen sequence typing technique (NG-MAST) was performed. RESULTS: High rates of resistance to tetracycline (38.2% by CLSI and 50.9% by EUCAST) and ciprofloxacin (49.1% CLSI and 54% EUCAST), and low percentages of resistance to spectinomycin (0%), cefixime (0.5% CLSI but 5.9% EUCAST), and ceftriaxone (1.5% CLSI and 2.4% EUCAST) were detected. Azithromycin resistance was 6% (both CLSI and EUCAST). Molecular analysis revealed the presence of 86 different sequence types (ST), highlighting ST2992 (7.4%), ST3378 (6.9%), ST2400 (4.6%) and ST13288 (6.9%), which was associated with resistance to cefixime (P=.031). The main genogroups (G) were G1407 (13.1%), G2992 (10.3%), G2400 (6.3%) and G387 (3.4%). G1407 and G2400 were associated with resistance to ciprofloxacin (P<.03). CONCLUSION: Low resistance to ceftriaxone, a worrying resistance to azithromycin and a wide variety of circulating sequence types have been detected, some of which show correlation with certain resistance profiles.

Preocupaciones sobre la atención sanitaria en progenitores de niños con diferentes encefalopatías epilépticas genéticas del desarrollo: Un estudio cualitativo.

OBJETIVO: Describir las experiencias y las necesidades de atención médica de un grupo de progenitores de niños con encefalopatías epilépticas y del desarrollo (EED) causadas por las variantes SCN1A, KCNQ2, CDKL5, PCDH19 y GNAO1. MÉTODO: Se realizó un estudio cualitativo descriptivo. Los participantes fueron reclutados mediante un muestreo intencional. Los criterios de inclusión consistieron en progenitores de niños con EED causadas por las variantes SCN1A, KCNQ2, CDKL5, PCDH19 o GNAO1, con edades comprendidas entre los 4 y los 10 años. En total, se incluyeron 21 progenitores. Los datos se obtuvieron mediante entrevistas en profundidad y notas de campo del investigador. Se realizó un análisis temático. RESULTADOS: Se identificaron tres temas principales: (1) Manejando los síntomas, las crisis epilépticas se viven con gran incertidumbre, y se acompañan de síntomas cognitivos, conductuales y motores que limitan la vida del niño; b) Aceptando el tratamiento, la pauta de la medicación idónea es un reto, la decisión de retirar o comenzar una nueva terapia recae en los progenitores; y c) Relación terapéutica y atención médica, existen comportamientos y acciones del profesional que facilitan o dificultan la relación terapéutica con los progenitores. Acudir al servicio de urgencias es vivido con recelo por los progenitores. INTERPRETACIÓN: Los profesionales de los servicios de urgencias deben conocer mejor las EED, acoger a los progenitores y mejorar el tratamiento de los niños. Los resultados de este estudio pueden servir como punto de partida para una hoja de ruta de los resultados relevantes reportados por los cuidadores de las EED, a implementar nuevos ensayos clínicos y terapias dirigidas a la etiología. QUÉ AÑADE ESTE DOCUMENTO: Las crisis epilépticas son el síntomas más experimentado y temido por los progenitores en las EED. La pauta de la medicación no tiene un protocolo definido y la decisión de retirar una medicación recae en las manos de los progenitores.

Functional rehabilitation based on therapeutic exercise training in patients with postacute COVID syndrome (RECOVER).

INTRODUCTION AND OBJECTIVES: Postacute COVID syndrome (PACS) is common after acute SARS-CoV-2 infection. One of the most frequent and disabling symptoms is exercise intolerance (EI). Recent evidence suggests that EI in PACS has a peripheral (metabolic-neuromuscular) origin, suggesting that exercise training may be an effective treatment. The aim of this study was to assess the role a therapeutic physical exercise program (TPEP) in PACS with EI. METHODS: This single-center, open-label, randomized clinical trial compared an exercise training program (intervention group) with regular physical activity recommendations (control group) in patients with PACS and EI. The intervention group underwent an 8-week TPEP. The primary endpoint was improvement in functional capacity, assessed as the change in peak VO2. RESULTS: We included 50 participants with PACS (73% women, mean age 47±7.1 years). The intervention group showed a 15% improvement in peak VO2 (peak VO2 pre- and postintervention: 25.5±7.7mL/kg/min and 29.3±4.7 mL/kg/min; P <.001) and a 13.2% improvement in predicted values (92.1±14.3% and 108.4±13.4%; P <.001). No significant changes in VO2 values were observed in the control group. Unlike the control group, the intervention group also showed improvements in all secondary outcomes: quality of life scales, muscle power, maximum inspiratory power, metabolic flexibility, and body fat percentage. CONCLUSIONS: The program improved functional capacity in patients with PACS and EI.