The PI3Kδ inhibitor zandelisib on intermittent dosing in relapsed/refractory follicular lymphoma: Results from a global phase 2 study.

In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune-related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2-8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9-80.4), the complete response (CR) rate was 38% (95% CI, 29.3-47.3), and the median DOR was 16.4 months (95% CI, 9.5-not reached). With a median follow-up of 14.3 months (range, 1-30.5), the median progression-free survival was 11.6 months (95% CI, 8.3-not reached). Twenty-one patients (17%) discontinued therapy due to an adverse event. Grade 3-4 class-related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non-infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class-related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B-cell malignancies.

Application of Mechanistic Multiparameter Optimization and Large-Scale In Vitro to In Vivo Pharmacokinetics Correlations to Small-Molecule Therapeutic Projects.

Computational chemistry and machine learning are used in drug discovery to predict the target-specific and pharmacokinetic properties of molecules. Multiparameter optimization (MPO) functions are used to summarize multiple properties into a single score, aiding compound prioritization. However, over-reliance on subjective MPO functions risks reinforcing human bias. Mechanistic modeling approaches based on physiological relevance can be adapted to meet different potential key objectives of the project (e.g., minimizing dose, maximizing safety margins, and/or minimizing drug-drug interaction risk) while retaining the same underlying model structure. The current work incorporates recent approaches to predict in vivo pharmacokinetic (PK) properties and validates in vitro to in vivo correlation analysis to support mechanistic PK MPO. Examples of use and impact in small-molecule drug discovery projects are provided. Overall, the mechanistic MPO identifies 83% of the compounds considered as short-listed for clinical experiments in the top second percentile, and 100% in the top 10th percentile, resulting in an area under the receiver operating characteristic curve (AUCROC) > 0.95. In addition, the MPO score successfully recapitulates the chronological progression of the optimization process across different scaffolds. Finally, the MPO scores for compounds characterized in pharmacokinetics experiments are markedly higher compared with the rest of the compounds being synthesized, highlighting the potential of this tool to reduce the reliance on in vivo testing for compound screening.

Improved LINE-1 Detection through Pattern Matching by Increasing Probe Length.

Long Interspersed Element-1 (LINE-1 or L1) is an autonomous transposable element that accounts for 17% of the human genome. Strong correlations between abnormal L1 expression and diseases, particularly cancer, have been documented by numerous studies. L1PD (LINE-1 Pattern Detection) had been previously created to detect L1s by using a fixed pre-determined set of 50-mer probes and a pattern-matching algorithm. L1PD uses a novel seed-and-pattern-match strategy as opposed to the well-known seed-and-extend strategy employed by other tools. This study discusses an improved version of L1PD that shows how increasing the size of the k-mer probes from 50 to 75 or to 100 yields better results, as evidenced by experiments showing higher precision and recall when compared to the 50-mers. The probe-generation process was updated and the corresponding software is now shared so that users may generate probes for other reference genomes (with certain limitations). Additionally, L1PD was applied to other non-human genomes, such as dogs, horses, and cows, to further validate the pattern-matching strategy. The improved version of L1PD proves to be an efficient and promising approach for L1 detection.

Balanced Permeability Index: A Multiparameter Index for Improved In Vitro Permeability.

The optimization of passive permeability is a key objective for orally available small molecule drug candidates. For drugs targeting the central nervous system (CNS), minimizing P-gp-mediated efflux is an additional important target for optimization. The physicochemical properties most strongly associated with high passive permeability and lower P-gp efflux are size, polarity, and lipophilicity. In this study, a new metric called the Balanced Permeability Index (BPI) was developed that combines these three properties. The BPI was found to be more effective than any single property in classifying molecules based on their permeability and efflux across a diverse range of chemicals and assays. BPI is easy to understand, allowing researchers to make decisions about which properties to prioritize during the drug development process.

Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma.

The mitochondrial genome (mtDNA) encodes essential machinery for oxidative phosphorylation and metabolic homeostasis. Tumor mtDNA is among the most somatically mutated regions of the cancer genome, but whether these mutations impact tumor biology is debated. We engineered truncating mutations of the mtDNA-encoded complex I gene, Mt-Nd5, into several murine models of melanoma. These mutations promoted a Warburg-like metabolic shift that reshaped tumor microenvironments in both mice and humans, consistently eliciting an anti-tumor immune response characterized by loss of resident neutrophils. Tumors bearing mtDNA mutations were sensitized to checkpoint blockade in a neutrophil-dependent manner, with induction of redox imbalance being sufficient to induce this effect in mtDNA wild-type tumors. Patient lesions bearing >50% mtDNA mutation heteroplasmy demonstrated a response rate to checkpoint blockade that was improved by ~2.5-fold over mtDNA wild-type cancer. These data nominate mtDNA mutations as functional regulators of cancer metabolism and tumor biology, with potential for therapeutic exploitation and treatment stratification.

Development of a Screening Method for Fluoroquinolones in Meat Samples Using Molecularly Imprinted Carbon Dots.

An accurate and simple screening method has been developed for the determination of fluoroquinolone antibiotics. Carbon dots were synthesized by simple hydrothermal treatment as highly fluorescent nano-sensors. They were subsequently used in the synthesis of organic-based molecularly imprinted polymers to develop fluorescence-based polymeric composites using enoxacin as a representative dummy template molecule of fluoroquinolones. The method was optimized concerning the pH of the medium and composite concentration. The normalized fluorescence intensity showed efficient quenching under optimized conditions upon successive addition of the template, with an excellent correlation coefficient. The proposed method was applied to eight other fluoroquinolones, exhibiting, in all cases, good correlation coefficients (0.65-0.992) within the same linearity range (0.03-2.60 mg mL-1). Excellent detection and quantification limits were been obtained for the target analytes down to 0.062 and 0.186 mg L-1, respectively. All studied analytes showed no interference with enrofloxacin, the most commonly used veterinary fluoroquinolone, with a percentage of cross-reactivity varying from 89.00 to 540.00%. This method was applied successfully for the determination of enrofloxacin in three different types of meat samples: beef, pork, and chicken, with good recoveries varying from 70 to 100% at three levels. This new procedure is an easy analytical method that can be useful as a screening method for monitoring the environmental hazard of fluoroquinolones in quality control laboratories.

The earliest basketry in southern Europe: Hunter-gatherer and farmer plant-based technology in Cueva de los Murciélagos (Albuñol).

Plant material culture can offer unique insights into the ways of life of prehistoric societies; however, its perishable nature has prevented a thorough understanding of its diverse and complex uses. Sites with exceptional preservation of organic materials provide a unique opportunity for further research. The burial site of Cueva de los Murciélagos in southern Iberia, uncovered during 19th-century mining activities, contained the best-preserved hunter-gatherer basketry in southern Europe, together with other unique organic artifacts associated with the first farming communities, such as sandals and a wooden hammer. We present 14 14C dates for the perishable artifacts (N = 76), situating the assemblage between the Early and Middle Holocene (c. 7500 to 4200 cal BCE). Our integrated analysis includes raw material determination and technological and chrono-cultural contextualization of this unique and important set of materials.

Zanubrutinib: past, present, and future.

In recent years, Bruton tyrosine kinase (BTK) inhibitors have provided significant advances in the treatment of patients with B-cell malignancies. Ibrutinib was the first BTK inhibitor to be approved, and it changed the standard-of-care treatment for diseases such as chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia, improving efficacy outcomes and safety compared to chemotherapy. In this article, we review the development of zanubrutinib, a next-generation BTK inhibitor, from molecular design to patient-related outcomes. We start this journey by providing insights into the discovery of BTK and the physiologic, genetic, and molecular characterization of patients lacking this kinase, together with the brief treatment landscape in the era of chemo-immunotherapies. Zanubrutinib was originally developed by applying a structure-activity strategy to enhance the specificity as well as enzymatic and pharmacokinetic properties. Preclinical studies confirmed greater specificity and better bioavailability of zanubrutinib compared with that of ibrutinib, which supported the initiation of clinical trials in humans. Preliminary clinical results indicated activity in B-cell malignancies together with an improved safety profile, in line with less off-target effects described in the preclinical studies. The clinical program of zanubrutinib has since expanded significantly, with ongoing studies in a wide range of hemato-oncological diseases and in combination with many other therapies. Zanubrutinib currently is approved for various B-cell malignancies in multiple countries. This story highlights the importance of multidisciplinary collaborative research, from bench to bedside, and provides an example of how the commitment to finding improved treatment options should always run parallel to patient care.

Risk factors for functional dyspepsia, erosive and non-erosive gastroesophageal reflux disease: A cross-sectional study / Factores de riesgo en dispepsia funcional y enfermedad por reflujo gastroesofágico: un estudio transversal

Background: Conflicting data exists regarding risk factors associated with Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Few studies examine anxiety/depression in relation to GERD phenotypes (Esophagitis/EE, and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes. Our aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as their relationship with anxiety/depression. Methods: 338 subjects were selected from 357 patients referred to three tertiary-centers for endoscopic evaluation. Every subject was interviewed individually to administer three validated questionnaires: GERD-Q, Rome-IV and HADS. Results: 45/338 patients were controls, 198/58.6% classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD. Conclusions: NERD and FD share demographic and psychopathological risk factors which suggests that they may form part of the same pathophysiological spectrum. Regarding NERD anxiety was predominant, and in FD anxiety+depression, suggesting that both processes may require complementary psychological therapy.(AU)

Antecedentes: Existen datos controvertidos sobre los factores de riesgo asociados a la enfermedad por reflujo gastroesofágico (ERGE) y la dispepsia funcional (DF). Pocos estudios han evaluado la relación entre ansiedad/depresión y los diferentes fenotipos de la DF (criterios Roma IV) y de la ERGE (erosiva [EE] y no erosiva [NERD]). Nuestro objetivo fue valorar la asociación entre diferentes factores epidemiológicos y comorbilidades y los fenotipos de la ERGE, la DF y sus síndromes, y su relación con la ansiedad/depresión. Métodos: Se seleccionaron 338 pacientes entre 357 remitidos para estudio endoscópico en 3 hospitales terciarios. Cada uno fue entrevistado individualmente y completó 3 cuestionarios validados: GERD-Q, Roma IV y HADS. Resultados: Cuarenta y cinco de los 338 pacientes fueron controles. Se clasificaron 198/58,6% como ERGE, 81/24,0% como EE (49/14,5% sintomática y 32/9,5% asintomática), 117/34,6% como NERD y 176/52,1% como DF (43/12,7% síndrome de dolor epigástrico, 36/10,7% síndrome de molestias posprandiales y 97/28,7% solapamiento epigastralgia-molestias posprandiales). Ochenta y uno solapaban ERGE-DF. El análisis multivariante encontró las siguientes asociaciones significativas: edad en NERD y DF; sexo en EE, EE asintomática y DF; IMC en NERD y DF; alcohol en EE; ansiedad/depresión en DF; toma de antagonistas del calcio en EE e inhaladores en DF. Al comparar el grupo control vs. diferentes grupos/subgrupos encontramos significativamente más ansiedad en NERD, solapamiento DF-ERGE, DF y todos sus síndromes Roma IV; más depresión en DF, solapamientos epigastralgia-molestias posprandiales y ERGE-DF; y más ansiedad+depresión en NERD, DF y solapamientos epigastralgia-molestias posprandiales y ERGE-DF. Conclusiones: La DF y la NERD comparten factores de riesgo demográficos y psicopatológicos, lo que evidencia que forman parte de un mismo espectro fisiopatológico...(AU)

Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study.

Up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) are refractory to or relapse after first-line therapy, highlighting the need for better treatments. Mosunetuzumab is a CD20 × CD3 bispecific antibody that engages and redirects T cells to eliminate malignant B cells. In this phase 2, open-label study (NCT03677141), 40 patients (52.5% with international prognostic index ≥3) with previously untreated DLBCL initiated 6 cycles of IV mosunetuzumab with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Mosunetuzumab was administered in cycle 1 as step-up doses to mitigate cytokine release syndrome [CRS], and a dose of 30 mg was given on day 1 of cycles 2-6. Efficacy end points included objective and complete response rates, as determined by the investigator, via positron emission tomography-computed tomography, using Lugano 2014 criteria (87.5% and 85.0%, respectively). At a median follow-up of 32.0 months, the estimated 2-year progression-free survival and event-free survival rates were 65.4% (95% confidence interval [CI], 49.5-81.4) and 60.4% (95% CI, 44.7-76.1), respectively. CRS occurred in 60.0% of patients; all events were grade 1 (45.0%) or grade 2 (15.0%) and occurred primarily in cycle 1. Mosunetuzumab-related grade ≥3 neurologic adverse events (AEs) potentially consistent with immune effector cell-associated neurotoxicity syndrome occurred in 1 patient (2.5%). Grade 5 AEs were reported in 2 patients. Neutropenia occurred in 70.0% of patients, mostly during cycle 1 and was of short duration. These findings demonstrate promising activity and a manageable safety profile for mosunetuzumab-CHOP and warrant further investigation of mosunetuzumab in first-line combination regimens for DLBCL.

Defining the first bona fide cell model for SMARCA4-deficient, undifferentiated tumor.

The World Health Organization's tumor classification guidelines are frequently updated and renewed as knowledge of cancer biology advances. For instance, in 2021, a novel lung tumor subtype named SMARCA4-deficient, undifferentiated tumor (SMARCA4-dUT, code 8044/3) was included. To date, there is no defined cell model for SMARCA4-dUT that could be used to help thoracic clinicians and researchers in the study of this newly defined tumor type. As this tumor type was recently described, it is feasible that some cell models formerly classified as lung adenocarcinoma (LUAD) could now be better classified as SMARCA4-dUT. Thus, in this work, we aimed to identify a bona fide cell model for the experimental study of SMARCA4-dUT. We compared the differential expression profiles of 36 LUAD-annotated cell lines and 38 cell lines defined as rhabdoid in repositories. These comparative results were integrated with the mutation and expression profiles of the SWI/SNF complex members, and they were surveyed for the presence of the SMARCA4-dUT markers SOX2, SALL4, and CD34, measured by RT-qPCR and western blotting. Finally, the cell line with the paradigmatic SMARCA4-dUT markers was engrafted into immunocompromised mice to assess the histological morphology of the formed tumors and compare them with those formed by a bona fide LUAD cancer cell line. NCI-H522, formerly classified as LUAD, displayed expression profiles nearer to rhabdoid tumors than LUAD tumors. Furthermore, NCI-H522 has most of the paradigmatic features of SMARCA4-dUT: hemizygous inactivating mutation of SMARCA4, severe SMARCA2 downregulation, and high-level expression of stem cell markers SOX2 and SALL4. In addition, the engrafted tumors of NCI-H522 did not display a typical differentiated glandular structure as other bona fide LUAD cell lines (A549) do but had rather a largely undifferentiated morphology, characteristic of SMARCA4-dUT. Thus, we propose the NCI-H522 as the first bona fide cell line model of SMARCA4-dUT. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Clinical advances in epigenetic therapies for lymphoma.

BACKGROUND: Advances in understanding of cancer biology, genomics, epigenomics, and immunology have resulted in development of several therapeutic options that expand cancer care beyond traditional chemotherapy or radiotherapy, including individualized treatment strategies, novel treatments based on monotherapies or combination therapy to reduce toxicities, and implementation of strategies for overcoming resistance to anticancer therapy. RESULTS: This review covers the latest applications of epigenetic therapies for treatment of B cell, T cell, and Hodgkin lymphomas, highlighting key clinical trial results with monotherapies and combination therapies from the main classes of epigenetic therapies, including inhibitors of DNA methyltransferases, protein arginine methyltransferases, enhancer of zeste homolog 2, histone deacetylases, and the bromodomain and extraterminal domain. CONCLUSION: Epigenetic therapies are emerging as an attractive add-on to traditional chemotherapy and immunotherapy regimens. New classes of epigenetic therapies promise low toxicity and may work synergistically with other cancer treatments to overcome drug resistance mechanisms.

Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium.

PURPOSE: Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory mantle cell lymphoma (MCL). This therapy was approved on the basis of the single-arm phase II ZUMA-2 trial, which showed best overall and complete response rates of 91% and 68%, respectively. We report clinical outcomes with brexu-cel in the standard-of-care setting for the approved indication. PATIENTS AND METHODS: Patients who underwent leukapheresis between August 1, 2020 and December 31, 2021, at 16 US institutions, with an intent to manufacture commercial brexu-cel for relapsed/refractory MCL, were included. Patient data were collected for analyses of responses, outcomes, and toxicities as per standard guidelines. RESULTS: Of 189 patients who underwent leukapheresis, 168 (89%) received brexu-cel infusion. Of leukapheresed patients, 79% would not have met ZUMA-2 eligibility criteria. Best overall and complete response rates were 90% and 82%, respectively. At a median follow-up of 14.3 months after infusion, the estimates for 6- and 12-month progression-free survival (PFS) were 69% (95% CI, 61 to 75) and 59% (95% CI, 51 to 66), respectively. The nonrelapse mortality was 9.1% at 1 year, primarily because of infections. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 8% and 32%, respectively. In univariable analysis, high-risk simplified MCL international prognostic index, high Ki-67, TP53 aberration, complex karyotype, and blastoid/pleomorphic variant were associated with shorter PFS after brexu-cel infusion. Patients with recent bendamustine exposure (within 24 months before leukapheresis) had shorter PFS and overall survival after leukapheresis in intention-to-treat univariable analysis. CONCLUSION: In the standard-of-care setting, the efficacy and toxicity of brexu-cel were consistent with those reported in the ZUMA-2 trial. Tumor-intrinsic features of MCL, and possibly recent bendamustine exposure, may be associated with inferior efficacy outcomes.

Risk factors for functional dyspepsia, erosive and non-erosive gastroesophageal reflux disease: A cross-sectional study.

BACKGROUND: Conflicting data exists regarding risk factors associated with Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Few studies examine anxiety/depression in relation to GERD phenotypes (Esophagitis/EE, and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes. Our aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as their relationship with anxiety/depression. METHODS: 338 subjects were selected from 357 patients referred to three tertiary-centers for endoscopic evaluation. Every subject was interviewed individually to administer three validated questionnaires: GERD-Q, Rome-IV and HADS. RESULTS: 45/338 patients were controls, 198/58.6% classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD. CONCLUSIONS: NERD and FD share demographic and psychopathological risk factors which suggests that they may form part of the same pathophysiological spectrum. Regarding NERD anxiety was predominant, and in FD anxiety+depression, suggesting that both processes may require complementary psychological therapy.

The Ultratrace Determination of Fluoroquinolones in River Water Samples by an Online Solid-Phase Extraction Method Using a Molecularly Imprinted Polymer as a Selective Sorbent.

Fluoroquinolones (FQs) are broad-spectrum antibiotics widely used to treat animal and human infections. The use of FQs in these activities has increased the presence of antibiotics in wastewater and food, triggering antimicrobial resistance, which has severe consequences for human health. The detection of antibiotics residues in water and food samples has attracted much attention. Herein, we report the development of a highly sensitive online solid-phase extraction methodology based on a selective molecularly imprinted polymer (MIP) and fluorescent detection (HPLC-FLD) for the determination of FQs in water at low ng L−1 level concentration. Under the optimal conditions, good linearity was obtained ranging from 0.7 to 666 ng L−1 for 7 FQs, achieving limits of detection (LOD) in the low ng L−1 level and excellent precision. Recoveries ranged between 54 and 118% (RSD < 17%) for all the FQs tested. The method was applied to determining FQs in river water. These results demonstrated that the developed method is highly sensitive and selective.

Manejo de las fracturas maxilofaciales y sus complicaciones / Management of maxillofacial fractures and its complications

RESUMEN Antecedentes: el trauma maxilofacial corresponde a toda lesión traumática del macizo facial. Actualmente representa uno de los problemas de salud más importantes en el mundo. Nuestro objetivo es realizar un análisis de nuestra experiencia en las intervenciones realizadas en pacientes internados y sus complicaciones. Material y métodos: se realizó un estudio descriptivo, retrospectivo y observacional de 205 pacientes con fracturas maxilofaciales desde el año 2011 hasta el año 2019. Resultados: el 81,46% fueron hombres (n: 167) y el rango etario más afectado osciló entre los 21 y 30 años con el 38,54% (n:79). El accidente de tránsito 56,1% (n:115) fue el mecanismo de trauma más frecuente. Los tipos de fracturas faciales fueron: panfaciales 12,2% (n: 25), tercio superior 1,46% (n:3), tercio medio 72,2% (n:148) y tercio inferior 14,15% (n:29). Dentro del tercio superior, el 66,67% (n:2) fueron fracturas del seno frontal asociadas al hueso frontal, en el tercio medio las combinadas en un 54,73% (n:81) y en el tercio inferior, las complejas en el 34,48% (n:10). Fueron intervenidos 199 pacientes (97,07%). Solo el 11,56% (n:23) presentó alguna complicación. No se observaron complicaciones graves. Discusión: según nuestra serie, la mayoría de los pacientes fueron hombres jóvenes; la causa más frecuente, el accidente de tránsito, y el tercio medio, el más afectado, resultados estos similares a los de otros estudios publicados. El tratamiento quirúrgico fue principalmente reducción abierta y fijación con material de osteosíntesis de titanio, un procedimiento seguro y fiable, que permite restablecer la funcionalidad previa al traumatismo, con un índice muy bajo de complicaciones posoperatorias.

ABSTRACT Background: Maxillofacial trauma corresponds to all traumatic injuries affecting the facial bones. Nowadays, it represents one of the main healthcare issues worldwide. The aim of this study is to analyze our experience in the interventions performed in hospitalized and their complications. Material and methods: We performed a retrospective and observational study of 205 patients with maxillofacial fractures from 2011 to 2019. Results: 81.46% were men (n = 167) and 38.54% (n = 79) of the patients were between 21 and 30 years of age. Traffic collision was the most common mechanism of trauma (56,1%, n = 115). The types of facial fractures were panfacial (12.2%; n = 25), of the upper-third (1.43%; n = 3), of the middle-third (72.2%; n = 148) and of the lower third (14.15%; n = 29). In the upper third of the face frontal sinus fractures associated with the frontal bone were the most common (66.67%; n =2); in the middle-third combined fractures were most prevalent (54.73%; n = 81) while complex fractures were most frequent in the lower third (34,48%; n = 10). One-hundred and ninety-one patients were operated on (97.07%). Complications occurred in only 11.56% (n = 23) and were not serious. Discusion: In our series, most patients were young men, traffic collisions were the most common cause of trauma, and the middle third of the face was the most affected region. These results are similar to our publications. Surgical management, mostly by open reduction and fixation with titanium-based osteosynthesis material, is an effective, safe and reliable procedure, which allows the restoration of pre-trauma function, with very low rate of postoperative complications.

A paradigm shift in the quantification of wave energy attenuation due to saltmarshes based on their standing biomass.

Most existing analytical and numerical models to quantify wave energy attenuation attributed to saltmarshes are based on the definition of a drag coefficient that varies with vegetation and wave characteristics and requires calibration, i.e., a case-specific variable. With the aim of determining a new variable to estimate wave energy attenuation without the use of calibration coefficients, wave attenuation caused by different saltmarsh species and the relationship with the ecosystem standing biomass are experimentally studied. Samples of four real saltmarshes with contrasting morphological and biomechanical properties, namely, Spartina sp., Salicornia sp., Halimione sp. and Juncus sp., are collected in the field and placed in a wave flume for testing under different regular and random wave conditions. Two meadow densities are considered, in addition to zero-density cases. Thus, wave damping coefficients are obtained in vegetated cases, ß, and bare soil cases, ßB, and wave damping produced solely by the meadow standing biomass, ßSB, is determined. The obtained wave damping coefficients are related to a new variable, the hydraulic standing biomass (HSB), which is defined as a function of the meadow mean height and standing biomass and incident flow characteristics. Linear fitting relationships between the wave damping coefficient and HSB are obtained, allowing ß and ßSB estimation without the need for calibration. Therefore, the use of these new relationships facilitates direct quantification of wave energy attenuation due to saltmarshes based on incident wave conditions, mean plant height and meadow standing biomass, variables that can be obtained from aerial images or remote sensing data, extending the applicability of the approach. Another key aspect is that this approach does not depend on any calibration coefficient and can be directly applied with knowledge of the abovementioned characteristics. This may represent a paradigm shift in the estimation of wave energy attenuation attributed to saltmarshes.

Impact of COVID-19 on Respiratory Admissions in a Tertiary Pediatric Intensive Care Unit.

Background Pediatric inpatient admissions for viral respiratory infections decreased worldwide during the early part of the coronavirus disease 2019 (COVID-19) pandemic. This was likely due to social distancing measures and mask mandates leading to a decreased spread of viruses. We question if there was an increase in respiratory admissions during the winter of 2020-2021 due to the overlap of seasonal respiratory viruses and COVID-19 and the severity of those admissions. Methods We performed a single-center retrospective chart review of all respiratory admissions to our pediatric intensive care unit (PICU) from October to April during the years 2018-2019, 2019-2020, and 2020-2021. We compared the total number of respiratory admissions from different viruses and respiratory admissions by diagnoses among those time periods. Second, we compared the PICU length of stay and duration of mechanical ventilation (both invasive and non-invasive) for these respiratory admissions during those years. Results We saw a drastic decrease in the total respiratory admissions to the PICU in 2020-2021 compared to the same period of time in the last two years. The greatest contributor to this decrease was admissions secondary to bronchiolitis. We noticed a statistically significant decrease in both asthma (p<0.001) and chronic respiratory failure admissions (p=0.0029) during the pandemic winter compared to previous winters. Although, the total number of all respiratory viral admissions is not significant, admissions specific to the respiratory syncytial virus (RSV) (p<0.0001), rhino-enterovirus (p<0.0001), and multi-virus (p=0.0016), achieved statistical significance. There was no statistical difference between the PICU length of stay and duration of mechanical ventilation during the three years. Conclusion Despite a decrease in pediatric respiratory admissions during the COVID-19 pandemic, the severity of illness based on length of stay in the PICU and length of time on respiratory support remains unchanged compared to the previous two years.