Safety of a controlled human infection model of tuberculosis with aerosolised, live-attenuated Mycobacterium bovis BCG versus intradermal BCG in BCG-naive adults in the UK: a dose-escalation, randomised, controlled, phase 1 trial.

BACKGROUND: Mycobacterium tuberculosis is the main causative agent of tuberculosis. BCG, the only licensed vaccine, provides inadequate protection against pulmonary tuberculosis. Controlled human infection models are useful tools for vaccine development. We aimed to determine a safe dose of aerosol-inhaled live-attenuated Mycobacterium bovis BCG as a surrogate for M tuberculosis infection, then compare the safety and tolerability of infection models established using aerosol-inhaled and intradermally administered BCG. METHODS: This phase 1 controlled human infection trial was conducted at two clinical research facilities in the UK. Healthy, immunocompetent adults aged 18-50 years, who were both M tuberculosis-naive and BCG-naive and had no history of asthma or other respiratory diseases, were eligible for the trial. Participants were initially enrolled into group 1 (receiving the BCG Danish strain); the trial was subsequently paused because of a worldwide shortage of BCG Danish and, after protocol amendment, was restarted using the BCG Bulgaria strain (group 2). After a dose-escalation study, during which participants were sequentially allocated to receive either 1 × 103, 1 × 104, 1 × 105, 1 × 106, or 1 × 107 colony-forming units (CFU) of aerosol BCG, the maximum tolerated dose was selected for the randomised controlled trial. Participants in this trial were randomly assigned (9:12), by variable block randomisation and using sequentially numbered sealed envelopes, to receive aerosol BCG (1 × 107 CFU) and intradermal saline or intradermal BCG (1 × 106 CFU) and aerosol saline. Participants were masked to treatment allocation until day 14. The primary outcome was to compare the safety of a controlled human infection model based on aerosol-inhaled BCG versus one based on intradermally administered BCG, and the secondary outcome was to evaluate BCG recovery in the airways of participants who received aerosol BCG or skin biopsies of participants who received intradermal BCG. BCG was detected by culture and by PCR. The trial is registered at ClinicalTrials.gov, NCT02709278, and is complete. FINDINGS: Participants were assessed for eligibility between April 7, 2016, and Sept 29, 2018. For group 1, 15 participants were screened, of whom 13 were enrolled and ten completed the study; for group 2, 60 were screened and 33 enrolled, all of whom completed the study. Doses up to 1 × 107 CFU aerosol-inhaled BCG were sufficiently well tolerated. No significant difference was observed in the frequency of adverse events between aerosol and intradermal groups (median percentage of solicited adverse events per participant, post-aerosol vs post-intradermal BCG: systemic 7% [IQR 2-11] vs 4% [1-13], p=0·62; respiratory 7% [1-19] vs 4% [1-9], p=0·56). More severe systemic adverse events occurred in the 2 weeks after aerosol BCG (15 [12%] of 122 reported systemic adverse events) than after intradermal BCG (one [1%] of 94; difference 11% [95% CI 5-17]; p=0·0013), but no difference was observed in the severity of respiratory adverse events (two [1%] of 144 vs zero [0%] of 97; 1% [-1 to 3]; p=0·52). All adverse events after aerosol BCG resolved spontaneously. One serious adverse event was reported-a participant in group 2 was admitted to hospital to receive analgesia for a pre-existing ovarian cyst, which was deemed unrelated to BCG infection. On day 14, BCG was cultured from bronchoalveolar lavage samples after aerosol infection and from skin biopsy samples after intradermal infection. INTERPRETATION: This first-in-human aerosol BCG controlled human infection model was sufficiently well tolerated. Further work will evaluate the utility of this model in assessing vaccine efficacy and identifying potential correlates of protection. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, Thames Valley Clinical Research Network, and TBVAC2020.

Primary Management of Operable Locally Advanced Oral Cavity Squamous Cell Carcinoma: Current Concepts and Strategies.

INTRODUCTION: Locally advanced oral cavity carcinoma (LAOCSCC) is primarily treated with surgery followed by radiotherapy with or without chemotherapy. METHODS: A review of literature using PubMED was performed for studies reporting the management of LAOCSCC. Based on the reviewed literature and opinions of experts in the field, recommendations were made. RESULTS: Studies have shown that outcomes following resection of T4a and infranotch (inferior to mandibular notch) T4b are comparable. We discuss the concept of compartmental resection of LAOCSCC and issues concerning the management of the neck. Further, patients who refuse or are unable to undergo surgery can be treated with chemoradiotherapy with uncertain outcomes. The role of neoadjuvant chemotherapy has shown promise for organ (mandibular) preservation in a select subset of patients. CONCLUSION: The management strategy for LAOCSCC should be determined in a multidisciplinary setting with emphasis on tumor control, functional preservation, and quality of life of the patient.

Molecularly defined sinonasal malignancies: an overview with focus on the current WHO classification and recently described provisional entities.

Classification of tumors of the head and neck has evolved in recent decades including a widespread application of molecular testing in tumors of the sinonasal tract, salivary glands, and soft tissues with a predilection for the head and neck. The availability of new molecular techniques has allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, an expanding spectrum of immunohistochemical markers specific to genetic alterations facilitates rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined tumor classification while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review covers the principal molecular alterations in sinonasal malignancies, such as alterations in DEK, AFF2, NUTM1, IDH1-2, and SWI/SNF genes in particular, that are important from a practical standpoint for diagnosis, prognosis, and prediction of response to treatment.

Prospective study of maturation and injury in elite handball academy. Could ‘maturational status’ be a risk factor for injury incidence in different handball team categories?

The objective of this study is to describe the relationship between injury incidence (IL) and maturity in male elite handball's player (HbP). Prospective study during two seasons, evaluating the sports injuries, maturity status and exposure time in hours in 133 young handball's players, under the UEFA methodology model for epidemiological studies. We discuss the maturity stage with different parameters, the Tanner's stage, puberty stages, peak high velocity, testicular volume, and the bone age. Finally, 190 injuries for a total of 34.222 h of exposure were registered. The average total Injury Incidence (IIn) by categories was 5,6 injury/1000 h of exposure. Injury Incidence during competition: 21,8 injuries/1000 hs and in training: 3,1 injuries/1000 hs without statistically significant between IIn, chronological age and different maturity stage by ANOVA. The multivariate statistical analysis registers tendency associations between IIn in competition for category (P = 0,07), and the IIn in training for Tanner stage (P = 0,091) and puberty (P = 0,021). In conclusion: there is not a significant difference in total IIn by ages categories in handball players but there is statistically significance tendency respect to some maturity parameters under a multivariate analysis. This last result must be considered when planning training seasons and strategies for injury prevention in the context of the formative handball. (AU)

Self-perception of mental health, COVID-19 and associated sociodemographic-contextual factors in Latin America.

This study aimed to estimate the prevalence of alterations in self-perceived mental health during the COVID-19 pandemic and their associated factors in four Latin American countries. This is a cross-sectional study based on data collected from adults in 2021 through the Collaborative Response COVID-19 Survey by the MacDonnell Academy at Washington University in St. Louis (United States). The sample was composed of 8,125 individuals from Brazil, Colombia, Mexico, and Chile. A generalized linear model for a binary outcome variable with a logistic link and fixed country effects was used. There were 2,336 (28.75%) individuals who considered having suffered alterations in self-perceived mental health. Unemployed individuals (OR = 1.40; 95%CI: 1.24-1.58), those with bad/regular quality of life (OR = 5.03; 95%CI: 4.01-6.31), and those with high socioeconomic status (OR = 1.66; 95%CI: 1.41-1.96) had a higher risk of self-perceived mental health alterations than those with full-time employment, excellent quality, and low socioeconomic status. According to the fixed-effects model, Brazilians living in the country during the pandemic, who disagreed with their government's decisions (OR = 2.05; 95%CI: 1.74-2.42) and lacked trust in their government (OR = 2.10; 95%CI: 1.74-2.42) had a higher risk of having self-perceived mental health alterations. Nearly 30% of respondents indicated that the COVID-19 pandemic altered their self-perceived mental health. This outcome was associated with political, sociodemographic, and health risk factors. These findings should help policymakers develop post-pandemic community interventions.

Update on olfactory neuroblastoma.

Olfactory neuroblastomas are uncommon malignancies that arise from olfactory receptor cells located high in the nasal cavity. Accurate diagnosis plays a crucial role in determining clinical results and guiding treatment decisions. Diagnosis can be a major challenge for pathologists, especially when dealing with tumours with poor differentiation. The discovery of several molecular and immunohistochemical markers would help to overcome classification difficulties. Due to the paucity of large-scale studies, standardisation of diagnosis, treatment and prediction of outcome remains a challenge. Surgical resection by endoscopic techniques with the addition of postoperative irradiation is the treatment of choice. In addition, it is advisable to consider elective neck irradiation to minimise the risk of nodal recurrence. Molecular characterisation will help not only to make more accurate diagnoses but also to identify specific molecular targets that can be used to develop personalised treatment options tailored to each patient. The present review aims to summarise the current state of knowledge on histopathological diagnosis, the molecular biology and management of this disease.

Autoimmune Hepatitis: A Diagnostic and Therapeutic Overview.

Autoimmune hepatitis is an immune-mediated inflammatory condition of the liver of undetermined cause that affects both sexes, all ages, races, and ethnicities. Its clinical presentation can be very broad, from having an asymptomatic and silent course to presenting as acute hepatitis, cirrhosis, and acute liver failure potentially requiring liver transplantation. The diagnosis is based on histological abnormalities (interface hepatitis), characteristic clinical and laboratory findings (increased aspartate aminotransferase, alanine aminotransferase, and serum IgG concentration), and the presence of one or more characteristic autoantibodies. The large heterogeneity of these clinical, biochemical, and histological findings can sometimes make a timely and proper diagnosis a difficult task. Treatment seeks to achieve remission of the disease and prevent further progression of liver disease. First-line therapy includes high-dose corticosteroids, which are later tapered to decrease side effects, and azathioprine. In the presence of azathioprine intolerance or a poor response to the standard of care, second-line therapy needs to be considered, including mycophenolate mofetil. AIH remains a diagnostic and therapeutic challenge, and a further understanding of the pathophysiological pathways of the disease and the implementation of randomized controlled trials are needed.

Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial.

BACKGROUND: Recently, we found that a new malaria vaccine, R21/Matrix-M, had over 75% efficacy against clinical malaria with seasonal administration in a phase 2b trial in Burkina Faso. Here, we report on safety and efficacy of the vaccine in a phase 3 trial enrolling over 4800 children across four countries followed for up to 18 months at seasonal sites and 12 months at standard sites. METHODS: We did a double-blind, randomised, phase 3 trial of the R21/Matrix-M malaria vaccine across five sites in four African countries with differing malaria transmission intensities and seasonality. Children (aged 5-36 months) were enrolled and randomly assigned (2:1) to receive 5 µg R21 plus 50 µg Matrix-M or a control vaccine (licensed rabies vaccine [Abhayrab]). Participants, their families, investigators, laboratory teams, and the local study team were masked to treatment. Vaccines were administered as three doses, 4 weeks apart, with a booster administered 12 months after the third dose. Half of the children were recruited at two sites with seasonal malaria transmission and the remainder at standard sites with perennial malaria transmission using age-based immunisation. The primary objective was protective efficacy of R21/Matrix-M from 14 days after third vaccination to 12 months after completion of the primary series at seasonal and standard sites separately as co-primary endpoints. Vaccine efficacy against multiple malaria episodes and severe malaria, as well as safety and immunogenicity, were also assessed. This trial is registered on ClinicalTrials.gov, NCT04704830, and is ongoing. FINDINGS: From April 26, 2021, to Jan 12, 2022, 5477 children consented to be screened, of whom 1705 were randomly assigned to control vaccine and 3434 to R21/Matrix-M; 4878 participants received the first dose of vaccine. 3103 participants in the R21/Matrix-M group and 1541 participants in the control group were included in the modified per-protocol analysis (2412 [51·9%] male and 2232 [48·1%] female). R21/Matrix-M vaccine was well tolerated, with injection site pain (301 [18·6%] of 1615 participants) and fever (754 [46·7%] of 1615 participants) as the most frequent adverse events. Number of adverse events of special interest and serious adverse events did not significantly differ between the vaccine groups. There were no treatment-related deaths. 12-month vaccine efficacy was 75% (95% CI 71-79; p<0·0001) at the seasonal sites and 68% (61-74; p<0·0001) at the standard sites for time to first clinical malaria episode. Similarly, vaccine efficacy against multiple clinical malaria episodes was 75% (71-78; p<0·0001) at the seasonal sites and 67% (59-73; p<0·0001) at standard sites. A modest reduction in vaccine efficacy was observed over the first 12 months of follow-up, of similar size at seasonal and standard sites. A rate reduction of 868 (95% CI 762-974) cases per 1000 children-years at seasonal sites and 296 (231-362) at standard sites occurred over 12 months. Vaccine-induced antibodies against the conserved central Asn-Ala-Asn-Pro (NANP) repeat sequence of circumsporozoite protein correlated with vaccine efficacy. Higher NANP-specific antibody titres were observed in the 5-17 month age group compared with 18-36 month age group, and the younger age group had the highest 12-month vaccine efficacy on time to first clinical malaria episode at seasonal (79% [95% CI 73-84]; p<0·001) and standard (75% [65-83]; p<0·001) sites. INTERPRETATION: R21/Matrix-M was well tolerated and offered high efficacy against clinical malaria in African children. This low-cost, high-efficacy vaccine is already licensed by several African countries, and recently received a WHO policy recommendation and prequalification, offering large-scale supply to help reduce the great burden of malaria in sub-Saharan Africa. FUNDING: The Serum Institute of India, the Wellcome Trust, the UK National Institute for Health Research Oxford Biomedical Research Centre, and Open Philanthropy.

Method to obtain a plasma rich in platelet- and plasma-growth factors based on water evaporation.

Platelet-Rich Plasma, also known as PRP, is an autologous biologic product used in medicine as a treatment for tissue repair. Nowadays, the majority of PRP obtention methods enrich only platelets, not considering extraplatelet biomolecules, which take part in several cell processes. In the present work, a novel PRP preparation method was developed to obtain a PRP rich in both platelet and plasma extraplatelet molecules. The method is based on the evaporation of the water of the plasma using a rotary evaporator. With this new methodology an increase in plasmatic growth factors and, as a consequence, a better dermal fibroblast cell viability was achieved, compared to a standard PRP formulation. This novel PRP product obtained with this new methodology showed promising results in vitro as an improved PRP treatment in future application.

Poorly differentiated thyroid carcinomas: conceptual controversy and clinical impact.

Poorly differentiated thyroid carcinomas (PDTC) are rare diseases; nevertheless, they account for the majority of deaths from non-anaplastic follicular cell-derived thyroid carcinomas. Establishing the diagnosis and treatment of PDTC is challenging given the low incidence and the lack of standardization of diagnostic criteria. These limitations hamper the ability to compare therapeutic modalities and outcomes between recent and older studies. Recently, the 5th edition of the classification of endocrine tumors has been published, which includes changes in nomenclature and the addition of the disease entity of "differentiated high-grade follicular cell-derived carcinomas". On the other hand, the recently witnessed advances in molecular diagnostics have enriched therapeutic options and improved prognosis for patients. We herein review the various historical variations and evolution in the diagnostic criteria for PDTC. This systematic review attempts to clarify the evolution of the histological and molecular characteristics of this disease, its prognosis, as well as its treatment options.

The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study.

BACKGROUND: The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa. METHODS: We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR2-10) and ranges from 3% to 65% PfPR2-10. FINDINGS: Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815-333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868-405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4-48) in perennial settings and $6 (3-63) in seasonal settings and the incremental cost per DALY averted was $34 (29-139) in perennial settings and $30 (22-172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2-10. INTERPRETATION: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa. FUNDING: The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.

Two-Pole Nature of the Λ(1405) Resonance from Lattice QCD.

This Letter presents the first lattice QCD computation of the coupled channel πΣ-K[over ¯]N scattering amplitudes at energies near 1405 MeV. These amplitudes contain the resonance Λ(1405) with strangeness S=-1 and isospin, spin, and parity quantum numbers I(J^{P})=0(1/2^{-}). However, whether there is a single resonance or two nearby resonance poles in this region is controversial theoretically and experimentally. Using single-baryon and meson-baryon operators to extract the finite-volume stationary-state energies to obtain the scattering amplitudes at slightly unphysical quark masses corresponding to m_{π}≈200 MeV and m_{K}≈487 MeV, this study finds the amplitudes exhibit a virtual bound state below the πΣ threshold in addition to the established resonance pole just below the K[over ¯]N threshold. Several parametrizations of the two-channel K matrix are employed to fit the lattice QCD results, all of which support the two-pole picture suggested by SU(3) chiral symmetry and unitarity.

Next-generation sequencing reveals remarkable genetic stability in primary and corresponding recurrent intestinal-type sinonasal adenocarcinoma.

BACKGROUND: Recurrent intestinal-type sinonasal adenocarcinoma (ITAC) can occur several years after primary treatment and with different histology. We aimed to clarify if such recurrences could be second primary tumors and to identify actionable mutations as targets for personalized treatment of recurrent ITAC. METHODS: Twelve pairs of primary and recurrent ITAC were histologically examined and analyzed by next-generation sequencing. RESULTS: Histological differences between primary and recurrent tumor pairs were observed in five cases. Frequent mutations included TP53, APC, TSC2, ATM, EPHA2, BRCA2, LRP1B, KRAS, and KMT2B. There was 86% concordance of somatic mutations between the tumor pairs, while four cases carried additional mutations in the recurrence. CONCLUSIONS: We found all cases to be clonal recurrences and not second primary tumors. Moreover, tumor pairs showed a remarkable genomic stability, suggesting that personalized treatment of a recurrence may be based on actionable molecular genetic targets observed in the primary tumor.

Valuing the contribution of sport volunteering to subjective wellbeing: evidence from eight European countries.

Introduction: Volunteering is a prominent and integral aspect of the activities undertaken by sports clubs in Europe. However, even with its growing importance, quantifying the monetary worth of this nonmarket activity, in terms of wellbeing, can present certain difficulties. Traditional approaches to valuing volunteering (i.e., replacement and opportunity cost approaches) do not fully capture the value of volunteering to individuals, as they do not consider the intangible benefits that individuals may derive from their participation. Methods: This research provides added value to the monetisation of volunteering in sport by applying the wellbeing valuation approach (WVA) for the first time to a cross-sectional data in eight European countries. A double instrumental variable approach was developed to correct for unobservable variables that may influence the pairs: income and subjective wellbeing (SWB), and volunteering and SWB. This allows to estimate the causal impact of volunteering and income on SWB more accurately and assign a reasonable monetary value to this non-market activity. Results: The results, based on a sample size of 1,091, show an income compensation for a volunteer, devoting on average 8.7 hours during a four-week period of €16 to €50 per hour, equivalent to between € 1,700 and € 5,200 per year, depending on the nationality of the volunteer. Discussion: With these estimations insights into the value of volunteering in sports are provided, contributing to a better understanding of how this activity can be valued and supported. By recognising and accurately valuing the contributions of volunteers, sport organizations and policymakers can develop more effective strategies for promoting and supporting volunteering in sports.

Assessment of the risk of malignancy in Bethesda III thyroid nodules: a comprehensive review.

The increasing prevalence of thyroid cancer emphasizes the need for a thorough assessment of risk of malignancy in Bethesda III nodules. Various methods ranging commercial platforms of molecular genetic testing (including Afirma® GEC, Afirma® GSC, ThyroSeq® V3, RosettaGX®, ThyGeNEXT®/ThyraMIR®, ThyroidPRINT®) to radionuclide scans and ultrasonography have been investigated to provide a more nuanced comprehension of risk estimation. The integration of molecular studies and imaging techniques into clinical practice may provide clinicians with improved and personalized risk assessment. This integrated approach we feel may enable clinicians to carefully tailor interventions, thereby minimizing the likelihood of unnecessary thyroid surgeries and overall crafting the optimal treatment. By aligning with the evolving landscape of personalized healthcare, this comprehensive strategy ensures a patient-centric approach to thyroid nodule and thyroid cancer management.

Prognostic value of preoperative inflammatory ratios in early glottic cancer treated with transoral laser surgery.

BACKGROUND: There is growing evidence regarding the prognostic utility of ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIII) in head and neck squamous cell carcinoma (HNSCC). However, most studies to date include heterogeneous series with different treatments or tumor subsites. METHODS: We collected data from 201 patients with stage I-II glottic squamous cell carcinoma treated with transoral laser surgery. NLR, PLR, and SIII were calculated from preoperative cell blood count, cut-off points were obtained by ROC curve analysis, and survival rates were calculated. RESULTS: High NLR (p = 0.012) and SIII (p = 0.037), but not PLR (p = 0.48), were associated with worse disease-specific survival (DSS). A similar trend was observed with overall survival (OS), although it did not reach statistical significance. On multivariable analyses, both high NLR (HR = 3.8, 95% CI = 1.5-9.9, p = 0.006) and high SIII (HR = 2.77, 95% CI = 1.1-6.9, p = 0.03) were significantly associated with shortened DSS. CONCLUSIONS: Preoperative NLR and SIII emerge as independent prognostic biomarkers for early-stage surgically treated glottic tumors and could guide individualized follow-up.

Predictors of mechanical ventilation and mortality in critically ill patients with COVID-19 pneumonia / Predictores de ventilación mecánica y mortalidad en pacientes críticos con neumonía por COVID-19

Objective To determine if potential predictors for invasive mechanical ventilation (IMV) are also determinants for mortality in COVID-19-associated acute respiratory distress syndrome (C-ARDS). Design Single center highly detailed longitudinal observational study. Setting Tertiary hospital ICU: two first COVID-19 pandemic waves, Madrid, Spain. Patients or participants : 280 patients with C-ARDS, not requiring IMV on admission. Interventions None. Main variables of interest : Target: endotracheal intubation and IMV, mortality. Predictors: demographics, hourly evolution of oxygenation, clinical data, and laboratory results. Results The time between symptom onset and ICU admission, the APACHE II score, the ROX index, and procalcitonin levels in blood were potential predictors related to both IMV and mortality. The ROX index was the most significant predictor associated with IMV, while APACHE II, LDH, and DaysSympICU were the most with mortality. Conclusions According to the results of the analysis, there are significant predictors linked with IMV and mortality in C-ARDS patients, including the time between symptom onset and ICU admission, the severity of the COVID-19 waves, and several clinical and laboratory measures. These findings may help clinicians to better identify patients at risk for IMV and mortality and improve their management. (AU)

Objetivo Determinar si las variables clínicas independientes que condicionan el inicio de ventilación mecánica invasiva (VMI) son los mismos que condicionan la mortalidad en el síndrome de distrés respiratorio agudo asociado con COVID-19 (C-SDRA). Diseño Estudio observacional longitudinal en un solo centro. Ámbito UCI, hospital terciario: primeras dos olas de COVID-19 en Madrid, España. Pacientes o participantes 280 pacientes con C-SDRA que no requieren VMI al ingreso en UCI. Intervenciones Ninguna. Principales variables de interés Objetivo: VMI y Mortalidad. Predictores: demográficos, variables clínicas, resultados de laboratorio y evolución de la oxigenación. Resultados El tiempo entre el inicio de los síntomas y el ingreso en la UCI, la puntuación APACHE II, el índice ROX y los niveles de procalcitonina en sangre eran posibles predictores relacionados tanto con la IMV como con la mortalidad. El índice ROX fue el predictor más significativo asociada con la IMV, mientras que APACHE II, LDH y DaysSympICU fueron los más influyentes en la mortalidad. Conclusiones Según los resultados obtenidos se identifican predictores significativos vinculados con la VMI y mortalidad en pacientes con C-ARDS, incluido el tiempo entre el inicio de los síntomas y el ingreso en la UCI, la gravedad de las olas de COVID-19 y varias medidas clínicas y de laboratorio. Estos hallazgos pueden ayudar a los médicos a identificar mejor a los pacientes en riesgo de IMV y mortalidad y mejorar su manejo. (AU)

The Importance of Dean Flow in Microfluidic Nanoparticle Synthesis: A ZIF-8 Case Study.

The Dean Flow, a physics phenomenon that accounts for the impact of channel curvature on fluid dynamics, has great potential to be used in microfluidic synthesis of nanoparticles. This study explores the impact of the Dean Flow on the synthesis of ZIF-8 particles. Several variables that influence the Dean Equation (the mathematical expression of Dean Flow) are tested to validate the applicability of this expression in microfluidic synthesis, including the flow rate, radius of curvature, channel cross sectional area, and reagent concentration. It is demonstrated that the current standard of reporting, providing only the flow rate and crucially not the radius of curvature, is an incomplete description that will invariably lead to irreproducible syntheses across different laboratories. An alternative standard of reporting is presented and it is demonstrated how the sleek and simple math of the Dean Equation can be used to precisely tune the final dimensions of high quality, monodisperse ZIF-8 nanoparticles between 40 and 700 nm.