Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review.

Community-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed.

Timing of intubation and ICU mortality in COVID-19 patients: a retrospective analysis of 4198 critically ill patients during the first and second waves.

BACKGROUND: The optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patients with acute respiratory failure (ARF). We hypothesized that delayed intubation is associated with a high risk of mortality in COVID-19 patients. METHODS: This is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021. Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, we excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis. RESULTS: We included 4,198 patients [median age, 63 (54‒71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3‒7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10‒18)], and median PaO2/FiO2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100‒190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7‒28) days. Mortality was higher in the "late group" than in the "early group" (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5‒0.7). CONCLUSIONS: Early intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality. TRIAL REGISTRATION: The study was registered at Clinical-Trials.gov (NCT04948242) (01/07/2021).

A reliable and valid tool to assess the sexual acceptability of contraceptive methods.

Introduction: Adequate identification of the sexual acceptability of contraceptive methods is key for designing health promotion interventions, assessing their impacts, and increasing their effectiveness. This study aimed to develop and validate a questionnaire to explore the preferences of women depending on their epidemiological characteristics and their partner relationships-the Sexual Acceptability of Contraceptive Methods Questionnaire [in Spanish, Aceptabilidad Sexual de los Métodos Anticonceptivos (ASMA)]. Methods: Psychometric validation was conducted using Exploratory Factorial Analysis (EFA) and confirmatory factor analysis (CFA). The reliability of the final version of the questionnaire was explored using Cronbach's alpha and McDonald omega to estimate internal consistency. Results: A three-factor model was identified. Factor 1 (explaining 28.32% of the model) corresponds to questions concerning the use and placement of the contraceptive and includes 6 items; Factor 2 (explaining 24.23%) corresponds to other factors that affect the relationship such as bleeding and side effects of the contraceptive method and includes 10 items; and Factor 3 (explaining 18.94%) corresponds to the couple relationship and includes 8 items. Conclusion and implications: The ASMA questionnaire provides a valid and reliable tool for assessing the sexual acceptability of various contraceptive methods. This instrument gathers data that provide information on various aspects of women's sexuality, health, education, and beliefs, all of which can determine the preference for one contraceptive method over another. Moreover, the tool can help to identify profiles of women who have different preferences when selecting a particular method.

Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients.

BACKGROUND: Procalcitonin (PCT) and C-Reactive Protein (CRP) are useful biomarkers to differentiate bacterial from viral or fungal infections, although the association between them and co-infection or mortality in COVID-19 remains unclear. METHODS: The study represents a retrospective cohort study of patients admitted for COVID-19 pneumonia to 84 ICUs from ten countries between (March 2020-January 2021). Primary outcome was to determine whether PCT or CRP at admission could predict community-acquired bacterial respiratory co-infection (BC) and its added clinical value by determining the best discriminating cut-off values. Secondary outcome was to investigate its association with mortality. To evaluate the main outcome, a binary logistic regression was performed. The area under the curve evaluated diagnostic performance for BC prediction. RESULTS: 4635 patients were included, 7.6% fulfilled BC diagnosis. PCT (0.25[IQR 0.1-0.7] versus 0.20[IQR 0.1-0.5]ng/mL, p<0.001) and CRP (14.8[IQR 8.2-23.8] versus 13.3 [7-21.7]mg/dL, p=0.01) were higher in BC group. Neither PCT nor CRP were independently associated with BC and both had a poor ability to predict BC (AUC for PCT 0.56, for CRP 0.54). Baseline values of PCT<0.3ng/mL, could be helpful to rule out BC (negative predictive value 91.1%) and PCT≥0.50ng/mL was associated with ICU mortality (OR 1.5,p<0.001). CONCLUSIONS: These biomarkers at ICU admission led to a poor ability to predict BC among patients with COVID-19 pneumonia. Baseline values of PCT<0.3ng/mL may be useful to rule out BC, providing clinicians a valuable tool to guide antibiotic stewardship and allowing the unjustified overuse of antibiotics observed during the pandemic, additionally PCT≥0.50ng/mL might predict worsening outcomes.

Mortality comparison between the first and second/third waves among 3,795 critical COVID-19 patients with pneumonia admitted to the ICU: A multicentre retrospective cohort study.

BACKGROUND: It is unclear whether the changes in critical care throughout the pandemic have improved the outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care units (ICUs). METHODS: We conducted a retrospective cohort study in adults with COVID-19 pneumonia admitted to 73 ICUs from Spain, Andorra and Ireland between February 2020 and March 2021. The first wave corresponded with the period from February 2020 to June 2020, whereas the second/third waves occurred from July 2020 to March 2021. The primary outcome was ICU mortality between study periods. Mortality predictors and differences in mortality between COVID-19 waves were identified using logistic regression. FINDINGS: As of March 2021, the participating ICUs had included 3795 COVID-19 pneumonia patients, 2479 (65·3%) and 1316 (34·7%) belonging to the first and second/third waves, respectively. Illness severity scores predicting mortality were lower in the second/third waves compared with the first wave according with the Acute Physiology and Chronic Health Evaluation system (median APACHE II score 12 [IQR 9-16] vs 14 [IQR 10-19]) and the organ failure assessment score (median SOFA 4 [3-6] vs 5 [3-7], p<0·001). The need of invasive mechanical ventilation was high (76·1%) during the whole study period. However, a significant increase in the use of high flow nasal cannula (48·7% vs 18·2%, p<0·001) was found in the second/third waves compared with the first surge. Significant changes on treatments prescribed were also observed, highlighting the remarkable increase on the use of corticosteroids to up to 95.9% in the second/third waves. A significant reduction on the use of tocilizumab was found during the study (first wave 28·9% vs second/third waves 6·2%, p<0·001), and a negligible administration of lopinavir/ritonavir, hydroxychloroquine, and interferon during the second/third waves compared with the first wave. Overall ICU mortality was 30·7% (n = 1166), without significant differences between study periods (first wave 31·7% vs second/third waves 28·8%, p = 0·06). No significant differences were found in ICU mortality between waves according to age subsets except for the subgroup of 61-75 years of age, in whom a reduced unadjusted ICU mortality was observed in the second/third waves (first 38·7% vs second/third 34·0%, p = 0·048). Non-survivors were older, with higher severity of the disease, had more comorbidities, and developed more complications. After adjusting for confounding factors through a multivariable analysis, no significant association was found between the COVID-19 waves and mortality (OR 0·81, 95% CI 0·64-1·03; p = 0·09). Ventilator-associated pneumonia rate increased significantly during the second/third waves and it was independently associated with ICU mortality (OR 1·48, 95% CI 1·19-1·85, p<0·001). Nevertheless, a significant reduction both in the ICU and hospital length of stay in survivors was observed during the second/third waves. INTERPRETATION: Despite substantial changes on supportive care and management, we did not find significant improvement on case-fatality rates among critical COVID-19 pneumonia patients. FUNDING: Ricardo Barri Casanovas Foundation (RBCF2020) and SEMICYUC.

Periodontal regeneration using a xenogeneic bone substitute seeded with autologous periodontal ligament-derived mesenchymal stem cells: A 12-month quasi-randomized controlled pilot clinical trial.

AIM: To evaluate the safety and efficacy of autologous periodontal ligament-derived mesenchymal stem cells (PDL-MSCs) embedded in a xenogeneic bone substitute (XBS) for the regenerative treatment of intra-bony periodontal defects. MATERIAL AND METHODS: This quasi-randomized controlled pilot phase II clinical trial included patients requiring a tooth extraction and presence of one intra-bony lesion (1-2 walls). Patients were allocated to either the experimental (XBS + 10 × 106 PDL-MSCs/100 mg) or the control group (XBS). Clinical and radiographical parameters were recorded at baseline, 6, 9 and 12 months. The presence of adverse events was also evaluated. Chi-square, Student's t test, Mann-Whitney U, repeated-measures ANOVA and regression models were used. RESULTS: Twenty patients were included. No serious adverse events were reported. Patients in the experimental group (n = 9) showed greater clinical attachment level (CAL) gain (1.44, standard deviation [SD] = 1.87) and probing pocket depth (PPD) reduction (2.33, SD = 1.32) than the control group (n = 10; CAL gain = 0.88, SD = 1.68, and PPD reduction = 2.10, SD = 2.46), without statistically significant differences. CONCLUSION: The application of PDL-MSCs to XBS for the treatment of one- to two-wall intra-bony lesions was safe and resulted in low postoperative morbidity and appropriate healing, although its additional benefit, when compared with the XBS alone, was not demonstrated.

A Randomized Controlled Trial to Examine the Posttreatment Efficacy of Neurofeedback, Behavior Therapy, and Pharmacology on ADHD Measures.

OBJECTIVE: To examine the efficacy of neurofeedback (NF), behavior therapy (BT), and pharmacology (PH) on the improvement of ADHD-related symptoms. METHOD: Fifty-nine children with ADHD ( M = 8.80 years, SD = 1.92 years) were randomly assigned to one of the three treatments in a pre/post assessment design. Mother- and teacher-rated ADHD scales and children were assessed using The Integrated Visual and Auditory Continuous Performance Test (IVA/CPT). RESULTS: The three treatments were effective on the IVA/CPT, but with different trends. BT and especially NF achieved improvement on response control and attention, and PH mainly in visual attention. On the rating scales, BT improved all measures, and NF and PH had a minor but interesting influence. CONCLUSION: From a global perspective, behavior therapy had the most extensive results, but PH had the greatest capacity to improve overall attention. NF was able to improve both control response and inattention. Clinical implications are discussed.

Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma.

We report the first evaluation of plant-made conjugate vaccines for targeted treatment of B-cell follicular lymphoma (FL) in a Phase I safety and immunogenicity clinical study. Each recombinant personalized immunogen consisted of a tumor-derived, plant-produced idiotypic antibody (Ab) hybrid comprising the hypervariable regions of the tumor-associated light and heavy Ab chains, genetically grafted onto a common human IgG1 scaffold. Each immunogen was produced in Nicotiana benthamiana plants using twin magnICON vectors expressing the light and heavy chains of the idiotypic Ab. Each purified Ab was chemically linked to the carrier protein keyhole limpet hemocyanin (KLH) to form a conjugate vaccine. The vaccines were administered to FL patients over a series of ≥6 subcutaneous injections in conjunction with the adjuvant Leukine (GM-CSF). The 27 patients enrolled in the study had previously received non-anti-CD20 cytoreductive therapy followed by ≥4 months of immune recovery prior to first vaccination. Of 11 patients who became evaluable at study conclusion, 82% (9/11) displayed a vaccine-induced, idiotype-specific cellular and/or humoral immune response. No patients showed serious adverse events (SAE) related to vaccination. The fully scalable plant-based manufacturing process yields safe and immunogenic personalized FL vaccines that can be produced within weeks of obtaining patient biopsies.

Role of atrial tissue remodeling on rotor dynamics: an in vitro study.

The objective of this article is to present an in vitro model of atrial cardiac tissue that could serve to study the mechanisms of remodeling related to atrial fibrillation (AF). We analyze the modification on gene expression and modifications on rotor dynamics following tissue remodeling. Atrial murine cells (HL-1 myocytes) were maintained in culture after the spontaneous initiation of AF and analyzed at two time points: 3.1 ± 1.3 and 9.7 ± 0.5 days after AF initiation. The degree of electrophysiological remodeling (i.e., relative gene expression of key ion channels) and structural inhomogeneity was compared between early and late cell culture times both in nonfibrillating and fibrillating cell cultures. In addition, the electrophysiological characteristics of in vitro fibrillation [e.g., density of phase singularities (PS/cm(2)), dominant frequency, and rotor meandering] analyzed by means of optical mapping were compared with the degree of electrophysiological remodeling. Fibrillating cell cultures showed a differential ion channel gene expression associated with atrial tissue remodeling (i.e., decreased SCN5A, CACN1C, KCND3, and GJA1 and increased KCNJ2) not present in nonfibrillating cell cultures. Also, fibrillatory complexity was increased in late- vs. early stage cultures (1.12 ± 0.14 vs. 0.43 ± 0.19 PS/cm(2), P < 0.01), which was associated with changes in the electrical reentrant patterns (i.e., decrease in rotor tip meandering and increase in wavefront curvature). HL-1 cells can reproduce AF features such as electrophysiological remodeling and an increased complexity of the electrophysiological behavior associated with the fibrillation time that resembles those occurring in patients with chronic AF.

Neurofeedback, pharmacological treatment and behavioral therapy in hyperactivity: Multilevel analysis of treatment effects on electroencephalography.

The purpose of this study was to investigate the efficacy of neurofeedback, pharmacological treatment and behavioral therapy in Attention Deficit Hyperactivity Disorder (ADHD) through a controlled, randomized, multigroup design, with pre-, post- and follow-up treatment phases. The objectives of this study are: a) to analyze individual trajectories over time of each child in treatment, from specific measures of EEG (theta/beta ratio/TBR) considering age and sex and b) to determine the therapeutic effect on attentional and behavioral variables evaluated through the Integrated Visual and Auditory Continuous Performance Test. A total of 57 children (7-14 years) diagnosed with ADHD, were randomly assigned to one of the following experimental conditions: 1) 30 Theta/Beta training sessions, 2) Methylphenidate treatment and, 3) Behavior therapy administered according to a cognitive-behavioral protocol based on manuals. Data were analyzed using a Multilevel Longitudinal Regression Model. Results show that administered treatments are effective and cause similar effects on TBR variable, with no differences between them. However, significant differences were observed in the global attention (p=.002), auditory attention (p=.017) and visual attention (p=.028).

Se investiga la eficacia del neurofeedback, tratamiento farmacológico y terapia de conducta en el Trastorno por Déficit de Atención con Hiperactividad (TDAH) mediante un diseño multigrupo, aleatorizado y controlado con fases pre, post-tratamiento y seguimiento. Se pretenden los siguientes objetivos: a) analizar las trayectorias individuales a través del tiempo, de cada niño en tratamiento, en la medida del EEG (theta/beta ratio/TBR), considerando edad y sexo, y b) determinar el efecto terapéutico en variables atencionales y conductuales evaluadas mediante el Integrated Visual and Auditory Continuous Performance Test. Participaron 57 niños (7-14 años) diagnosticados con TDAH, asignados aleatoriamente a alguna de las siguientes condiciones experimentales: 1) 30 sesiones de entrenamiento theta/beta, 2) tratamiento con metilfenidato y 3) terapia de conducta, según protocolo basado en manuales. Se ha empleado el Modelo Longitudinal de Regresión Multinivel para análisis de datos. Los resultados muestran que los tratamientos administrados son eficaces y originan efectos similares en la variable TBR, no apreciándose diferencias entre los mismos. Si bien, se observan diferencias significativas en la atención global (p=.002), atención auditiva (p=.017) y atención visual (p=.028).

Bone marrow mesenchymal stem cell aspirates from alternative sources: is the knee as good as the iliac crest?

INTRODUCTION: The most common method to obtain human mesenchymal stem cells (MSCs) is bone marrow aspiration from the iliac crest, but MSCs have also been isolated from different bones. The main purpose of this study was to compare bone marrow MSCs aspirated from the metaphysis of the distal femur and the proximal tibia with those obtained from the iliac crest, and to determine whether these locations represent potential alternative sources of MSCs for research and clinical application. MATERIALS AND METHODS: Bone marrow was aspirated from the iliac crest and the metaphysis of the distal femur and the proximal tibia during total knee arthroplasty in 20 patients. The aspirates were centrifuged by density gradient, then mononucleated cell (MNC) concentration in the different aspirates was determined using a Coulter counter. MSCs were isolated, cultivated and characterised by their immunophenotype and by their in vitro potential for differentiation into osteoblasts, chondroblasts and adipocytes in specific media. Expansion and cell viability were quantified using trypan blue staining and cell counting with a haemocytometer (Neubauer chamber). The three sources were compared in terms of MNC concentration, viability of the cultures and presence of MSC using the Wilcoxon test. RESULTS: MNC concentration was significantly higher in the iliac crest (10.05 Millions/ml) compared with the femur (0.67 Millions/ml) and tibia (1.7 Millions/ml). Culture success rates were 90%, 71% and 47% for MSCs from the iliac crest, femur and tibia, respectively. Flow cytometry analysis showed the presence of CD90+, CD105+, CD73+, VEGF+, CD71+, HLA-DR-, CD45-, CD34-, CD19-, and CD14- cells. The immunophenotype pattern of MSCs was similar for the three locations. Trilineage differentiation was achieved with all samples. CONCLUSIONS: MSCs can be found in bone marrow from the metaphysis of both the distal femur and the proximal tibia. The phenotype and differentiation potential of these cells are similar to those of bone marrow MSCs from the iliac crest. Bone marrow aspiration from these locations is a relatively easy and safe alternative to that from the iliac crest for obtaining MSCs. Further study is required to assess whether the concentrations of MSCs obtained from these sources are sufficient for one-step therapeutic purposes.

Prognostic factors of mortality in patients with community-acquired bloodstream infection with severe sepsis and septic shock.

PURPOSE: The purpose of the study was to determine the independent risk factors on mortality in patients with community-acquired severe sepsis and septic shock. METHODS: A single-site prospective cohort study was carried out in a medical-surgical intensive care unit in an academic tertiary care center. One hundred twelve patients with community-acquired bloodstream infection with severe sepsis and septic shock were identified. Clinical, microbiologic, and laboratory parameters were compared between hospital survivors and hospital deaths. RESULTS: One-hundred twelve patients were included. The global mortality rate was 41.9%, 44.5% in septic shock and 34.4% in severe sepsis. One or more comorbidities were present in 66% of patients. The most commonly identified bloodstream pathogens were Escherichia coli (25%) and Staphylococcus aureus (21.4%). The proportion of patients receiving inadequate antimicrobial treatment was 8.9%. By univariate analysis, age, Acute Physiology and Chronic Health Evaluation II score, at least 3 organ dysfunctions, and albumin, but neither microbiologic characteristics nor site of infection, differed significantly between survivors and nonsurvivors. Acute Physiology and Chronic Health Evaluation II (odds ratio, 1.13; 95% confidence interval, 1.06-1.21) and albumin (odds ratio, 0.34; 95% confidence interval, 0.15-0.76) were independent risk factors associated with global mortality in logistic regression analysis. CONCLUSION: In addition to the severity of illness, hypoalbuminemia was identified as the most important prognostic factor in community-acquired bloodstream infection with severe sepsis and septic shock.

[The euthyroid sick syndrome in severe acute illness]. / Syndrome de dyshormonémie euthyroïdienne au cours de la maladie aiguë grave.

OBJECTIVE: To describe euthyroid sick syndrome (ESS) and its different clinical variants in severe acute illness. DESIGN: This prospective cohort study examined hormone results and outcome for patients admitted to our intensive care unit (ICU). METHODS: In this heterogeneous group of 108 patients from our ICU we analyzed the prevalence of ESS and its influence on mortality and sought to determine if any thyroid indicators had a prognostic value. RESULTS: The prevalence of ESS was similar to that described by other authors (68.5% for ESS type I, 15.7% for type II and 1.9% for type III). Patients developed thyroid alterations on their third day of hospitalization and those with ESS type II had a higher mortality rate. The only thyroid indicator with prognostic value was a reverse triiodothyronine (rT3) value exceeding 0.61 ng/mL. CONCLUSION: Severe acute illness induced the thyroid alterations known as ESS. Type I had the highest prevalence, but type II was correlated with a higher mortality rate. The only thyroid indicator with a prognostic value was rT3.