Impact of antibiotic prophylaxis in second-stage surgery in joint prosthesis infection treated with two-stage exchange. A multicenter case-control study.

INTRODUCTION: After two-stage exchange due to prosthetic joint infection (PJI), the new prosthesis carries a high risk of reinfection (RePJI). There isn`t solid evidence regarding the antibiotic prophylaxis in 2nd-stage surgery. The objective of this study is to describe what antibiotic prophylaxis is used in this surgery and evaluate its impact on the risk of developing RePJI. METHODS: Retrospective multicenter case-control study in Spanish hospitals. The study included cases of PJI treated with two-stage exchange and subsequently developed a new infection. For each case, two controls were included, matched by prosthesis location, center, and year of surgery. The prophylaxis regimens were grouped based on their antibacterial spectrum, and we calculated the association between the type of regimen and the development of RePJI using conditional logistic regression, adjusted for possible confounding factors. RESULTS: We included 90 cases from 12 centers, which were compared with 172 controls. The most frequent causative microorganism was Staphylococcus epidermidis with 34 cases (37.8%). Staphylococci were responsible for 50 cases (55.6%), 32 of them (64%) methicillin-resistant. Gram-negative bacilli were involved in 30 cases (33.3%), the most common Pseudomonas aeruginosa. In total, 83 different antibiotic prophylaxis regimens were used in 2nd-stage surgery, the most frequent a single preoperative dose of cefazolin (48 occasions; 18.3%); however, it was most common a combination of a glycopeptide and a beta-lactam with activity against Pseudomonas spp (99 cases, 25.2%). In the adjusted analysis, regimens that included antibiotics with activity against methicillin-resistant staphylococci AND Pseudomonas spp were associated with a significantly lower risk of RePJI (adjusted OR = 0.24; 95% IC: 0.09-0.65). CONCLUSIONS: The lack of standardization in 2nd-satge surgery prophylaxis explains the wide diversity of regimens used in this procedure. The results suggest that antibiotic prophylaxis in this surgery should include an antibiotic with activity against methicillin-resistant staphylococci and Pseudomonas.

Recombinant human soluble domain of CD39L3 and ticagrelor: cardioprotective effects in experimental myocardial infarction.

BACKGROUND AND AIMS: The ecto-nucleoside triphosphate diphosphohydrolases of the CD39 family degrade ATP and ADP into AMP, which is converted into adenosine by the extracellular CD73/ecto-5-nucleotidase. This pathway has been explored in antithrombotic treatments but little in myocardial protection. We have investigated whether the administration of solCD39L3 (AZD3366) confers additional cardioprotection to that of ticagrelor alone in a pre-clinical model of myocardial infarction (MI). METHODS: Ticagrelor-treated pigs underwent balloon-induced MI (90 min) and, before reperfusion, received intravenously either vehicle, 1 mg/kg AZD3366 or 3 mg/kg AZD3366. All animals received ticagrelor twice daily for 42 days. A non-treated MI group was run as a control. Serial cardiac magnetic resonance (baseline, Day 3 and Day 42 post-MI), light transmittance aggregometry, bleeding time, and histological and molecular analyses were performed. RESULTS: Ticagrelor reduced oedema formation and infarct size at Day 3 post-MI vs. controls. A 3 mg/kg AZD3366 provided an additional 45% reduction in oedema and infarct size compared with ticagrelor and a 70% reduction vs. controls (P < .05). At Day 42, infarct size declined in all ticagrelor-administered pigs, particularly in 3 mg/kg AZD3366-treated pigs (P < .05). Left ventricular ejection fraction was diminished at Day 3 in placebo pigs and worsened at Day 42, whereas it remained unaltered in ticagrelor ± AZD3366-administered animals. Pigs administered with 3 mg/kg AZD3366 displayed higher left ventricular ejection fraction upon dobutamine stress at Day 3 and minimal dysfunctional segmental contraction at Day 42 (χ2P < .05 vs. all). Cardiac and systemic molecular readouts supported these benefits. Interestingly, AZD3366 abolished ADP-induced light transmittance aggregometry without affecting bleeding time. CONCLUSIONS: Infusion of AZD3366 on top of ticagrelor leads to enhanced cardioprotection compared with ticagrelor alone.

Natural history and prognostic factors of candidemia in kidney transplant recipients: A retrospective, multinational study.

BACKGROUND: The natural history of candidemia in kidney transplant recipients (KTR) remains poorly understood. This study aimed to evaluate mortality, prognostic factors and overall graft loss after candidemia in KTRs. METHODS: This is a retrospective multicentre study enrolling all KTRs ≥15 years old with candidemia diagnosed at hospitals in Brazil, Spain and Italy from 2010 to 2020. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors of 14-day mortality and overall graft loss. RESULTS: We enrolled 93 KTRs of which 75 were from Brazil. The mean time interval from transplantation to the onset of candidemia was 45.2 ± 61.5 months. 42% of all patients were on haemodialysis, 31.3% had an episode of sepsis and 39% underwent surgery within 30 days before fungemia. European patients were more likely to receive echinocandin (32 vs. 72%, p < .001). 22.7% of Brazilian patients did not receive any antifungal before death. All-cause mortality at 14 days was higher in Brazil (41.3 vs. 11.1%, p = .016). Candida colonisation (OR 6.91 [95% CI: 1.08-44.3], p = .042) and hypotension (OR 4.87 [95% CI: 1.62-14.66], p = .005) were associated with 14-day mortality. Echinocandin treatment had a protective effect (OR 0.19 [95% CI: 0.05-0.73], p = .015). Graft loss at 90 days occurred in 48% of patients (70.7 in Brazil vs. 22.2% in Europe, p < .01). CONCLUSIONS: Candidemia in KTR is usually documented late after engraftment in patients requiring HD, surgical procedures and dysbiosis secondary to antibiotic use. Mortality was higher in Brazil. Echinocandin therapy was associated with improved survival.

Multicenter Retrospective Andalusian Study of the Use of Sonidegib for the Treatment of Local Advanced Basal Cell Carcinoma in Real Clinical Practice.

INTRODUCTION: Locally advanced basal cell carcinoma (LA-BCC) is defined as that BCC in which there is radiological confirmation of invasion of certain neighboring structures in depth and also, usually, a BCC that is of a sufficient size and invasion (although there is no radiological demonstration of deep invasion) in which surgery and radiotherapy are not adequate, are insufficient or are contraindicated to achieve the cure of the tumor, either due to characteristics of the tumor itself or of the patient. Sonidegib is indicated for the treatment of adult patients with locally advanced basal cell carcinoma that is not amenable to curative surgery or radiotherapy. MATERIAL AND METHODS: This is a retrospective, multicenter and descriptive study in nine centers in Andalusia, Spain. Patients treated with sonidegib for >3 months for locally advanced BCC were included from 1 January 2021 to 1 January 2023. Epidemiological, efficacy and safety data were collected. RESULTS: In the present study, a total of 38 patients were included, with a median age of 76.23 years (range 40-101). Prior treatment was surgery (31.57%; n = 25), radiotherapy (15.78%; n = 6), vismodegib (31.57%; n = 12). Eleven patients had not received prior treatment. LA-BCC were located in the cephalic pole, face or scalp. There was a total response in 9/38 patients (23.7%), partial response in 25/38 patients (65.8%) and no response in 4 patients (10.52%). In 6/34 patients, the dose was reduced to 200 mg every other day until it was discontinued due to adverse effects. The main adverse effects reported were dysgeusia (n = 8), asthenia (n = 8), = 6), muscle spasms (n = 6), alopecia (n = 4) and gastrointestinal intolerance (n = 4). DISCUSSION: Sonidegib is the second iHh authorized for the treatment of adult patients with locally advanced BCC who are not amenable to curative surgery or radiotherapy, based on the results of the phase II clinical trial, BOLT. Sonidegib shows good effectiveness and an acceptable safety profile in routine clinical practice in the sample presented.

Slow flow mimicking pulmonary embolism.

A man in his 70s in a rehabilitation hospital, post cerebral infarct, became acutely short of breath with reduced oxygen saturations and an elevated d-dimer.Non-occlusive filling defects were noted on the CT pulmonary angiogram in the proximal left pulmonary arteries. There was associated hypoplasia of the distal pulmonary arterial tree in the left hemithorax with left pulmonary vein stenosis. Review of previous imaging suggested this oligaemia was longstanding.Although filling defects in the pulmonary arteries usually correspond to embolic material, in our patient they were too dense to represent thrombus and probably represented flow-related artefacts in the setting of chronic air trapping.Given the associated volume loss, bronchiectasis and bronchial wall thickening in the left hemithorax Swyer-James-McLeod syndrome was thought to be the most likely underlying cause.

Loss of microRNA-30a and sex-specific effects on the neonatal hyperoxic lung injury.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is characterized by an arrest in lung development and is a leading cause of morbidity in premature neonates. It has been well documented that BPD disproportionally affects males compared to females, but the molecular mechanisms behind this sex-dependent bias remain unclear. Female mice show greater preservation of alveolarization and angiogenesis when exposed to hyperoxia, accompanied by increased miR-30a expression. In this investigation, we tested the hypothesis that loss of miR-30a would result in male and female mice experiencing similar impairments in alveolarization and angiogenesis under hyperoxic conditions. METHODS: Wild-type and miR-30a-/- neonatal mice were exposed to hyperoxia [95% FiO2, postnatal day [PND1-5] or room air before being euthanized on PND21. Alveolarization, pulmonary microvascular development, differences in lung transcriptome, and miR-30a expression were assessed in lungs from WT and miR-30a-/- mice of either sex. Blood transcriptomic signatures from preterm newborns (with and without BPD) were correlated with WT and miR-30a-/- male and female lung transcriptome data. RESULTS: Significantly, the sex-specific differences observed in WT mice were abrogated in the miR-30a-/- mice upon exposure to hyperoxia. The loss of miR-30a expression eliminated the protective effect in females, suggesting that miR-30a plays an essential role in regulating alveolarization and angiogenesis. Transcriptome analysis by whole lung RNA-Seq revealed a significant response in the miR-30a-/- female hyperoxia-exposed lung, with enrichment of pathways related to cell cycle and neuroactive ligand-receptor interaction. Gene expression signature in the miR-30a-/- female lung associated with human BPD blood transcriptomes. Finally, we showed the spatial localization of miR-30a transcripts in the bronchiolar epithelium. CONCLUSIONS: miR-30a could be one of the biological factors mediating the resilience of the female preterm lung to neonatal hyperoxic lung injury. A better understanding of the effects of miR-30a on pulmonary angiogenesis and alveolarization may lead to novel therapeutics for treating BPD.

Bronchopulmonary dysplasia (BPD) is a lung condition that affects babies born prematurely, causing problems with their lung development. Interestingly, BPD tends to affect boys more than girls, but we do not fully understand why. To investigate this, we conducted a study using mice. Female mice had better lung development and blood vessel formation when exposed to high oxygen levels. We found higher expression of a molecule called miR-30a in the female mice and seemed to be protective. So, we wanted to see if removing miR-30a would have the same effect on both male and female mice. To test this, we exposed newborn mice without miR-30a and normal mice to high oxygen levels or regular room air. Interestingly, the differences between normal males and females were no longer present in the mice without miR-30a. This suggested that miR-30a plays an important role in lung development. We also identified that the female mice without miR-30a, when exposed to high oxygen, had the greatest number of genes affected, and these gene changes were like those seen in blood samples from premature babies with BPD. Finally, we report that miR-30a was in a specific part of the lung called the bronchiolar epithelium. Overall, this study suggests that miR-30a is crucial in protecting premature lungs from damage caused by high oxygen levels. By understanding how miR-30a affects lung development, we may be able to develop new treatments for BPD in the future.

Endothelial to mesenchymal transition in neonatal hyperoxic lung injury: role of sex as a biological variable.

Bronchopulmonary dysplasia (BPD) is characterized by an arrest in alveolarization, abnormal vascular development, and variable interstitial fibroproliferation in the premature lung. Endothelial to mesenchymal transition (EndoMT) may be a source of pathological fibrosis in many organ systems. Whether EndoMT contributes to the pathogenesis of BPD is not known. We tested the hypothesis that pulmonary endothelial cells will show increased expression of EndoMT markers upon exposure to hyperoxia and that sex as a biological variable will modulate differences in expression. Wild-type (WT) and Cdh5-PAC CreERT2 (endothelial reporter) neonatal male and female mice (C57BL6) were exposed to hyperoxia (0.95 [Formula: see text]) either during the saccular stage of lung development (95% [Formula: see text]; postnatal day 1-5 [PND1-5]) or through the saccular and early alveolar stages of lung development (75% [Formula: see text]; PND1-14). Expression of EndoMT markers was measured in whole lung and endothelial cell mRNA. Sorted lung endothelial cells (from room air- and hyperoxia-exposed lungs) were subjected to bulk RNA-Seq. We show that exposure of the neonatal lung to hyperoxia leads to upregulation of key markers of EndoMT. Furthermore, using lung sc-RNA-Seq data from neonatal lung we were able to show that all endothelial cell subpopulations including the lung capillary endothelial cells show upregulation of EndoMT-related genes. Markers related to EndoMT are upregulated in the neonatal lung upon exposure to hyperoxia and show sex-specific differences. Mechanisms mediating EndoMT in the injured neonatal lung can modulate the response of the neonatal lung to hyperoxic injury and need further investigation.NEW & NOTEWORTHY We show that neonatal hyperoxia exposure increased EndoMT markers in the lung endothelial cells and this biological process exhibits sex-specific differences.

Description of reinfection of joint prosthesis after 2-stage replacement (infection of the 2nd stage prosthesis): A multicenter study.

INTRODUCTION: Two-stage exchange is the gold standard in the surgical management of prosthetic joint infection (PJI). However, perioperative reinfections (RePJI) can occur to newly inserted prosthesis, which highlights the importance of an adequate antibiotic prophylaxis, although there is scarce evidence in this field. Our objective was to evaluate the characteristics of RePJI, its prognosis and the antibiotic prophylaxis that is commonly used in second-stage surgery. METHODS: Multicentric retrospective observational study in Spanish hospitals including patients with RePJI between 2009 and 2018. RESULTS: We included 92 patients with RePJI from 12 hospitals. The most frequent isolated microorganism was Staphylococcus epidermidis in 35 cases (38.5%); 61.1% of staphylococci were methiciliin-resistant. In 12 cases (13%), the same microoganism causing the primary PJI was isolated in RePJI. When comparing with the microbiology of primary PJI, there were more cases caused by Gram-negative bacteria (the most frequent was Pseudomonas spp.) and less by Gram-positive bacteria. Failure occured in 69 cases (75%). There were 43 different courses of antibiotic prophylaxis after the second-stage surgery; the most frequent was a unique preoperative cefazolin dose, but most patients received prophylaxis before and after the second-stage surgery (61 cases). CONCLUSIONS: The most frequent microorganisms in RePJI are coagulase-negative staphylococci, although Gram-negative bacteria, especially Pseudomonas spp. are also common. There is a significant heterogeneity in antibiotic prophylaxis for a second-stage surgery. ReIPJI treatment has a high failure rate.

Microbial Degradation of Free and Halogenated Estrogens in River Water-Sediment Microcosms.

Halogenated estrogens are formed during chlorine-based wastewater disinfection and have been detected in wastewater treatment plant effluent; however, very little is known about their susceptibility to biodegradation in natural waters. To better understand the biodegradation of free and halogenated estrogens in a large river under environmentally relevant conditions, we measured estrogen kinetics in aerobic microcosms containing water and sediment from the Willamette River (OR, USA) at two concentrations (50 and 1250 ng L-1). Control microcosms were used to characterize losses due to sorption and other abiotic processes, and microbial dynamics were monitored using 16S rRNA gene sequencing and ATP. We found that estrogen biodegradation occurred on timescales of hours to days and that in river water spiked at 50 ng L-1 half-lives were significantly shorter for 17ß-estradiol (t1/2,bio = 42 ± 3 h) compared to its monobromo (t1/2,bio = 49 ± 5 h), dibromo (t1/2,bio = 88 ± 12 h), and dichloro (t1/2,bio = 98 ± 16 h) forms. Biodegradation was also faster in microcosms with high initial estrogen concentrations as well as those containing sediment. Free and halogenated estrone were important transformation products in both abiotic and biotic microcosms. Taken together, our findings suggest that biodegradation is a key process for removing free estrogens from surface waters but likely plays a much smaller role for the more highly photolabile halogenated forms.

Loss of growth differentiation factor 15 exacerbates lung injury in neonatal mice.

Growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor-ß (TGF-ß) superfamily, and its expression increases under various stress conditions, including inflammation, hyperoxia, and senescence. GDF15 expression is increased in neonatal murine bronchopulmonary dysplasia (BPD) models, and GDF15 loss exacerbates oxidative stress and decreases cellular viability in vitro. Our overall hypothesis is that the loss of GDF15 will exacerbate hyperoxic lung injury in the neonatal lung in vivo. We exposed neonatal Gdf15-/- mice and wild-type (WT) controls on a similar background to room air or hyperoxia (95% [Formula: see text]) for 5 days after birth. The mice were euthanized on postnatal day 21 (PND 21). Gdf15-/- mice had higher mortality and lower body weight than WT mice after exposure to hyperoxia. Hyperoxia exposure adversely impacted alveolarization and lung vascular development, with a greater impact in Gdf15-/- mice. Interestingly, Gdf15-/- mice showed lower macrophage count in the lungs compared with WT mice both under room air and after exposure to hyperoxia. Analysis of the lung transcriptome revealed marked divergence in gene expression and enriched biological pathways in WT and Gdf15-/- mice and differed markedly by biological sex. Notably, pathways related to macrophage activation and myeloid cell homeostasis were negatively enriched in Gdf15-/- mice. Loss of Gdf15 exacerbates mortality, lung injury, and the phenotype of the arrest of alveolarization in the developing lung with loss of female-sex advantage in Gdf15-/- mice.NEW & NOTEWORTHY We show for the first time that loss of Gdf15 exacerbates mortality, lung injury, and the phenotype of the arrest of alveolarization in the developing lung with loss of female-sex advantage in Gdf15-/- mice. We also highlight the distinct pulmonary transcriptomic response in the Gdf15-/- lung including pathways related to macrophage recruitment and activation.

Remarkable sex-specific differences at single-cell resolution in neonatal hyperoxic lung injury.

Exposure to supraphysiological concentrations of oxygen (hyperoxia) predisposes to bronchopulmonary dysplasia (BPD), which is characterized by abnormal alveolarization and pulmonary vascular development, in preterm neonates. Neonatal hyperoxia exposure is used to recapitulate the phenotype of human BPD in murine models. Male sex is considered an independent predictor for the development of BPD, but the main mechanisms underlying sexually dimorphic outcomes are unknown. Our objective was to investigate sex-specific and cell-type specific transcriptional changes that drive injury in the neonatal lung exposed to hyperoxia at single-cell resolution and delineate the changes in cell-cell communication networks in the developing lung. We used single-cell RNA sequencing (scRNAseq) to generate transcriptional profiles of >35,000 cells isolated from the lungs of neonatal male and female C57BL/6 mice exposed to 95% [Formula: see text] between PND1-5 (saccular stage of lung development) or normoxia and euthanized at PND7 (alveolar stage of lung development). ScRNAseq identified 22 cell clusters with distinct populations of endothelial, epithelial, mesenchymal, and immune cells. Our data identified that the distal lung vascular endothelium (composed of aerocytes and general capillary endothelial cells) is exquisitely sensitive to hyperoxia exposure with the emergence of an intermediate capillary endothelial population with both general capillaries (gCap) and aerocytes or alveolar capillaries (aCap) markers. We also identified a myeloid-derived suppressor cell population from the lung neutrophils. Sex-specific differences were evident in all lung cell subpopulations but were striking among the lung immune cells. Finally, we identified that the specific intercellular communication networks and the ligand-receptor pairs that are impacted by neonatal hyperoxia exposure.

Modulation of recovery from neonatal hyperoxic lung injury by sex as a biological variable.

Recovery from lung injury during the neonatal period requires the orchestration of many biological pathways. The modulation of such pathways can drive the developing lung towards proper repair or persistent maldevelopment that can lead to a disease phenotype. Sex as a biological variable can regulate these pathways differently in the male and female lung exposed to neonatal hyperoxia. In this study, we assessed the contribution of cellular diversity in the male and female neonatal lung following injury. Our objective was to investigate sex and cell-type specific transcriptional changes that drive repair or persistent injury in the neonatal lung and delineate the alterations in the immune-endothelial cell communication networks using single cell RNA sequencing (sc-RNAseq) in a murine model of hyperoxic injury. We generated transcriptional profiles of >55,000 cells isolated from the lungs of postnatal day 1 (PND 1; pre-exposure), PND 7, and PND 21neonatal male and female C57BL/6 mice exposed to 95 % FiO2 between PND 1-5 (saccular stage of lung development). We show the presence of sex-based differences in the transcriptional states of lung endothelial and immune cells at PND 1 and PND 21. Furthermore, we demonstrate that biological sex significantly influences the response to injury, with a greater number of differentially expressed genes showing sex-specific patterns than those shared between male and female lungs. Pseudotime trajectory analysis highlighted genes needed for lung development that were altered by hyperoxia. Finally, we show intercellular communication between endothelial and immune cells at saccular and alveolar stages of lung development with sex-based biases in the crosstalk and identify novel ligand-receptor pairs. Our findings provide valuable insights into the cell diversity, transcriptional state, developmental trajectory, and cell-cell communication underlying neonatal lung injury, with implications for understanding lung development and possible therapeutic interventions while highlighting the crucial role of sex as a biological variable.

Power from Geothermal Resources as a Co-product of the Oil and Gas Industry: A Review.

The increase in the global demand for energy and fossil fuel dependency is hindering efforts to reduce greenhouse gas (GHG) emissions. Geothermal resources supplement this increase in energy demand with reduced emissions because of their availability, base-load production profile, and climatic independence. Despite these advantages, the development of geothermal energy is limited because of different reasons such as subsurface exploration risk and high upfront capital cost for drilling and facility construction. However, similarities in infrastructure and operations between the oil and gas industry and the geothermal industry can optimize expense and development when exploiting geothermal resources. Thus, in this review, we present recent advances and applications of geothermal power systems in the oil and gas industry starting from the fundamentals and basic principles of geothermal energy and the organic Rankine cycle (ORC). These applications include the use of geothermal resources via abandoned wells, active wells, and paired thermal enhanced oil recovery processes with injection for fluid heating and energy production. Abandoned wells are alternatives that reduce costs in geothermal energy-use projects. The use of geothermal resources via active wells allows the valorization of a resource, such as the production of water, which is considered a byproduct of production activities in an oilfield. The use of thermally enhanced oil recovery processes enhances the energy conditions of fluids produced in the field, improving geothermal systems with fluids at higher temperatures. Finally, an overview is presented of the challenges and opportunities of geothermal energy in the oil industry where the requirement to improve the usage of technologies, such as the ORCs, with the working fluids used in the cycles, is highlighted. Furthermore, the importance of environmental studies and use of novel tools, such as nanotechnology, to improve the efficiency of geothermal energy usage is highlighted.

Diaphragmatic Hernia Post Liver Transplant With Thrombosis of the Hepatic Artery Due to Median Arcuate Ligament Syndrome: A Case Report.

Acquired diaphragmatic hernia (ADH) is a rare complication after liver surgery in adult and pediatric patients. In the literature, a few low case series have been reported. Its incidence is estimated to be between 0.74% and 2.9%. Main descriptions of ADH concern liver resection for tumors, living donor hepatic donation in adult patients, and partial liver graft transplant in children [1,2]. We encountered a rare case of ADH in the postoperative time of a liver transplant with thrombosis of hepatic artery due to median arcuate ligament syndrome (MALS). The patient was a 65-year-old woman diagnosed with symptomatic hepatorenal polycystic disease who underwent a liver transplant with an isogroup graft from a cardiac-dead donor. During the first postoperative day, the rutinary color Doppler ultrasonography showed absent artery hepatic flow, and angiography suggested thrombosis of the hepatic artery (HA). With these findings, exploratory laparotomy was done. We performed thrombectomy and liberation of the celiac artery from the median arcuate ligament by dividing its fibers. At discharge, the liver function was normal, and Doppler showed good blood flow in the HA. At fourth postoperative month, she presented in the urgency unit with upper abdominal pain and vomiting. Radiologic and endoscopic evaluation revealed an incarcerated diaphragmatic hernia and signs of gastric ischemia. After emergency laparotomy and evaluation of the left hemithorax, we performed hernial sac reduction with recovery of gastric hypoperfusion. The diaphragmatic hernia was repaired. Diaphragmatic hernia is a rarely reported complication of liver transplant and should be considered a potential late complication [1].

Alteración del sueño y uso de pantallas en distintas etapas de cuarentena en provincias de la Patagonia argentina / Sleep disturbance and use of screens in different stages of quarantine in provinces of Patagonia argentina

Introducción: debido a la pandemia desarrollada por COVID-19, el Gobierno argentino, adoptó ­a partir del 20 de marzo de 2020­ medidas excepcionales de aislamiento social, preventivo y obligatorio (ASPO) o cuarentena, con el fin de proteger la salud pública. En esta etapa se manifestó un mayor uso de pantallas que, en exceso, constituye un factor de riesgo de enfermedades cardiovasculares y alteración en la calidad del sueño. El objetivo de estudio fue estimar el cambio de las horas de sueño y de uso de pantallas antes del inicio del ASPO, en comparación con la tercera y octava semana de cuarentena en personas de 13 a 80 años de la provincia del Neuquén y el Alto Valle Río Negro-Neuquén. Métodos: se realizaron dos Encuestas, en la tercera y octava semana de cuarentena, sobre conductas y hábitos de vida en personas entre 13-80 años. Fueron autoadministradas y enviadas por redes sociales. El muestreo fue aleatorio. Los datos se analizaron usando el paquete estadístico SPSS®. Las encuestas fueron anónimas y confidenciales. Resultados: se obtuvieron 3386 respuestas. De ellas se infirió que la cantidad de horas diarias frente a pantallas y las horas de sueño y el inicio del sueño fueron diferentes por grupos en los períodos precuarentena, y tercera y octava semana de la cuarentena. El grupo de adolescentes mostró mayores diferencias en todas las variables respecto del período precuarentena. La correlación entre las horas de pantalla y las horas de sueño fue baja, en las 3 etapas de la cuarentena. Conclusión: este estudio estimó el cambio de hábitos durante la cuarentena. En ese período se observó mayor cantidad de horas de sueño, un retraso en el tiempo de inicio del sueño y más horas frente a las pantallas; estas diferencias fueron significativas respecto del período precuarentena, y las mayores diferencias se registraron entre los adolescentes. (AU)

Introduction: due to the pandemic developed by COVID 19, the Argentine Government adopted, as of March 20, 2020, exceptional measures of social, preventive and mandatory isolation (ASPO) or quarantine in order to protect public health. In this stage, there was a greater use of screens that in excess, constitutes a risk factor for cardiovascular diseases and alteration in the quality of sleep. Methods: two Surveys were conducted, in the third and eighth week of quarantine, on behaviors and life habits in people between 13-80 years of age. They were self-administered and sent through social networks. The sampling was random. The data were analyzed using the SPSS® statistical package. The surveys were anonymous and confidential. Results: 3386 responses were obtained. It was obtained that the amount of daily hours in front of screens and the hours of sleep and the onset of sleep were different by groups of pre, third and eighth week of quarantine. The adolescent groups howed greater differences in all variables with respect to the pre-quarantine period. The correlation between the hours of screen and the hours of sleep was low, in the 3 stages of quarantine. Conclusion: this study estimated the change in habits during quarantine. In quarantine, longer hours of sleep, a delay in the time of onset of sleep and more hours in front of screens were observed, these differences being significant with respect to the pre-quarantine period, with the greatest differences being established in adolescents. (AU)

Guselkumab as a switching strategy after anti-TNFα, anti-IL17, or anti-IL12/23 therapies in moderate-to-severe psoriasis.

The IL23/Th17 axis plays a strategic role in psoriasis (PSO). Guselkumab (GUS) is a selective inhibitor of the IL23p19 subunit. Its introduction has managed to increase the levels of efficacy, safety and survival in PSO. In real clinical practice, patients can loss effectiveness or suffered adverse events that forces a change in their treatments. There is scarce evidence of the effectiveness, safety, and survival of GUS in real clinical practice after anti-TNFα, anti-IL17, and/or anti-IL12/23. This is multicenter, observational and retrospective study of real clinical practice includes patients with moderate-to-severe plaque PSO in treatment with GUS. The objective of the study was to evaluate the effectiveness of GUS after anti-TNFα, anti-IL17, and anti-IL12/23. The study includes clinical information from February 2019 to February 2022. PASI, BSA, Pruritus, DLQI, survival, and safety were evaluated up to 76 weeks. Analyses were performed "as observed" using GraphPad Prism version 8.3.0 for Windows. A total of 103 patients were included in the analysis. At baseline there were significant differences between the anti-TNF, anti-IL17, and anti-IL12/23 groups for (1) dyslipidemia; (2) number of previous biological treatments and (3) PASI, BSA, VAS Pruritus, and DLQI scores. The effectiveness of GUS in terms of PASI, BSA, Pruritus, and DLQI was not impacted by previous biological alternatives. Treatment survival including discontinuations due to lack of effectiveness or safety reasons was 100%, 92.7%, and 92.1% for anti-TNFα, anti-IL17, and anti-IL12/23, respectively, at 130 weeks. No differences were found between groups. One adverse event was reported in the anti-LI12/23 group. The mid-term effectiveness, safety and survival of GUS if not impacted by previous biological therapy as anti-TNFα, anti-IL17, and/or anti-IL12/23. Our results indicate that GUS could be a switching strategy in patients who fail or present AE to other biological alternatives in moderate-to-severe PSO.

Potential protective effect of beta-caryophyllene against cadmium chloride-induced damage to the male reproductive system in mouse.

Cadmium is a metal that can affect the male reproductive process, possibly leading to infertility. In contrast, beta-caryophyllene (BC) is a sesquiterpene that has shown antigenotoxic, anticancer, and antioxidant properties. Therefore, the aim of the present study was to determine the protective effect of BC against the deleterious effects of cadmium chloride (CC) on various mouse testicular and sperm parameters. We tested three doses of BC (20, 200, and 400 mg/kg) given before and during exposure to 3 mg/kg CC (six days after a single administration). Our results show significant alleviation of the damage induced by CC after the three doses of BC. Regarding the sperm concentration and morphology, the protection with the high dose was complete, and regarding sperm mobility and viability, the protection was more than 74%. In the comet assay, the highest dose showed a reduction of 92.5% in the damage induced by CC, and regarding the number of micronuclei in the spermatids, the reduction was 83.3%. In the oxidative evaluation, regarding sperm lipoperoxidation, the improvement was complete with the high dose, and in the ABTS.+ test, the improvement in the response to the BC high dose was 26.3%. Regarding testicular lipoperoxidation and protein oxidation, the protective effects of the high BC dose were 87.6% and 89.9%, respectively. We also found that BC protected against the histological and morphometric alterations induced by CC. Therefore, our study clearly demonstrates the beneficial, chemopreventive effect of BC against the mouse sperm and testicular alterations induced by CC.

Aplicaciones e implicaciones de la pausa al final de la inspiración en ventilación mecánica / Applications and implications of end-inspiratory pause in mechanical ventilation / Aplicações e implicações da pausa ao final da inspiração na ventilação mecânica

Resumen: El uso de la pausa al final de la inspiración (PFI) en ventilación mecánica data de hace más de 50 años y con mayor impulso en la década de los 70, se le atribuye una mejoría en la presión parcial de oxígeno arterial (PaO2) al incrementar la presión media de la vía aérea (Pma), mayor aclaramiento de la presión parcial de dióxido de carbono arterial (PaCO2) y permite la monitorización de la presión meseta (Pmeseta) en la mecánica ventilatoria; sin embargo, los estudios clínicos sobre su uso son escasos y controversiales. En este artículo se abordan los mecanismos fisiológicos, fisiopatológicos y la evidencia sobre el uso de la PFI en ventilación mecánica (VM).

Abstract: The use of the end inspiratory pause (EIP) in mechanical ventilation has been going on for more than 50 years and with greater momentum in the 1970s, an improvement in the partial pressure of arterial oxygen (PaO2) is attributed to the increase mean airway pressure, greater clearance of partial pressure of arterial carbon dioxide and allows monitoring of plateau pressure in ventilatory mechanics; However, the Clinical studies on its use are few and controversial. This article addresses the physiological and pathophysiological mechanisms and the evidence on the use of EIP in mechanical ventilation.

Resumo: A utilização da pausa ao final da inspiração (PFI) na ventilação mecânica remonta a mais de 50 anos e com maior impulso na década de 70, atribui-se uma melhora na pressão parcial de oxigênio arterial (PaO2) pelo aumento da pressão média das vias aéreas (Pma), uma maior depuração da pressão parcial de dióxido de carbono arterial (PaCO2) e permite a monitorização da pressão de platô (Pplateau) na mecânica ventilatória, porém estudos Os dados clínicos sobre seu uso são escassos e controversos. Este artigo aborda os mecanismos fisiológicos e fisiopatológicos e as evidências sobre o uso do PFI na ventilação mecânica (VM).

Ultrasonido Point-Of-Care (POCUS) durante la reanimación cardiopulmonar para el diagnóstico de causas reversibles de arresto cardiaco / Point-Of-Care ultrasound (POCUS) during cardiopulmonary resuscitation for the diagnosis of reversible causes of cardiac arrest / Ultrassonografia Point-of-Care (POCUS) durante a reanimação cardiopulmonar para o diagnóstico de causas reversíveis de parada cardíaca

Resumen: La ultrasonografía enfocada al paciente crítico o «ultrasonido Point-Of-Care¼ (POCUS) es una herramienta utilizada en la cabecera del paciente en distintas áreas de la medicina crítica y servicios de emergencias debido a su practicidad y a que provee gran información de forma rápida y no invasiva para realizar diagnósticos y abordajes terapéuticos. El arresto cardiaco (AC) es una situación crítica que requiere una adecuada reanimación cardiopulmonar (RCP) y en la que es crucial la identificación de la etiología para realizar una intervención rápida y lograr la resolución de la misma, particularmente en el escenario de una actividad eléctrica sin pulso (AESP) en la que la ecografía cobra vital importancia. La implementación de protocolos de reanimación cardiopulmonar apoyados de un abordaje ultrasonográfico es factible y de gran utilidad para la identificación etiológica del AC y la resolución de causas específicas.

Abstract: Ultrasound focused on the critical patient or «Point-Of-Care ultrasound¼ (POCUS) is a tool used at the patient's bedside in different areas of critical medicine and emergency services due to its practicality as it provides great information quickly and non-invasive for diagnostic and therapeutic approaches. Cardiac arrest (CA) is a critical situation that requires adequate cardiopulmonary resuscitation (CPR), and in which the identification of the etiology is crucial to carry out a rapid intervention and achieve its resolution, particularly in the setting of a pulseless electrical activity (AESP) in which ultrasound is of vital importance. The implementation of cardiopulmonary resuscitation protocols supported by an ultrasound approach is feasible and of great utility for the etiological identification of CA and the resolution of specific causes.

Resumo: A ultrassonografia focada em pacientes críticos ou «Point-Of-Care ultra-som¼ (POCUS) é uma ferramenta utilizada à beira do leito do paciente em diferentes áreas da medicina crítica e serviços de emergência devido à sua praticidade e ao fato de fornecer uma grande quantidade de informações rapidamente e não invasivo para abordagens diagnósticas e terapêuticas. A parada cardíaca (PC) é uma situação crítica que requer uma adequada ressuscitação cardiopulmonar (RCP) e na qual a identificação da etiologia é crucial para a rápida intervenção e resolução, particularmente no cenário de uma atividade elétrica sem pulso (AESP) em qual o ultra-som é de vital importância. A implementação de protocolos de ressuscitação cardiopulmonar apoiados por uma abordagem ultrassonográfica é viável e muito útil para a identificação etiológica do RAC e resolução de causas específicas.