A one-step method for generating antimicrobial nanofibre meshes via coaxial electrospinning.

Respiratory diseases, including influenza, infectious pneumonia, and severe acute respiratory syndrome (SARS), are a leading cause of morbidity and mortality worldwide. The recent COVID-19 pandemic claimed over 6.9 million lives globally. With the possibility of future pandemics, the creation of affordable antimicrobial meshes for protective gear, such as facemasks, is essential. Electrospinning has been a focus for much of this research, but most approaches are complex and expensive, often wasting raw materials by distributing antiviral agents throughout the mesh despite the fact they can only be active if at the fibre surface. Here, we report a low cost and efficient one-step method to produce nanofibre meshes with antimicrobial activity, including against SARS-CoV-2. Cetrimonium bromide (CTAB) was deposited directly onto the surface of polycaprolactone (PCL) fibres by coaxial electrospinning. The CTAB-coated samples have denser meshes with finer nanofibres than non-coated PCL fibres (mean diameter: ∼300 nm versus ∼900 nm, with mean pore size: ∼300 nm versus > 600 nm). The formulations have > 90% coating efficiency and exhibit a burst release of CTAB upon coming into contact with aqueous media. The CTAB-coated materials have strong antibacterial activity against Staphylococcus aureus (ca. 100%) and Pseudomonas aeruginosa (96.5 ± 4.1%) bacteria, as well as potent antiviral activity with over 99.9% efficacy against both respiratory syncytial virus and SARS-CoV-2. The CTAB-coated nanofibre mesh thus has great potential to form a mask material for preventing both bacterial and viral respiratory infections.

Main pulmonary artery diameter related to pneumonia severity.

The diameter (mPAD) of the main pulmonary artery (pulmonary artery trunk) is a crucial indicator for cardiovascular health and prognoses in various conditions. Its enlargement is associated with increased mortality and severity in COVID-19-related pneumonia. However, its relevance to non-COVID pneumonia remains uncertain. The aim of this study was to establish an association between mPAD and the severity of non-COVID pneumonia. Eligible participants with qualified Chest Computed Tomography scans from November 2019 to February 2023 were recruited to a cross-sectional retrospective study. They were stratified into pneumonia and non-pneumonia cohorts. Exclusion criteria included pulmonary hypertension, polytrauma, lung neoplasia, or a history of pulmonary stenosis repair. The mPAD was measured in both groups, and medical records were reviewed to identify comorbidities. Pulmonary CT data were classified by pattern and severity, and the mPAD was measured perpendicularly to the long axis of the artery at the point of bifurcation on an axial slice. Analysis of 380 CT scans (52.6% men, 47.4% women; mean age 52.88 ± 17.58) revealed a significant difference in mPAD between pneumonia and non-pneumonia cases (mean difference: 1.19 mm, 95% CI [0.46, 1.92], p = 0.001). Age correlated positively with mPAD (r = 0.231, 95% CI [0.028, 0.069], p < 0.0001), and this correlation persisted after adjusting for confounders (r = 0.220, 95% CI [0.019, 0.073], p = 0.001). Ordinal logistic regression indicated 1.28 times higher odds of severe pneumonia with a larger diameter. The study highlights associations between mPAD, pneumonia, and severity, suggesting clinical relevance. Furthermore, the mPAD should be carefully considered in defining severity criteria for adverse outcomes in pneumonia patients. Further research is needed to refine clinical criteria on the basis of these findings.

Comparative analysis of COVID-19-associated venous thromboembolism outcomes: evolution from 2020 to 2021-2022.

Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90 days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period.

Molecular circadian clock disruption in the leukocytes of individuals with type 2 diabetes and overweight, and its relationship with leukocyte-endothelial interactions.

AIMS/HYPOTHESIS: Alterations in circadian rhythms increase the likelihood of developing type 2 diabetes and CVD. Circadian rhythms are controlled by several core clock genes, which are expressed in nearly every cell, including immune cells. Immune cells are key players in the pathophysiology of type 2 diabetes, and participate in the atherosclerotic process that underlies cardiovascular risk in these patients. The role of the core clock in the leukocytes of people with type 2 diabetes and the inflammatory process associated with it are unknown. We aimed to evaluate whether the molecular clock system is impaired in the leukocytes of type 2 diabetes patients and to explore the mechanism by which this alteration leads to an increased cardiovascular risk in this population. METHODS: This is an observational cross-sectional study performed in 25 participants with type 2 diabetes and 28 healthy control participants. Clinical and biochemical parameters were obtained. Peripheral blood leukocytes were isolated using magnetic bead technology. RNA and protein lysates were obtained to assess clock-related gene transcript and protein levels using real-time PCR and western blot, respectively. Luminex XMAP technology was used to assess levels of inflammatory markers. Leukocyte-endothelial interaction assays were performed by perfusing participants' leukocytes or THP-1 cells (with/without CLK8) over a HUVEC monolayer in a parallel flow chamber using a dynamic adhesion system. RESULTS: Participants with type 2 diabetes showed increased BMAL1 and NR1D1 mRNA levels and decreased protein levels of circadian locomotor output cycles kaput (CLOCK), cryptochrome 1 (CRY1), phosphorylated basic helix-loop-helix ARNT like 1 (p-BMAL1) and period circadian protein homologue 2 (PER2). Correlation studies revealed that these alterations in clock proteins were negatively associated with glucose, HbA1c, insulin and HOMA-IR levels and leukocyte cell counts. The leukocyte rolling velocity was reduced and rolling flux and adhesion were enhanced in individuals with type 2 diabetes compared with healthy participants. Interestingly, inhibition of CLOCK/BMAL1 activity in leukocytes using the CLOCK inhibitor CLK8 mimicked the effects of type 2 diabetes on leukocyte-endothelial interactions. CONCLUSIONS/INTERPRETATION: Our study demonstrates alterations in the molecular clock system in leukocytes of individuals with type 2 diabetes, manifested in increased mRNA levels and decreased protein levels of the core clock machinery. These alterations correlated with the impaired metabolic and proinflammatory profile of the participants with type 2 diabetes. Our findings support a causal role for decreased CLOCK/BMAL1 activity in the increased level of leukocyte-endothelial interactions. Overall, our data suggest that alterations in core clock proteins accelerate the inflammatory process, which may ultimately precipitate the onset of CVD in patients with type 2 diabetes.

Middle ear morphology and mastoid pneumatization: a computed tomography study.

BACKGROUND: Mastoid pneumatization is subject to numerous influencing factors including race, sex, and surrounding structures of the middle ear. This study aims to determine the mastoid air cell system (MACS) volume and its relationship with middle ear structures, and the influence of sex. MATERIALS AND METHODS: A cross-sectional study was performed analyzing computed tomography (CT) scans in which MACS volume and the Estachian tube length (ETL) were visible. MACS volume, ETL, and width and height of the aditus ad antrum were obtained. RESULTS: A total of 100 CT were included with a mean age of 38.5 ± 15.3 years, of which 56 were women and 44 were men. The mean right and left MACS volume were 5.43 ± 3.15 cm³ and 5.54 ± 3.43 cm3 respectively , with a ETL of 24.55 ± 3.07 mm in right side and 24.24 ± 2.60 mm on left side. A aditus ad antrum width of 2.98 ± 0.65 in right and 2.98 ± 0.58 on the left and height of 4.51 ± 1.05 and 4.32 ± 0.85, on right and left side respectively. There were statistical differences between sexes in left ETL, and in MACS volume bilaterally. A low positive correlation between aditus ad antrum height and MACS volume was identified. CONCLUSIONS: Mastoid pneumatization was bigger in men than women. There was a low positive correlation between mastoid volume and ETL on both sides, and a significant correlation between right mastoid volume and aditus ad antrum height. This could lead us to believe that the length of ETL does not affect the pneumatization of MACS.

Temporal trends on the prevalence of renal disease and outcomes among patients with diabetes mellitus hospitalized by heart failure: findings from INCAex.

BACKGROUND: To assess 20-year time trends in the prevalence of diabetes mellitus (DM) among inpatients with heart failure (HF) and the influence of coexisting DM and kidney disease (KD) on outcomes. RESEARCH DESIGN AND METHODS: A retrospective study of patients was admitted due to HF, during the period 2000/2019. The period of follow-up was divided into three intervals according to the European Medical Agency approval of newer hypoglycemic drugs. We analyzed in-hospital mortality and outcomes during the follow-up period. RESULTS: A total of 4959 patients were included. Over time, prevalence of DM was significantly raising among women with HF (50 to 53.2%) and descending among men (50% to 46.8%, p = 0.02). Total mortality and readmissions were higher in patients with DM during the and second periods. However, no significant differences were found in the third-one (HR 1.14, 95% CI 0.94-1.39, p = 0.181). A protector role of oral hypoglycemic medications was observed in this last period. According to the presence of KD, the patients with both DM and KD were who presented most of the events. CONCLUSIONS: Over the time analyzed, the prevalence of DM raised among women and decreased among men. DM influenced the prognosis of HF except in the third period when more protective hypoglycemic drugs started to be used.

Leveraging deep learning for detecting red blood cell morphological changes in blood films from children with severe malaria anaemia.

In sub-Saharan Africa, acute-onset severe malaria anaemia (SMA) is a critical challenge, particularly affecting children under five. The acute drop in haematocrit in SMA is thought to be driven by an increased phagocytotic pathological process in the spleen, leading to the presence of distinct red blood cells (RBCs) with altered morphological characteristics. We hypothesized that these RBCs could be detected systematically and at scale in peripheral blood films (PBFs) by harnessing the capabilities of deep learning models. Assessment of PBFs by a microscopist does not scale for this task and is subject to variability. Here we introduce a deep learning model, leveraging a weakly supervised Multiple Instance Learning framework, to Identify SMA (MILISMA) through the presence of morphologically changed RBCs. MILISMA achieved a classification accuracy of 83% (receiver operating characteristic area under the curve [AUC] of 87%; precision-recall AUC of 76%). More importantly, MILISMA's capabilities extend to identifying statistically significant morphological distinctions (p < 0.01) in RBCs descriptors. Our findings are enriched by visual analyses, which underscore the unique morphological features of SMA-affected RBCs when compared to non-SMA cells. This model aided detection and characterization of RBC alterations could enhance the understanding of SMA's pathology and refine SMA diagnostic and prognostic evaluation processes at scale.

The prognostic value of blood cellular indices in pulmonary embolism.

Prognostication in acute pulmonary embolism (PE) requires reliable markers. While cellular indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) appear promising, their utility in PE prognostication needs further exploration. We utilized data from the RIETE registry and the Loyola University Medical Center (LUMC) to assess the prognostic value of NLR, PLR, and SII in acute PE, using logistic regression models. The primary outcome was 30-day all-cause mortality. We compared their prognostic value versus the simplified Pulmonary Embolism Severity Index (sPESI) alone. We included 10 085 patients from RIETE and 700 from the LUMC. Thirty-day mortality rates were 4.6% and 8.3%, respectively. On multivariable analysis, an elevated NLR (>7.0) was associated with increased mortality (adjusted odds ratio [aOR]: 3.46; 95% CI: 2.60-4.60), outperforming the PLR > 220 (aOR: 2.36; 95% CI: 1.77-3.13), and SII > 1600 (aOR: 2.52; 95% CI: 1.90-3.33). The c-statistic for NLR in patients with low-risk PE was 0.78 (95% CI: 0.69-0.86). Respective numbers were 0.66 (95% CI: 0.63-0.69) and 0.68 (95% CI: 0.59-0.76) for intermediate-risk and high-risk patients. These findings were mirrored in the LUMC cohort. Among 9810 normotensive patients in RIETE, those scoring 0 points in sPESI and with an NLR ≤ 7.0 (35% of the population) displayed superior sensitivity (97.1%; 95% CI: 95.5-98.7) and negative predictive value (99.7%; 95% CI: 99.5-99.8) than sPESI alone (87.1%; 95% CI: 83.9-90.3, and 98.7%; 95% CI: 98.4-99.1, respectively) for 30-day mortality. The NLR is a significant prognostic marker for 30-day mortality in PE patients, especially useful to identify patients with very low-risk PE.

Specialist hybrid models with asymmetric training for malaria prevalence prediction.

Malaria is a common and serious disease that primarily affects developing countries and its spread is influenced by a variety of environmental and human behavioral factors; therefore, accurate prevalence prediction has been identified as a critical component of the Global Technical Strategy for Malaria from 2016 to 2030. While traditional differential equation models can perform basic forecasting, supervised machine learning algorithms provide more accurate predictions, as demonstrated by a recent study using an elastic net model (REMPS). Nevertheless, current short-term prediction systems do not achieve the required accuracy levels for routine clinical practice. To improve in this direction, stacked hybrid models have been proposed, in which the outputs of several machine learning models are aggregated by using a meta-learner predictive model. In this paper, we propose an alternative specialist hybrid approach that combines a linear predictive model that specializes in the linear component of the malaria prevalence signal and a recurrent neural network predictive model that specializes in the non-linear residuals of the linear prediction, trained with a novel asymmetric loss. Our findings show that the specialist hybrid approach outperforms the current state-of-the-art stacked models on an open-source dataset containing 22 years of malaria prevalence data from the city of Ibadan in southwest Nigeria. The specialist hybrid approach is a promising alternative to current prediction methods, as well as a tool to improve decision-making and resource allocation for malaria control in high-risk countries.

Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes.

OBJECTIVE: Type 2 diabetes (T2D) is linked to metabolic, mitochondrial and inflammatory alterations, atherosclerosis development and cardiovascular diseases (CVDs). The aim was to investigate the potential therapeutic benefits of GLP-1 receptor agonists (GLP-1 RA) on oxidative stress, mitochondrial respiration, leukocyte-endothelial interactions, inflammation and carotid intima-media thickness (CIMT) in T2D patients. RESEARCH DESIGN AND METHODS: Type 2 diabetic patients (255) and control subjects (175) were recruited, paired by age and sex, and separated into two groups: without GLP-1 RA treatment (196) and treated with GLP-1 RA (59). Peripheral blood polymorphonuclear leukocytes (PMNs) were isolated to measure reactive oxygen species (ROS) production by flow cytometry and oxygen consumption with a Clark electrode. PMNs were also used to assess leukocyte-endothelial interactions. Circulating levels of adhesion molecules and inflammatory markers were quantified by Luminex's technology, and CIMT was measured as surrogate marker of atherosclerosis. RESULTS: Treatment with GLP-1 RA reduced ROS production and recovered mitochondrial membrane potential, oxygen consumption and MPO levels. The velocity of leukocytes rolling over endothelial cells increased in PMNs from GLP-1 RA-treated patients, whereas rolling and adhesion were diminished. ICAM-1, VCAM-1, IL-6, TNFα and IL-12 protein levels also decreased in the GLP-1 RA-treated group, while IL-10 increased. CIMT was lower in GLP-1 RA-treated T2D patients than in T2D patients without GLP-1 RA treatment. CONCLUSIONS: GLP-1 RA treatment improves the redox state and mitochondrial respiration, and reduces leukocyte-endothelial interactions, inflammation and CIMT in T2D patients, thereby potentially diminishing the risk of atherosclerosis and CVDs.

Effect of Immunosuppressive Treatments on Kidney Outcomes After Gross Hematuria-Related Acute Kidney Injury in Older Patients With IgA Nephropathy.

Introduction: Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the elderly. Immunosuppressive therapies are used in clinical practice; however, no studies have analyzed their efficacy on kidney outcomes. Methods: This is a retrospective, multicenter study of a cohort of patients aged ≥50 years with biopsy-proven IgAN presenting with AKI-MH. Outcomes were complete, partial, or no recovery of kidney function at 1 year after AKI-MH, and kidney survival at 1, 2, and 5 years. Propensity score matching (PSM) analysis was applied to balance baseline differences between patients treated with immunosuppression and those not treated with immunosuppression. Results: The study group consisted of 91 patients with a mean age of 65 ± 15 years, with a mean follow-up of 59 ± 36 months. Intratubular red blood cell (RBC) casts and acute tubular necrosis were found in all kidney biopsies. The frequency of endocapillary hypercellularity and crescents were low. Immunosuppressive therapies (corticosteroids alone or combined with mycophenolate mofetil or cyclophosphamide) were prescribed in 52 (57%) patients, whereas 39 (43%) received conservative treatment. There were no significant differences in the proportion of patients with complete, partial, or no recovery of kidney function at 1 year between patients treated with immunosuppression and those not treated with immunosuppression (29% vs. 36%, 30.8% vs. 20.5% and 40.4 % vs. 43.6%, respectively). Kidney survival at 1, 3, and 5 years was similar among treated and untreated patients (85% vs. 81%, 77% vs. 76% and 72% vs. 66%, respectively). Despite the PSM analysis, no significant differences were observed in kidney survival between the two groups. Fourteen patients (27%) treated with immunosuppression had serious adverse events. Conclusions: Immunosuppressive treatments do not modify the unfavorable prognosis of patients with IgAN who are aged ≥50 years presenting with AKI-MH, and are frequently associated with severe complications.

Portal hypertension hemorrhage secondary to a stomal varicose vein in a patient with two consecutive thrombosis of a transjugular intrahepatic portosystemic shunt (TIPS).

Less than 5% of patients with liver cirrhosis (LC) with portal hypertension (PH) develop atypical shunt (in regions other than the esophagus or the stomach). Within this group are varices associated with a stoma, for example the ones associated with an uretero-ileostomy which are infrequent. They are a diagnostic and therapeutic challenge, as they can cause hemorrhages due to PH. We present a clinical case about stoma varicose bleeding as the latest guidelines for the management of PH do not mention them or their treatment due to their low incidence.

Lung ultrasound score severity cut-off points in COVID-19 pneumonia. A systematic review and validating cohort.

Objectives: Our purpose was to establish different cut-off points based on the lung ultrasound score (LUS) to classify COVID-19 pneumonia severity. Methods: Initially, we conducted a systematic review among previously proposed LUS cut-off points. Then, these results were validated by a single-centre prospective cohort study of adult patients with confirmed SARS-CoV-2 infection. Studied variables were poor outcome (ventilation support, intensive care unit admission or 28-days mortality) and 28-days mortality. Results: From 510 articles, 11 articles were included. Among the cut-off points proposed in the articles included, only the LUS > 15 cut-off point could be validated for its original endpoint, demonstrating also the strongest relation with poor outcome (odds ratio [OR] = 3.636, confidence interval [CI] 1.411-9.374). Regarding our cohort, 127 patients were admitted. In these patients, LUS was statistically associated with poor outcome (OR = 1.303, CI 1.137-1.493), and with 28-days mortality (OR = 1.024, CI 1.006-1.042). LUS > 15 showed the best diagnostic performance when choosing a single cut-off point in our cohort (area under the curve 0.650). LUS ≤ 7 showed high sensitivity to rule out poor outcome (0.89, CI 0.695-0.955), while LUS > 20 revealed high specificity to predict poor outcome (0.86, CI 0.776-0.917). Conclusions: LUS is a good predictor of poor outcome and 28-days mortality in COVID-19. LUS ≤ 7 cut-off point is associated with mild pneumonia, LUS 8-20 with moderate pneumonia and ≥20 with severe pneumonia. If a single cut-off point were used, LUS > 15 would be the point which better discriminates mild from severe disease.

Objetivos: Establecer diferentes puntos de corte basados en el Lung Ultrasound Score (LUS) para clasificar la gravedad de la neumonía COVID-19. Métodos: Inicialmente, realizamos una revisión sistemática entre los puntos de corte LUS propuestos previamente. Estos resultados fueron validados por una cohorte prospectiva unicéntrica de pacientes adultos con infección confirmada por SARS-CoV-2. Las variables analizadas fueron la mala evolución y la mortalidad a los 28 días. Resultados: De 510 artículos, se incluyeron 11. Entre los puntos de corte propuestos en los artículos incluidos, solo LUS > 15 pudo ser validado para su objetivo original, demostrando también la relación más fuerte con mala evolución (odds ratio [OR] = 3,636, intervalo de confianza [IC] 1,411-9,374). Respecto a nuestra cohorte, se incluyeron 127 pacientes. En estos pacientes, el LUS se asoció estadísticamente con mala evolución (OR = 1,303, IC 1,137-1,493) y con mortalidad a los 28 días (OR = 1,024, IC 1,006-1,042). LUS > 15 mostró el mejor rendimiento diagnóstico al elegir un único punto de corte en nuestra cohorte (área bajo la curva 0,650). LUS ≤ 7 mostró una alta sensibilidad para descartar mal resultado (0,89, IC 0,695-0,955), mientras que LUS > 20 reveló gran especificidad para predecir mala evolución (0,86, IC 0,776-0,917). Conclusiones: LUS es un buen predictor de mala evolución y mortalidad a 28 días en COVID-19. LUS ≤ 7 se asocia con neumonía leve, LUS 8-20 con neumonía moderada y ≥ 20 con neumonía grave. Si se utilizara un único punto de corte, LUS > 15 sería el que mejor discriminaría la enfermedad leve de la grave.

Low-field magnetic resonance image enhancement via stochastic image quality transfer.

Low-field (<1T) magnetic resonance imaging (MRI) scanners remain in widespread use in low- and middle-income countries (LMICs) and are commonly used for some applications in higher income countries e.g. for small child patients with obesity, claustrophobia, implants, or tattoos. However, low-field MR images commonly have lower resolution and poorer contrast than images from high field (1.5T, 3T, and above). Here, we present Image Quality Transfer (IQT) to enhance low-field structural MRI by estimating from a low-field image the image we would have obtained from the same subject at high field. Our approach uses (i) a stochastic low-field image simulator as the forward model to capture uncertainty and variation in the contrast of low-field images corresponding to a particular high-field image, and (ii) an anisotropic U-Net variant specifically designed for the IQT inverse problem. We evaluate the proposed algorithm both in simulation and using multi-contrast (T1-weighted, T2-weighted, and fluid attenuated inversion recovery (FLAIR)) clinical low-field MRI data from an LMIC hospital. We show the efficacy of IQT in improving contrast and resolution of low-field MR images. We demonstrate that IQT-enhanced images have potential for enhancing visualisation of anatomical structures and pathological lesions of clinical relevance from the perspective of radiologists. IQT is proved to have capability of boosting the diagnostic value of low-field MRI, especially in low-resource settings.

Comparison of three fluids for calibration of the new Periotron® 8010.

BACKGROUND: The aim of the present study was to calibrate the Periotron® model 8010 with volumes of three different fluids (distilled water, serum, and saliva) and to identify which of the three is the most reliable, feasible, and reproducible for routine calibration. MATERIAL AND METHODS: A total of 450 samples of Periopaper® were divided into three groups (150 each per group): distilled water, serum matrix and saliva. A calibration curve was run with 0.25, 0.50, 0.75, 1.00 and 1.25 µl of each of the fluids, and the results were determined in Periotron units (PU). Statistical analysis was performed with one-way ANOVA followed by Bonferroni's post hoc test and a linear equation. RESULTS: Distilled water presented the lowest levels of PU at all volumes, while serum showed the highest levels at high volumes. Linear regression equations rendered similar slopes for saliva and distilled water, while serum was statistically different. Saliva presented a reproduction percentage of 99.7%, which indicated better accuracy and precision than serum and distilled water. CONCLUSIONS: Saliva is more reliable and accurate than water or serum for the purpose of calibration of the Periotron® model 8010, though it shares drawbacks with serum. Distilled water is more easily available and does not require any additional procedure, in addition to producing a similar slope to saliva and a smaller deviation from the media than serum.

Characteristics and clinical outcome in 312 patients with moderate to severe pneumonia due to SARS-COV-2 and hyperinflammation treated with anakinra and corticosteroids: A retrospective cohort study.

OBJECTIVE: To assess the clinical outcome (death and/or Intensive Care Unit (ICU) admission) based on the time from hospital admission to the administration of anakinra and the possible usefulness of a "simplified" SCOPE score to stratify the risk of worse prognosis in our cohort of patients with moderate/severe SARS-CoV-2 pneumonia, both vaccinated and unvaccinated, that received anakinra and corticosteroids. In addition, the clinical, analytical, and imaging characteristics of patients at admission are described. METHODS: Retrospective cohort study of 312 patients admitted to Hospital Clínico San Cecilio in Granada for moderate/severe pneumonia caused by SARS-CoV-2 that received anakinra and corticosteroids between March 2020 and January 2022. Clinical and analytical data were collected as well as the patient outcome at 30 and 60 days after admission. Three treatment groups were established according to the time from hospital admission to administration of anakinra: early (1st-2nd day), intermediate (3rd-5th day), and late (after the 5th day). RESULTS: The median age was 67.4 years (IQR 22-97 years) and 204 (65.4%) were male. The most common comorbidity was hypertension (58%). The median time from the start of symptoms to anakinra administration was 6 days (IQR 5-10) and the SaFi (SaO2/FiO2) was 228 (IQR 71-471). The cure rate was higher in the early-onset anakinra group versus the late-onset group (73% vs 56.6%). The latter had a higher percentage of deaths (27.4%) and a greater number of patients remained hospitalized for a month (16%). On admission, the patients had elevated C-reactive protein (CRP), ferritin, and D-dimer values and decreased total lymphocytes. Analytical improvement was observed at both 72 hours and one month after treatment. 42 (13.5%) required ICU admission, and 23 (7.3%) orotracheal intubation. At 60 days, 221 (70.8%) were discharged, 87 (27.8%) had died and 4 (1.4%) remained hospitalized. The mean dose of anakinra was 1000 mg (100-2600 mg) with differences found between the dose administered and the clinical outcome. There were no differences in the primary outcome based on vaccination. A simplified SCOPE score at the start of anakinra administration was lower in patients with better clinical evolution. CONCLUSIONS: Early treatment with anakinra and corticosteroids was associated with a better outcome regardless of vaccination status. A simplified SCOPE was found to be a good prognostic tool.

Lung ultrasound score severity cut-off points in COVID-19 pneumonia. A systematic review and validating cohort.

OBJECTIVES: Our purpose was to establish different cut-off points based on the lung ultrasound score (LUS) to classify COVID-19 pneumonia severity. METHODS: Initially, we conducted a systematic review among previously proposed LUS cut-off points. Then, these results were validated by a single-centre prospective cohort study of adult patients with confirmed SARS-CoV-2 infection. Studied variables were poor outcome (ventilation support, intensive care unit admission or 28-days mortality) and 28-days mortality. RESULTS: From 510 articles, 11 articles were included. Among the cut-off points proposed in the articles included, only the LUS>15 cut-off point could be validated for its original endpoint, demonstrating also the strongest relation with poor outcome (odds ratio [OR]=3.636, confidence interval [CI] 1.411-9.374). Regarding our cohort, 127 patients were admitted. In these patients, LUS was statistically associated with poor outcome (OR=1.303, CI 1.137-1.493), and with 28-days mortality (OR=1.024, CI 1.006-1.042). LUS>15 showed the best diagnostic performance when choosing a single cut-off point in our cohort (area under the curve 0.650). LUS≤7 showed high sensitivity to rule out poor outcome (0.89, CI 0.695-0.955), while LUS>20 revealed high specificity to predict poor outcome (0.86, CI 0.776-0.917). CONCLUSIONS: LUS is a good predictor of poor outcome and 28-days mortality in COVID-19. LUS≤7 cut-off point is associated with mild pneumonia, LUS 8-20 with moderate pneumonia and ≥20 with severe pneumonia. If a single cut-off point were used, LUS>15 would be the point which better discriminates mild from severe disease.

Prevalence, Risk Factors and Impact of Nutrition Interruptions in Critically Ill Children.

Background: Enteral nutrition interruptions (ENI) are prevalent in the pediatric intensive care unit (PICU), but there is little evidence of their characteristics. Methods: This is a cross-sectional multicenter study including critically ill children on enteral nutrition. ENIs were classified as PICU procedures, procedures performed outside the PICU (PPOP), feeding intolerance and other criteria. The number and features of ENIs were collected. Results: A total of 75 children were enrolled. There were 41 interruptions affecting 37.3% of the patients with a median duration of 5 ± 9.4 h. The most common reason for ENI was PPOP (41.5%), followed by other criteria. Interruptions were considered preventable in 24.4% of the cases, but only eight were compensated. ENIs were more prevalent among children with cardiac disease (p = 0.047), higher PRISM (p = 0.047) and longer PICU stay (p = 0.035). There was association between PRISM and total interruption time (p = 0.02) and lower caloric intake (p = 0.035). Patients with respiratory illness (p = 0.022) and on noninvasive ventilation (p = 0,028) had fewer ENIs. ENI total time was associated with lower caloric (p = 0.001) and protein (p = 0.02) intake. Conclusions: ENIs are prevalent in PICU, especially in children with higher PRISM, longer PICU stays and cardiac disease, and result in lower caloric and protein intake.