HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.

Mechanisms of Electrical Switching of Ultrathin CoO/Pt Bilayers.

We study current-induced switching of the Néel vector in CoO/Pt bilayers to understand the underlying antiferromagnetic switching mechanism. Surprisingly, we find that for ultrathin CoO/Pt bilayers electrical pulses along the same path can lead to an increase or decrease of the spin Hall magnetoresistance signal, depending on the current density of the pulse. By comparing these results to XMLD-PEEM imaging of the antiferromagnetic domain structure before and after the application of current pulses, we reveal the details of the reorientation of the Néel vector in ultrathin CoO(4 nm). This allows us to understand how opposite resistance changes can result from a thermomagnetoelastic switching mechanism. Importantly, our spatially resolved imaging shows that regions where the current pulses are applied and regions further away exhibit different switched spin structures, which can be explained by a spin-orbit torque-based switching mechanism that can dominate in very thin films.

Area Socioeconomic Status is Associated with Refusal of Recommended Surgery in Patients with Metastatic Bone and Joint Disease.

BACKGROUND: This study sought to identify associations between the Yost Index, a geocoded area neighborhood socioeconomic status (nSES) score, and race/ethnicity with patient refusal of recommended surgery for metastatic bone disease. METHODS: Patients with metastatic bone disease were extracted from the Surveillance, Epidemiology, and End Results database. The Yost Index was geocoded using factor analysis and categorized into quintiles using census tract-level American Community Service (ACS) 5-year estimates and seven nSES measures. Multivariable logistic regression models calculated odds ratios (ORs) of refusal of recommended surgery and 95% confidence intervals (CIs), adjusting for clinical covariates. RESULTS: A total of 138,257 patients were included, of which 14,943 (10.8%) were recommended for surgical resection. Patients in the lowest nSES quintile had 57% higher odds of refusing surgical treatment than those in the highest quintile (aOR = 1.57, 95% CI 1.30-1.91, p < 0.001). Patients in the lowest nSES quintile also had a 31.2% higher age-adjusted incidence rate of not being recommended for surgery compared with those in the highest quintile (186.4 vs. 142.1 per 1 million, p < 0.001). Black patients had 34% higher odds of refusing treatment compared with White patients (aOR = 1.34, 95% CI 1.14-1.58, p = 0.003). Advanced age, unmarried status, and patients with aggressive cancer subtypes were associated with higher odds of refusing surgery (p < 0.001). CONCLUSIONS: nSES and race/ethnicity are independent predictors of a patient refusing surgery for metastatic cancer to bone, even after adjusting for various clinical covariates. Effective strategies for addressing these inequalities and improving the access and quality of care of patients with a lower nSES and minority backgrounds are needed.

Multidisciplinary surgical considerations for en bloc resection of sacral chordoma: review of recent advances and a contemporary single-center series.

OBJECTIVE: Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors' institutional case series. METHODS: The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed. RESULTS: The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision. CONCLUSIONS: The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.

REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial.

BACKGROUND: Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST. METHODS: Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment. RESULTS: From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST. CONCLUSIONS: Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02638766.

Angiostrongylus cantonensis Infection in Brown Rats (Rattus norvegicus), Atlanta, Georgia, USA, 2019-2022.

Rat lungworm (Angiostrongylus cantonensis), a zoonotic parasite invasive to the United States, causes eosinophilic meningoencephalitis. A. cantonensis harbors in rat reservoir hosts and is transmitted through gastropods and other paratenic hosts. We discuss the public health relevance of autochthonous A. cantonensis cases in brown rats (Rattus norvegicus) in Atlanta, Georgia, USA.

Clinical impact of time to results from the microbiology laboratory in bloodstream infections caused by carbapenemase-producing Enterobacterales (TIME-CPE STUDY).

OBJECTIVES: To evaluate the impact of time to results (TTR) on the outcome of patients with carbapenemase-producing Enterobacterales bloodstream infections (CPE-BSI). METHODS: Times-series study conducted from January 2014 to December 2021, selecting patients with first CPE-BSI episodes. Periods of intervention were defined according to implementation of diagnostic bundle tests in the microbiology laboratory: pre-intervention (January 2014-December 2017) and post-intervention (January 2018-December 2021). TTR was defined as time elapsed from positivity time of the blood culture bottles to physicians' notification of CPE-BSI episodes, and was evaluated in patients who received inappropriate empirical and switched to appropriate targeted treatment (switch group). Analysis of a composite unfavourable outcome (mortality at Day 30 and/or persistent and/or recurrent bacteraemia) was performed for the total episodes and in the switch group. RESULTS: One hundred and nine episodes were analysed: 66 pre-intervention and 43 post-intervention. Compared with pre-intervention, patients in the post-intervention period were younger (68 versus 63 years, P = 0.04), had INCREMENT score > 7 (31.8% versus 53.5%, P = 0.02) and unfavourable outcome (37.9% versus 20.9%, P = 0.04). Proportion of TTR > 30 h was more frequent pre-intervention than post-intervention (61.7% versus 35.5%, P = 0.02). In multivariate analysis of the 109 episodes, source other than urinary or biliary (OR 2.76, 95% CI 1.11-6.86) was associated with unfavourable outcome, while targeted appropriate treatment trended to being protective (OR 0.17, 95% CI 0.03-1.00). Considering the switch group (n = 78), source other than urinary or biliary (OR 14.9, 95% CI 3.25-69.05) and TTR > 30 h (OR 4.72, 95% CI 1.29-17.22) were associated with unfavourable outcome. CONCLUSIONS: Decreased TTR in the post-intervention period was associated with the outcome in patients with CPE-BSI episodes.

Imaging score for differentiation of meningioma grade.

PURPOSE: We sought to establish a comprehensive imaging score indicating the likelihood of higher WHO grade meningiomas pre-operatively. METHODS: All surgical intracranial meningioma patients at our institution between 2014 and 2018 underwent retrospective chart review. Preoperative MRI sequences were reviewed, and imaging features were included in the score based on statistical and clinical significance. Point values for each significant feature were assigned based on the beta coefficients obtained from multivariate analysis. The imaging score was calculated by adding up the points, for a total score of 0 to 5. The predictive ability of the score to identify higher-grade meningiomas was evaluated. RESULTS: Ninety patients, 50% of whom had a postoperative diagnosis of WHO grade II meningioma, were included. The mean age for the population was 59.9 years and 70% were female. Tumor volume ≥ 36.0 cc was assigned 2 points, presence of irregular tumor borders was assigned 2 points, and presence of peritumoral edema was assigned 1 point. The probability of having a WHO grade II meningioma was 0% with a score of 0, 25.0% with a score of 1, 38.5% with a score of 2, 65.4% with a score of 3, and 83.3% with a score of 4 or greater. A threshold of ≥ 3 points achieved a recall of 0.80, precision of 0.73, F1-score of 0.77, accuracy of 0.76, and AUC of 0.82. CONCLUSION: The proposed imaging scoring system had good predictive capability for WHO grade II meningiomas with good discrimination and calibration. External validation is needed.

Association of air pollution with olfactory identification performance of São Paulo residents: a cross-sectional study.

OBJECTIVE: Exposure to particulate matter of 10 µm or less in diameter (PM10) has been implicated in pulmonary and cardiovascular diseases. However, the effect of PM10 on olfaction has not been well established. We estimated individual acute and chronic PM10 exposure levels in a large Brazilian cohort and related them to the ability to identify odors. METHODS: Adults from São Paulo (n = 1358) were recruited from areas with different levels of air pollution. To verify individual exposure to air pollution, the averages of 30, 60, 90, 180 and 364 days of PM10 were interpolated to subjects' zip codes using the kriging method. Olfactory identification performance was tested using the University of Pennsylvania Smell Identification Test (UPSIT®). Multiple linear regressions were used to calculate the effect of air pollution on olfactory identification performance, controlling for demographic and other variables that affect the sense of smell. RESULTS: Acute exposures to PM10 were related to worse UPSIT® scores, including 30- (ß = - 0.94, 95% Confidence Interval [CI] - 0.98, - 0.89), 60- (ß = - 1.09, 95% CI = - 1.13, - 1.04) and 90-day intervals (ß = - 1.06, 95% CI - 1.10, - 1.02) (reference for ß: 1 µm/m3 increase in PM10 exposure per point decrease in UPSIT® score). Chronic exposures were also associated with worse olfaction for both 180- (ß = - 1.06, 95% CI - 1.10, - 1.03) and 364-day (ß = - 0.87, 95% CI - 0.90, - 0.84) intervals. As in prior work, men, older, low-income, and low-schooling people demonstrated worse olfactory performance. CONCLUSION: Acute and chronic exposure to PM10 is strongly associated with olfactory identification performance in Brazilian adults. Understanding the mechanisms which underlie these relationships could help to improve chemosensory function with a large public health impact.

Performance assessment and external validation of specific thresholds of total psoas muscle cross-sectional area as predictors of mortality in oncologic spine surgery for spinal metastases.

PURPOSE: The purpose of this study was to assess the utility of low muscle mass (LMM) in predicting 90-day and 12-month mortality after spinal tumor surgery. METHODS: We identified 115 patients operated on for spinal metastases between April 2012 and August 2022 who had available perioperative abdominal or lumbar spine CT scans and minimum 90-day follow-up. LMM was defined as a total psoas muscle cross-sectional area (TPA) at the L4 pedicle level less than 10.5 cm2 for men and less than 7.2 cm2 for women based on previously reported thresholds. A secondary analysis was performed by analyzing TPA as a continuous variable. The primary endpoint was 90-day mortality, and the secondary endpoint was 12-month mortality. Multivariate logistic regression analyses were performed. RESULTS: The 90-day mortality was 19% for patients without and 42% for patients with LMM (p = 0.010). After multivariate analysis, LMM was not independently associated with increased odds of 90-day mortality (odds ratio 2.16 [95% confidence interval 0.62 to 7.50]; p = 0.223). The 12-month mortality was 45% for patients without and 71% for patients with LMM (p = 0.024). After multivariate analysis, LMM was not independently associated with increased odds of 12-month mortality (OR 1.64 [95% CI 0.46 to 5.86]; p = 0.442). The secondary analysis showed no independent association between TPA and 90-day or 12-month mortality. CONCLUSION: Patients with LMM had higher rates of 90-day and 12-month mortality in our study, but this was not independent of other parameters such as performance status, hypoalbuminemia, or primary cancer type.

The prognostic nutritional index (PNI) is independently associated with 90-day and 12-month mortality after metastatic spinal tumor surgery.

INTRODUCTION: Estimated postoperative survival is an important consideration during the decision-making process for patients with spinal metastases. Nutritional status has been associated with poor outcomes and limited survival in the general cancer population. The objective of this study was to evaluate the predictive utility of the prognostic nutritional index (PNI) for postoperative mortality after spinal metastasis surgery. METHODS: A total of 139 patients who underwent oncologic surgery for spinal metastases between April 2012 and August 2022 and had a minimum 90-day follow-up were included. PNI was calculated using preoperative serum albumin and total lymphocyte count, with PNI < 40 defined as low. The mean PNI of our cohort was 43 (standard deviation: 7.7). The primary endpoint was 90-day mortality, and the secondary endpoint was 12-month mortality. Multivariate logistic regression analyses were performed. RESULTS: The 90-day mortality was 27% (37/139), and the 12-month mortality was 56% (51/91). After controlling for age, ECOG performance status, total psoas muscle cross-sectional area (TPA), and primary cancer site, the PNI was associated with 90-day mortality [odds ratio 0.86 (95% confidence interval 0.79-0.94); p = 0.001]. After controlling for ECOG performance status and primary cancer site, the PNI was associated with 12-month mortality [OR 0.89 (95% CI 0.82-0.97); p = 0.008]. Patients with a low PNI had a 50% mortality rate at 90 days and an 84% mortality rate at 12 months. CONCLUSION: The PNI was independently associated with 90-day and 12-month mortality after metastatic spinal tumor surgery, independent of performance status, TPA, and primary cancer site.

Are There Racial or Socioeconomic Disparities in Ambulatory Outcome or Survival After Oncologic Spine Surgery for Metastatic Cancer? Results From a Medically Underserved Center.

BACKGROUND: Disparities among patients with cancer are well documented. Recent studies suggest these disparities also affect patients undergoing metastatic spinal tumor surgery. However, it is unclear whether social factors are associated with ambulatory outcomes or overall survival. QUESTIONS/PURPOSES: In patients undergoing metastatic spinal tumor surgery, (1) Are race, Social Vulnerability Index (SVI) score, or insurance status associated with a lower likelihood of postoperative ambulation? (2) Are race, SVI score, or insurance status associated with shorter overall survival? METHODS: Between April 2012 and June 2021, we surgically treated 148 patients for metastatic cord compression or spinal mechanical instability because of cancer. Inclusion criteria were patients with complete demographic, social, oncologic, and follow-up data and patients who were followed until death or for at least 3 months postoperatively. Based on these criteria, 12% (18 of 148) were excluded because they had incomplete data and another 7% (11 of 148) were excluded because they were lost before the minimum study follow-up interval, leaving 80% (119) for analysis. Collected social data included self-reported race (White, Black, Hispanic or Latino, or other), SVI score, and primary insurance (Medicare, Medicaid, or private). The median age of the group was 62 years (interquartile range [IQR] 53 to 70 years), and 58% of patients were men (69 of 119). The race distribution was 45% Black (54 of 119), 32% Hispanic or Latino (38 of 119), 16% White (19 of 119), and 7% other (eight of 119). The median SVI score was 89.8 (IQR 73.8 to 98.5), and 74% of patients (88) were categorized as having high vulnerability. The insurance distribution was as follows: Medicare: 43%, Medicaid: 36%, and private insurance: 21%. The primary outcome variable was complete inability to ambulate postoperatively and the secondary outcome was median overall survival. Exploratory data analysis, univariate and multivariate logistic regression, and univariate and multivariate Cox regression analyses were performed. RESULTS: After controlling for race, SVI score, insurance status, primary cancer, and modified Bauer score, the only factor independently associated with postoperative nonambulation was preoperative nonambulatory status (odds ratio 59.3 [95% confidence interval (CI) 13.2 to 266.1]; p < 0.001). After controlling for variables such as performance status, BMI, primary cancer, modified Bauer score, and insurance status, factors independently associated with survival included Eastern Cooperative Oncology Group performance status (hazard ratio [HR] 1.4 [95% CI 1.1 to 2.0]; p = 0.03), prostate cancer (HR 0.4 [95% CI 0.1 to 0.9]; p = 0.03), and hematologic cancer (HR 0.3 [95% CI 0.1 to 0.8]; p = 0.02). Race, SVI score, and insurance status were not associated with overall survival. CONCLUSION: In this study, we found no difference in ambulatory outcome for patients based on their race, SVI score, or insurance status. Likewise, no differences in postoperative survival were found. These findings suggest that despite differences in presentation or short-term outcome reported in other investigations, the social factors we explored were not associated with the likelihood of a patient being nonambulatory postoperatively or shorter survival after spinal tumor surgery. Research studies that analyze race as a covariate of interest should take care to explore metrics of socioeconomic deprivation (such as the SVI score) to avoid drawing misleading conclusions. LEVEL OF EVIDENCE: Level III, therapeutic study.

First record of the parasitoid wasp Ixodiphagus hookeri (Hymenoptera: Encyrtidae) infesting the tick Amblyomma nodosum (Acari: Ixodidae).

Ticks (Ixodida) are ecologically important ectoparasites that may impact human health and economic activities. Parasitoid wasps are natural enemies of ticks and a potential option for its biological control. In the present study, we recorded parasitism of the nymphs of the tick Amblyomma nodosum by the parasitoid wasp Ixodiphagus hookeri. The ticks, in turn, were parasitizing white-bearded manakins, Manacus manacus (Passeriformes: Pipridae) in the União Biological Reserve, one of the last major remnants of lowland rainforest in Rio de Janeiro state, southeastern Brazil. During the collection of ectoparasites from two manakins in this reserve, 20-30 parasitoid wasps hatched spontaneously from two of the ticks collected. The species of the tick nymphs and adult wasps were identified using morphological traits and molecular analyses. This record is the first documented case of I. hookeri parasitizing A. nodosum and the first time that parasitoid wasps have been found in ticks parasitizing birds in Brazil. This is also the first record of Ixodiphagus from southeastern Brazil in more than a century, with the only other record dating back to 1914. The record presented here provides valuable new information on the biology of this tick and its parasitoids, and new insights into this interspecific interaction. Further research on these vertebrate-tick-wasp interactions will be necessary to better understand the respective roles of the organisms involved in these processes.

COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital.

Introduction: Our work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. Methods: Retrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48 h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. Results: Two-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p < 0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4-16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1-5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2-5.1, p < 0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p < 0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13). Conclusions: Superinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.

Introducción: Nuestro trabajo describe la frecuencia de sobreinfecciones en pacientes con COVID-19 en UCI e identifica factores de riesgo asociados con su aparición. Secundariamente, evaluamos la estancia en UCI, mortalidad intrahospitalaria y analizamos un subgrupo de infecciones causadas por microorganismos multirresistentes (MDR). Métodos: Estudio realizado entre marzo y junio de 2020. Definimos como sobreinfección a aquellas que aparecieron ≥48 h del ingreso. Incluimos las causadas por bacterias y hongos y evaluamos la infección respiratoria asociada a la ventilación mecánica (IRAVM), bacteriemia primaria, bacteriemia secundaria e infección del tracto urinario. Se realizó un análisis multivariante de los factores de riesgo. Resultados: Incluimos 213 pacientes, documentándose 174 episodios de sobreinfección en 95 casos (44,6%): IRAVM 78 episodios, bacteriemia primaria 66, bacteriemia secundaria 9 e ITU 21. Los MDR causaron el 29,3% de los episodios. La mediana de tiempo hasta el primer episodio fue de 18 días, siendo mayor en las causadas por MDR vs. no MDR (28 vs. 16, p < 0,01). El análisis multivariante identificó la administración de corticoides (OR 4,9 IC 95% 1,4-16,9), tocilizumab (OR 2,4 IC 95% 1,1-5,9) y antibióticos de amplio espectro (OR 2,5 IC 95% 1,2-5,1) como factores de riesgo asociados. Los pacientes con sobreinfección presentaron una estancia en UCI más prolongada (35 vs. 12 días, p < 0,01) pero no mayor mortalidad intrahospitalaria (45,3% vs. 39,7%, p 0,13). Conclusiones: Las sobreinfecciones en los pacientes con COVID-19 aparecen tardíamente. La administración de corticoides, tocilizumab y antibióticos de amplio espectro se asocia con su aparición.

Biochemical composition and adenylate energy charge shifts in longfin yellowtail (Seriola rivoliana) embryos during development under different temperatures.

The longfin yellowtail Seriola rivoliana is an emerging species for aquaculture diversification worldwide and production relies on fertilized eggs from captive broodstock. Temperature is the main factor that influences the developmental process and success during fish ontogeny. However, the effects of temperature on the utilization of the main biochemical reserves and bioenergetics are scarcely investigated in fish, whereas protein, lipid and carbohydrate metabolism have critical roles in maintaining cellular energy homeostasis. In this context, we aimed to evaluate metabolic fuels (protein, lipids, triacylglicerides, carbohydrates), adenylic nucleotides and derivates (ATP, ADP, AMP, IMP), and the adenylate energy charge (AEC) during embryogenesis and in hatched larvae in S. rivoliana at different temperatures. For this purpose, fertilized eggs were incubated at six constant (20, 22, 24, 26, 28 and 30 °C) and two oscillating (21⇄29 °C) temperatures. Biochemical analyses were made at blastula, optic vesicles, neurula, prehatch and hatch periods. Results indicated that the developmental period had a major influence on the biochemical composition at any temperature regime tested during the incubation. Protein content decreased only at hatching mainly due to the loss of the chorion, total lipids tended to increase at the neurula period and variations in carbohydrates depended on the particular spawn analyzed. Triacylglicerides were a critical egg fuel during hatching. The high AEC during embryogenesis and even in hatched larvae suggested an optimal energy balance regulation. The lack of critical biochemical changes from different temperature regimes during embryo development confirmed that this species exhibits a high adaptive capacity in response to constant and fluctuating temperatures. However, the timing of hatching was the most critical period of development, where biochemical components and energy utilization significantly changed. The oscillating temperatures tested may have physiological advantages without detrimental energetic effects that will require further research on larval quality after hatching.

NOTCH1 Gene as a Novel Cause of Thoracic Aortic Aneurysm in Patients with Tricuspid Aortic Valve: Two Cases Reported.

Thoracic aortic aneurysms (TAA) consist of abnormal dilation or the widening of a portion of the ascending aorta, due to weakness or destructuring of the walls of the vessel and are potentially lethal. The congenital bicuspid aortic valve (BAV) is considered a risk factor for the development of TAA because asymmetric blood flow through the bicuspid aortic valve detrimentally influences the wall of the ascending aorta. NOTCH1 mutations have been associated with non-syndromic TAAs as a consequence of BAV, but little is known regarding its haploinsufficiency and its relationship with connective tissue abnormalities. We report two cases in which there is clear evidence that alterations in the NOTCH1 gene are the cause of TAA in the absence of BAV. On the one hand, we describe a 117 Kb deletion that includes a large part of the NOTCH1 gene and no other coding genes, suggesting that haploinsufficiency can be considered a pathogenic mechanism for this gene associated with TAA. In addition, we describe two brothers who carry two variants, one in the NOTCH1 gene and another in the MIB1 gene, corroborating the involvement of different genes of the Notch pathway in aortic pathology.

Platinum-Based Regimens Are Active in Advanced Pediatric-Type Rhabdomyosarcoma in Adults and Depending on HMGB1 Expression.

Rhabdomyosarcoma (RMS) in adults is a rare and aggressive disease, which lacks standard therapies for relapsed or advanced disease. This retrospective study aimed to describe the activity of BOMP-EPI (bleomycin, vincristine, methotrexate and cisplatin alternating with etoposide, cisplatin and ifosfamide), an alternative platinum-based regimen, in adult patients with relapsed/metastatic RMS. In the study, 10 patients with RMS with a median age at diagnosis of 20.8 years and a female/male distribution of 6/4 received a mean of 2.5 cycles of BOMP-EPI. The best RECIST response was a complete response in 1/10 (10%) patients, a partial response in 5/10 (50%), stable disease in 3/10 (30%) and progression in 1/10 (10%). With a median follow-up in the alive patients from the start of therapy of 30.5 months (15.7-258), all patients progressed with a median progression-free survival of 8.47 months (95% CI 8.1-8.8), and 7/10 patients died with a median overall survival of 24.7 months (95% CI 13.7-35.6). BOMP-EPI was an active chemotherapy regimen in adults with pediatric-type metastatic RMS, with outcomes in terms of survival that seem superior to what was expected for this poor-prognosis population. Low HMGB1 expression level was identified as a predictive factor of better response to this treatment.

Implementation and impact of an antibiotic control program and multidrug-resistant bacterial colonization in a liver transplant unit.

INTRODUCTION: infections by multidrug-resistant bacteria are a major cause of morbidity and mortality in transplant patients. OBJECTIVE: a retrospective single-center study was performed to evaluate the implementation of an Antimicrobial Treatment Optimization Program (PROA) on multidrug-resistant bacteria colonization and infection after liver transplant (LT). METHODS: colonization by multidrug-resistant bacteria and infections during the first year after a liver transplant were analyzed in a group of 76 transplanted patients in two stages, before and after PROA (2016-2019). Clinical variables related to infection, readmissions and survival one year after the liver transplant were analyzed. RESULTS: there was good adherence to the PROA. Infection was the most frequent cause for readmission during the first year after the liver transplant. Incidence of infections was similar during both periods (mean of 1.25 and 1.5 episodes of bacterial infection per patient/year, respectively) with 19 bacterial infectious episodes, six by hospital-acquired multidrug-resistant and extensively drug-resistant (MDR-XDR) bacteria in the pre-PROA stage, and 18 bacterial infectious episodes, five by MDR-XDR in the post-PROA stage. A 37 % decrease of post-TH of rectal colonization by MDR-XDR after liver transplant was observed during 2019. CONCLUSIONS: epidemiological surveillance policies and antibiotic optimization are key to control the increase of colonization and infection by multidrug-resistant bacteria in liver transplant units. Long-term studies are needed to better evaluate the impact of these programs.

The application of the FLOTAC technique for detection of helminth eggs of medical and veterinary importance in soil samples.

The FLOTAC technique was initially developed to detected infective stages of parasites in animal and human feces. Recently, its applicability has been extended by the use in pastures and vegetables for human consumption. However, its use for the detection of parasites in the soil has never been investigated. In this study, we assessed the performance of the FLOTAC and compared with centrifugal flotation (CFT) and spontaneous sedimentation (SST) techniques. A total of 50 soil samples were collected from the Metropolitan region of Recife, Northeastern Brazil. Initially, samples were standardized, and then assessed in duplicate by the FLOTAC, CFT and SST. Cohen's kappa coefficient, sensitivity, specificity, positive and negative predictive values, and accuracy of the FLOTAC, CFT and SST were assessed using the results of the combination of all three techniques as gold standard. Out of all analyses performed, in 96% (48/50), helminth eggs of parasites were detected. In particular, 96% (48/50) of samples analysed through the FLOTAC technique, 76% (38/50) for CFT and 28% (14/50) for SST were positive. Nematode eggs of the Ancylostomatidae and Ascarididae families were those mostly detected in this study. Overall, the FLOTAC presented high values of sensitivity, demonstrating that this method may also be employed for detection of parasites in soil samples. This study opens new possibilities for the use of the FLOTAC technique, highlighting its role as a potential tool for detecting environmental contamination by parasites of medical and veterinary importance.

Vector-borne pathogens of zoonotic concern in dogs from a Quilombola community in northeastern Brazil.

Canine vector-borne pathogens (CVBPs) comprise a group of disease agents mainly transmitted by ticks, fleas, mosquitoes and sand flies. In this study, we assessed the presence of CVBPs in an Afro-descendent community (Quilombola) of northeastern, Brazil. Dog blood samples (n = 201) were collected and analyzed by rapid test for the detection of antibodies against Leishmania spp., Anaplasma spp., Ehrlichia spp. and Borrelia burgdorferi sensu lato (s.l.), and antigens of Dirofilaria immitis. In addition, polymerase chain reactions were performed for Anaplasmataceae, Babesia spp., Hepatozoon spp., Rickettsia spp. and B. burgdorferi s.l. Overall, 66.7% of the dogs scored positive to at least one pathogen at serological and/or molecular methods. Antibodies against Ehrlichia spp. were the most frequently detected (57.2%; n = 115/201), followed by Anaplasma spp. (8.5%; n = 17/201), Leishmania spp. (8.5%; n = 17/201) and B. burgdorferi s.l. (0.5%; n = 1/201). For D. immitis, 11 out of 201 (5.5%) animals scored positive. At the molecular analysis, 10.4% (n = 21/201) of the samples scored positive for Babesia spp./Hepatozoon spp., followed by Anaplasmataceae (5.0%; n = 10/201) and Rickettsia spp. (3.0%; n = 6/201). All samples were negative for B. burgdorferi s.l. Our data demonstrated the presence of CVBPs in the studied population, with a high seropositivity for Ehrlichia spp. In addition, considering the detection of zoonotic pathogens in dogs and their relationship with people from Quilombola communities, effective control strategies are advocated for minimizing the risk of infection in this socially vulnerable human population and their pets.