Within-host transition to GES-55 during a GES-6-producing Serratia marcescens outbreak: Emergence of ceftazidime-avibactam resistance and increased susceptibility to carbapenems.

OBJECTIVES: To describe the in vivo emergence of ceftazidime-avibactam resistance in GES-type carbapenemases and to characterize an unusual outbreak of GES-6-producing Serratia marcescens during the COVID-19 pandemic in Spain. METHODS: Retrospective study to describe a GES-CPSM outbreak based on whole genome sequencing and antimicrobial susceptibility testing (AST). Transferability of blaGES-carrying plasmid was assessed by conjugation experiments. RESULTS: In December 2020, we identified a cluster of S. marcescens harbouring blaGES-6 involving 9 patients. Whole-genome sequence analysis revealed a clonal relationship (≤3 SNPs) between the first isolates identified in each of the evolved patients and environmental samples with GES-CPSM detection. Plasmid analysis showed that the blaGES-6 gene was located in an IncQ3-type plasmid. Triparental mating experiments using a helper plasmid demonstrated mobilization of the blaGES-6-carrying plasmid. Our results also demonstrate within-host evolution in S. marcescens isolates, leading to a transition from blaGES-6 to the new blaGES-55, caused by the P162S mutation, in a subsequent infection in one of the affected patients. In blaGES-55 we identified emergence of ceftazidime-avibactam resistance along with an increase of carbapenems susceptibility. This patient had been treated with a 14-day course of ceftazidime-avibactam. AST of the transformants bearing blaGES-6 and blaGES-55 plasmids, confirmed susceptibility variation affecting ceftazidime-avibactam and carbapenems. CONCLUSIONS: We report an unusual outbreak of GES-6 whose incidence is becoming increasing. Transition from GES-6 to GES-55 may readily occur in vivo leading to ceftazidime-avibactam resistance, which brings to the fore the critical need for developing more accurate diagnosis tools for detection of GES ß-lactamases and optimise the use of antimicrobials.

Rapid and Accurate Detection of the SARS-CoV-2 Omicron Variant with a CRISPR-Cas12a Reaction in the RT-qPCR Pot.

Gene sequencing in back of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is the current approach for discriminating infections produced by different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the clinic. However, sequencing is often a time-consuming step, which hinders the deployment of a very fast response during a pandemic. Here, we propose to run a CRISPR-Cas12a reaction after completing the RT-qPCR and in the very same pot to detect with high specificity genetic marks characterizing variants of concern. A crRNA was appropriately designed to detect the S gene of the SARS-CoV-2 Omicron BA.1 variant. A significant response with >20-fold dynamic range was obtained for the Omicron BA.1 S gene, while the Delta S gene did not produce any detectable signal. The sensitivity of the method was analyzed with a series of diluted samples and different Cas12a nucleases. A correlation between the RT-qPCR CT values and the CRISPR-Cas12a reaction signals was observed. Variant discrimination with the CRISPR-Cas12a reaction was possible in some minutes with high accuracy from patient samples. In conclusion, CRISPR-Cas systems seem ready to be exploited in the clinic to boost personalized diagnoses and accelerate epidemiological surveillance in a cost-effective way.

Cognitive telerehabilitation: an expert consensus paper on current evidence and future perspective.

The progressive improvement of the living conditions and medical care of the population in industrialized countries has led to improvement in healthcare interventions, including rehabilitation. From this perspective, Telerehabilitation (TR) plays an important role. TR consists of the application of telemedicine to rehabilitation to offer remote rehabilitation services to the population unable to reach healthcare. TR integrates therapy-recovery-assistance, with continuity of treatments, aimed at neurological and psychological recovery, involving the patient in a family environment, with an active role also of the caregivers. This leads to reduced healthcare costs and improves the continuity of specialist care, as well as showing efficacy for the treatment of cognitive disorders, and leading to advantages for patients and their families, such as avoiding travel, reducing associated costs, improving the frequency, continuity, and comfort of performing the rehabilitation in its own spaces, times and arrangements. The aim of this consensus paper is to investigate the current evidence on the use and effectiveness of TR in the cognitive field, trying to also suggest some recommendations and future perspectives. To the best of our knowledge, this is the first consensus paper among multiple expert researchers that comprehensively examines TR in different neurological diseases. Our results supported the efficacy and feasibility of TR with good adherence and no adverse events among patients. Our consensus summarizes the current evidence for the application of cognitive TR in neurological populations, highlighting the potential of this tool, but also the limitations that need to be explored further.

An immersive virtual reality tool for assessing left and right unilateral spatial neglect.

The reported rate of the occurrence of unilateral spatial neglect (USN) is highly variable likely due to the lack of validity and low sensitivity of classical tools used to assess it. Virtual reality (VR) assessments try to overcome these limitations by proposing immersive and complex environments. Nevertheless, existing VR-based tasks are mostly focused only on near space and lack analysis of psychometric properties and/or clinical validation. The present study evaluates the clinical validity and sensitivity of a new immersive VR-based task to assess USN in the extra-personal space and examines the neuronal correlates of deficits of far space exploration. The task was administrated to two groups of patients with right (N = 28) or left (N = 11) hemispheric brain lesions, also undergoing classical paper-and-pencil assessment, as well as a group of healthy participants. Our VR-based task detected 44% of neglect cases compared to 31% by paper-and-pencil tests in the total sample. Importantly, 30% of the patients (with right or left brain lesions) with no clear sign of USN on the paper-and-pencil tests performed outside the normal range in the VR-based task. Voxel lesion-symptom mapping revealed that deficits detected in VR were associated with lesions in insular and temporal cortex, part of the neural network involved in spatial processing. These results show that our immersive VR-based task is efficient and sensitive in detecting mild to strong manifestations of USN affecting the extra-personal space, which may be undetected using standard tools.

Sex hormones and the total testosterone:estradiol ratio as predictors of severe acute respiratory syndrome coronavirus 2 infection in hospitalized men.

BACKGROUND: The predictive ability of the early determination of sex steroids and the total testosterone:estradiol ratio for the risk of severe coronavirus disease 2019 or the potential existence of a biological gradient in this relationship has not been evaluated. OBJECTIVES: To assess the relationship of sex steroid levels and the total testosterone:estradiol ratio with the risk of severe acute respiratory syndrome coronavirus 2 infection in men, defined as the need for intensive care unit admission or death, and the predictive ability of each biomarker. MATERIALS AND METHODS: This was a prospective observational study. We included all consecutive adult men with severe acute respiratory syndrome coronavirus 2 infections in a single center admitted to a general hospital ward or to the intensive care unit. Sex steroids were evaluated at the centralized laboratory of our hospital. RESULTS: We recruited 98 patients, 54 (55.1%) of whom developed severe coronavirus disease in 2019. Compared to patients with nonsevere coronavirus disease 2019, patients with severe coronavirus disease 2019 had significantly lower serum levels of total testosterone (111 ± 89 vs. 191 ± 143 ng/dL; p < 0.001), dehydroepiandrosterone (1.69 ± 1.26 vs. 2.96 ± 2.64 ng/mL; p < 0.001), and dehydroepiandrosterone sulfate (91.72 ± 76.20 vs. 134.28 ± 98.261 µg/dL; p = 0.009), significantly higher levels of estradiol (64.61 ± 59.35 vs. 33.78 ± 13.78 pg/mL; p = 0.001), and significantly lower total testosterone:estradiol ratio (0.28 ± 0.31 vs. 0.70 ± 0.75; p < 0.001). The lower the serum level of androgen and the lower the total testosterone:estradiol ratio values, the higher the likelihood of developing severe coronavirus disease 2019, with the linear trend in the adjusted analyses being statistically significant for all parameters except for androstenedione (p = 0.064). In the receiver operating characteristic analysis, better predictive performance was shown by the total testosterone:estradiol ratio, with an area under the curve of 0.77 (95% confidence interval 0.68-0.87; p < 0.001). DISCUSSION AND CONCLUSION: Our results suggest that men with severe acute respiratory syndrome coronavirus 2 infection, decreased androgen levels and increased estradiol levels have a higher likelihood of developing an unfavorable outcome. The total testosterone:estradiol ratio showed the best predictive ability.

Pertinencia de la superación posgraduada en correspondencia con los problemas de salud en Villa Clara / Relevance of postgraduate improvement in correspondence with health problems in Villa Clara

Fundamento: en la Universidad de Ciencias Médicas de Villa Clara se ha diseñado e implementado una estrategia metodológica para lograr mayor relación de la superación profesional con el cuadro de salud. Objetivo: exponer los resultados de la superación profesional en correspondencia con los principales problemas de salud en Villa Clara. Métodos: se realizó un estudio descriptivo con diseño transversal de la superación profesional vinculada al posgrado en el periodo 2017-2021. Se aplicaron métodos teóricos, empíricos y matemático-estadísticos; la información obtenida se presentó en tablas con valores absolutos y relativos. Resultados: del total de actividades planificadas, el 83,01 % respondieron a los problemas de salud de la provincia. Relacionado con las enfermedades crónicas no transmisibles se efectuaron 542; tumores malignos, 179; Programa de Atención Materno Infantil, 1762; y Programa de Atención al Adulto Mayor, 198. Sobre otras enfermedades transmisibles, su mayor número estuvo en el 2019. En el 2020 predominaron las vinculadas a las arbovirosis y la pandemia de la COVID-19 cuando se capacitaron un total de 325 880 profesionales en el 2020 y 5839 en el 2021. Conclusiones: la superación posgraduada de los profesionales de la salud en Villa Clara se ha correspondido con los principales problemas de la salud del territorio en los años del 2017 al 2021 lo cual evidencia pertinencia y progreso en la continuidad de la formación académica del capital humano.

Background: at Villa Clara University of Medical Sciences, a methodological strategy has been designed and implemented to achieve a greater relationship between professional improvement and health status. Objective: to present the results of professional improvement in correspondence with the main health problems in Villa Clara. Methods: a descriptive study was carried out with a cross-sectional design of professional improvement linked to postgraduate studies from 2017 to 2021. Theoretical, empirical and mathematical-statistical methods were applied; the information obtained was presented in tables with absolute and relative values. Results: out of the whole activities, 83.01% responded to the health problems of the province. Related to chronic non-transmissible diseases, 542 were carried out; malignant tumors, 179; Maternal and Child Care Program, 1762; and the Elderly Care Program, 198. Regarding other transmissible diseases, the highest number was in 2019. In 2020, those linked to arboviruses and the COVID-19 pandemic predominated when a total of 325,880 professionals were trained in 2020 and 5839 in 2021. Conclusions: the postgraduate improvement of health professionals in Villa Clara has corresponded to the main health problems of the territory in the years from 2017 to 2021, which shows relevance and progress in the continuity of the academic training of human capital.

Intracranial leptomeningeal CNS ganglioneuroblastoma. First report and review of the literature.

BACKGROUND: CNS ganglioneuroblastoma in an extremely rare embryonal tumour, specifically in the pediatric population. Bad prognosis is documented due to aggressiveness and absence of protocolized treatment at the moment. CLINICAL DESCRIPTION: We present the case of a 5-year-old boy who presented with sudden loss of consciousness. CT scan was performed showing a large posterior fossa lesion with several intraventricular focal lesions, suggesting metastases, the largest one located inside the III ventricle. The patient underwent a posterior fossa resection of the lesion and a subtotal resection of the III ventricle lesion, with adjuvant chemotherapy. The evolution was poor and the patient finally died 3 months after diagnosis. CONCLUSION: Ganglioneuroblastoma is extremely likely to recur quickly and extensively. There is little knowledge about treatment options but is documented that gross total resection followed by adjuvant radiotherapy and chemotherapy is the best management in these patients.

Palbociclib releases the latent differentiation capacity of neuroblastoma cells.

Neuroblastoma is the most common extracranial solid tumor in infants, arising from developmentally stalled neural crest-derived cells. Driving tumor differentiation is a promising therapeutic approach for this devastating disease. Here, we show that the CDK4/6 inhibitor palbociclib not only inhibits proliferation but induces extensive neuronal differentiation of adrenergic neuroblastoma cells. Palbociclib-mediated differentiation is manifested by extensive phenotypic and transcriptional changes accompanied by the establishment of an epigenetic program driving expression of mature neuronal features. In vivo palbociclib significantly inhibits tumor growth in mouse neuroblastoma models. Furthermore, dual treatment with retinoic acid resets the oncogenic adrenergic core regulatory circuit of neuroblastoma cells, further suppresses proliferation, and can enhance differentiation, altering gene expression in ways that significantly correlate with improved patient survival. We therefore identify palbociclib as a therapeutic approach to dramatically enhance neuroblastoma differentiation efficacy that could be used in combination with retinoic acid to improve patient outcomes.

CRISPR-Cas13a-Based Assay for Accurate Detection of OXA-48 and GES Carbapenemases.

Carbapenem-resistant pathogens have been recognized as a health concern as they are both difficult to treat and detect in clinical microbiology laboratories. Researchers are making great efforts to develop highly specific, sensitive, accurate, and rapid diagnostic techniques, required to prevent the spread of these microorganisms and improve the prognosis of patients. In this context, CRISPR-Cas systems are proposed as promising tools for the development of diagnostic methods due to their high specificity; the Cas13a endonuclease can discriminate single nucleotide changes and displays collateral cleavage activity against single-stranded RNA molecules when activated. This technology is usually combined with isothermal pre-amplification reactions in order to increase its sensitivity. We have developed a new LAMP-CRISPR-Cas13a-based assay for the detection of OXA-48 and GES carbapenemases in clinical samples without the need for nucleic acid purification and concentration. To evaluate the assay, we used 68 OXA-48-like-producing Klebsiella pneumoniae clinical isolates as well as 64 Enterobacter cloacae complex GES-6, 14 Pseudomonas aeruginosa GES-5, 9 Serratia marcescens GES-6, 5 P. aeruginosa GES-6, and 3 P. aeruginosa (GES-15, GES-27, and GES-40) and 1 K. pneumoniae GES-2 isolates. The assay, which takes less than 2 h and costs approximately 10 € per reaction, exhibited 100% specificity and sensitivity (99% confidence interval [CI]) for both OXA-48 and all GES carbapenemases. IMPORTANCE Carbapenems are one of the last-resort antibiotics for defense against multidrug-resistant pathogens. Multiple nucleic acid amplification methods, including multiplex PCR, multiplex loop-mediated isothermal amplification (LAMP) and multiplex RPAs, can achieve rapid, accurate, and simultaneous detection of several resistance genes to carbapenems in a single reaction. However, these assays need thermal cycling steps and specialized instruments, giving them limited application in the field. In this work, we adapted with high specificity and sensitivity values, a new LAMP CRISPR-Cas13a-based assay for the detection of OXA-48 and GES carbapenemases in clinical samples without the need for RNA extraction.

Intermittent Fasting Promotes Weight Loss without Decreasing Performance in Taekwondo.

Intermittent fasting (IF) is commonly used by combat sports athletes for weight loss. However, IF can decrease performance. This study aimed to investigate the effect of IF on total body mass (TBM) and Taekwondo performance. Nine athletes (seven male, two female; 18.4 ± 3.3 years) underwent 4 weeks of 12 h IF. TBM, countermovement jump (CMJ), mean kicks (MK), and total number of kicks (TNK) were compared weekly. Performance was measured in the fed state (FED) and fast state (FAST). Results showed decreased TBM in week 1 (62.20 ± 6.56 kg; p = 0.001) and week 2 (62.38 ± 6.83 kg; p = 0.022) compared to pre-intervention (63.58 ± 6.57 kg), stabilizing in week 3 (62.42 ± 6.12 kg), and no significant change in week 4 (63.36 ± 6.20 kg). CMJ performance in week 1 was lower in FED (35.26 ± 7.15 cm) than FAST (37.36 ± 6.77 cm; p = 0.003), but in week 3, FED (38.24 ± 6.45 cm) was higher than FAST (35.96 ± 5.05 cm; p = 0.047). No significant differences were found in MK and TNK in FSKTmult. RPE, KDI, and HR were similar between FED and FAST (p < 0.05). [LAC] was higher post-test compared to pre-test (p = 0.001), with higher concentrations in FED than FAST (p = 0.020). BG was higher in FED than FAST (p < 0.05) before physical tests. Therefore, IF promotes decreased TBM without decreasing performance.

Identificação de um paciente com hanseníase multibacilar por meio do teste sorológico (LID) em ações de busca ativa: um relato de caso / Identification of a patient with multibacillary leprosy using the serological test (LID) in active search actions: a case report

A hanseníase é uma doença crônica e infectocontagiosa causada pelo Mycobacterium leprae (M. leprae). Apresenta alta infectividade e baixa patogenicidade. O estudo teve como objetivo relatar a identificação de um paciente com hanseníase multibacilar através do teste sorológico (LID) em ação de busca ativa. Paciente do sexo masculino, 54 anos, residente em Governador Valadares, Minas Gerais, Brasil, proveniente da busca ativa do Núcleo de Pesquisa em Hansenologia (NuPqHans/UFJF-GV), apresentou teste sorológico positivo para proteínas recombinantes do bacilo (ML0405/ML2331). Encaminhado ao Centro de Referência de Doenças Endêmicas e Programas Especiais (CREDENPES), queixando-se de lesões na pele e nódulos pelo corpo, relatou histórico de traumas na cabeça, tonturas ocasionais, dormência nos pés e sangramento nasal. O paciente apresentou resultados de baciloscopia e biopsia positivos, concluindo o diagnóstico de hanseníase multibacilar, recebendo poliquimioterapia indicada. Após três meses de tratamento observou-se redução na área/diâmetro das lesões do abdômen, indicando a eficácia do tratamento. O resultado positivo do teste sorológico, permitiu a identificação de um paciente multibacilar, até então sem diagnóstico de hanseníase. Ademais, a utilização do teste sorológico LID nas atividades de busca ativa em áreas endêmicas para realização do diagnóstico precoce pode contribuir para o conceito zero hanseníase estipulado pela Organização Mundial da Saúde. (AU).

Leprosy is a chronic and infectious disease caused by Mycobacterium leprae (M. leprae). It has high infectivity and low pathogenicity. The aim of this study was to report the identification of a patient with multibacillary leprosy using the serological test (LID) during an active search. A 54-year-old male patient, living in Governador Valadares, Minas Gerais, Brazil, from the active search of the Leprosy Research Center (NuPqHans/UFJF-GV), presented a positive serological test for recombinant bacillus proteins (ML0405/ML2331). He was referred to the Reference Center for Endemic Diseases and Special Programs (CREDENPES), complaining of skin lesions and nodules all over his body, and reported a history of head trauma, occasional dizziness, numbness in his feet, and nosebleeds. The patient presented positive bacilloscopy and biopsy results, concluding the diagnosis of multibacillary leprosy and receiving the indicated multidrug therapy. After three months of treatment, there was a reduction in the area/diameter of the lesions on the abdomen, indicating the effectiveness of the treatment. The positive result of the serological test (LID) allowed the identification of a multibacillary patient, who until then had not been diagnosed with leprosy. In addition, the use of the LID serological test in active search activities in endemic areas for early diagnosis can contribute to the zero-leprosy concept stipulated by the World Health Organization. (AU)

Outbreak of Arcobacter butzleri? An emerging enteropathogen.

BACKGROUND: Arcobacter butzleri is a gram-negative rod, with microaerobic growth at an optimal temperature of 37°C. It was reported to be the fourth most common Campylobacter-like organism isolated from patients with diarrhoea. OBJECTIVE: Characterise a potential outbreak of A. butzleri detected in a short period of time in the University Hospital Marqués de Valdecilla. METHODS: Eight strains of A. butzleri were detected in our hospital in only two months. Isolates were identified by MALDI-TOF MS system and 16S rDNA sequencing. Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) and Pulsed Field Gel Electrophoresis (PFGE) were carried out to assess clonal relationship. Gradient strips (Etest) were used to determine susceptibility by agar diffusion. RESULTS: ERIC-PCR and PFGE confirmed the lack of clonal relationship between strains. Erythromycin or ciprofloxacin might be appropriate for antibiotic treatment of infections. CONCLUSIONS: A. butzleri is an emerging pathogen with increasing incidence, and may be underestimated.

An immersive virtual reality system for ecological assessment of peripersonal and extrapersonal unilateral spatial neglect.

BACKGROUND: Unilateral spatial neglect (USN) is a debilitating neuropsychological syndrome that often follows brain injury, in particular a stroke affecting the right hemisphere. In current clinical practice, the assessment of neglect is based on old-fashioned paper-and-pencil and behavioral tasks, and sometimes relies on the examiner's subjective judgment. Therefore, there is a need for more exhaustive, objective and ecological assessments of USN. METHODS: In this paper, we present two tasks in immersive virtual reality to assess peripersonal and extrapersonal USN. The tasks are designed with several levels of difficulty to increase sensitivity of the assessment. We then validate the feasibility of both assessments in a group of healthy adult participants. RESULTS: We report data from a study with a group of neurologically unimpaired participants (N = 39). The results yield positive feedback on comfort, usability and design of the tasks. We propose new objective scores based on participant's performance captured by head gaze and hand position information, including, for instance, time of exploration, moving time towards left/right and time-to-reach, which could be used for the evaluation of the attentional spatial bias with neurological patients. Together with the number of omissions, the new proposed parameters can result in lateralized index ratios as a measure of asymmetry in space exploration. CONCLUSIONS: We presented two innovative assessments for USN based on immersive virtual reality, evaluating the far and the near space, using ecological tasks in multimodal, realistic environments. The proposed protocols and objective scores can help distinguish neurological patients with and without USN.

Evaluación de resultados en una serie de pacientes con trasplante cardiaco: experiencia en el Instituto Nacional de Cardiología

Exponemos la experiencia del Instituto Nacional de Cardiología de una serie de casos de pacientes sometidos a trasplante cardiaco entre mayo de 2016 y junio 2022. Se realizaron 14 trasplantes, 13 fueron del sexo masculino. La edad osciló entre 19 y 62 años. Las etiologías fueron cardiopatías de tipo idiopática en 57% y valvular en 21%. El 50% se trasplantó en INTERMACS 4 (Interagency Registry for Mechanically Assisted Circulatory Support), 21% INTERMACS 3 y solo 28% en INTERMACS 2. Tres pacientes se trasplantaron con asistencia circulatoria tipo membrana circulación extracorpórea. Las complicaciones más frecuentes fueron las infecciosas. La mortalidad hospitalaria fue 35,7%. Hubo un fallecido en el seguimiento tras 5 años de trasplante.

We present the experience of the National Institute of Cardiology of a series of cases of patients undergoing heart transplantation between May 2016 and June 2022. Fourteen transplants were performed, 13 of the patients were male. The age ranged between 19 and 62 years. The etiologies were idiopathic heart disease in 57% and valvular heart disease in 21%. Fifty percent was transplanted in INTERMACS 4 (Interagency Registry for Mechanically Assisted Circulatory Support), 21% in INTERMACS 3 and only 28% in INTERMACS 2. Three patients were transplanted with membrane type extracorporeal circulation circulatory support. The most frequent complications were infectious. Hospital mortality was 35.7%. There was one patient who died during follow-up after 5 years of transplantation.

Establishing a molecular laboratory in COVID-19 pandemic: The experience of a regional laboratory in Spain.

The high demand for COVID-19 diagnosis overwhelmed reference hospitals. Regional laboratories had to incorporate molecular technology to respond to the emergency. This work described the implementation of molecular diagnostic tools and the detection of SARS-CoV-2, in a regional hospital with no previous experience, from October 2020 to March 2022. The laboratory structure was significantly modified. The staff grew from 3 to 4 clinical microbiologists, and from 7 to 17 laboratory technicians to provide 24/7 coverage. A total of 144,442 samples were processed during the period of study. The highest peaks were reached in July 2021 with 25,285 samples processed, and between December 2021 and January 2022, with 32,245. COVID-19 pandemic has represented not only the challenge, but the opportunity to introduce Nucleic Acid Amplification Techniques (NAAT) in inexperienced laboratories. These secondary settings have shown an extraordinary ability to adapt and cannot be left behind in the progress of diagnostic techniques.

Safety of upadacitinib in Latin American patients with rheumatoid arthritis: an integrated safety analysis of the SELECT phase 3 clinical program.

INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by ongoing inflammation and degradation of synovial joints. The oral JAK inhibitor, upadacitinib, is approved for RA. We conducted an integrated safety analysis of upadacitinib 15 mg once daily (QD) in patients from Latin America (LATAM) versus the rest of the world (RoW). METHODS: Treatment-emergent adverse events (AEs) and laboratory data from six phase 3, randomized controlled trials, adjusted for upadacitinib 15 mg QD use in RA, were analyzed. RESULTS: Overall, 3209 patients received upadacitinib 15 mg QD for 7024 patient-years (PY). LATAM patients (n = 725) had a mean upadacitinib exposure of 1518 PY. Baseline characteristics were generally similar between LATAM and RoW populations. AE rates (including serious/opportunistic infections, tuberculosis, and herpes zoster) and deaths were comparable between populations. LATAM patients had lower serious AE rates per 100 PY (9.4 vs 14.0 E/100 PY) and discontinuation-related AEs (3.9 vs 6.0 E/100 PY) versus RoW. Rates of cardiovascular events were low (≤ 0.5 E/100 PY) and similar between populations. Malignancies, excluding non-melanoma skin cancer, were less common in the LATAM population versus RoW (0.2 vs 1.0 E/100 PY). Laboratory abnormalities were similar between populations, with decreases in hemoglobin, lymphocyte, and neutrophil counts, and elevations in liver enzymes and creatine phosphokinase. Mean change from baseline in low- and high-density lipoprotein cholesterol was generally comparable between LATAM and RoW populations. CONCLUSION: Upadacitinib 15 mg QD demonstrated a consistent safety profile across LATAM and RoW patient populations, with no new safety risks observed. TRIAL REGISTRATION NUMBERS: SELECT-EARLY, NCT02706873; SELECT-NEXT, NCT02675426; SELECT-COMPARE, NCT02629159; SELECT-MONOTHERAPY, NCT02706951; SELECT-BEYOND, NCT02706847; SELECT-CHOICE, NCT03086343.

In vitro activity of ceftobiprole and dalbavancin against a collection of coagulase-negative staphylococci isolates from clinical samples with reduced susceptibility to daptomycin and/or resistant to linezolid or glycopeptides.

INTRODUCTION: The aim was to investigate the in vitro activity of ceftobiprole and dalbavancin against a collection of coagulase-negative staphylococci (CoNS) isolates with reduced susceptibility to daptomycin or resistant to linezolid and/or glycopeptides. METHODS: A total of 228 CoNS were tested using the Vitek-2 AST-626 cards (bioMérieux) and MIC of daptomycin, linezolid, vancomycin and teicoplanin were confirmed by Etest Strips (bioMérieux). Susceptibility testing for ceftobiprole and dalbavancin were performed by CLSI broth microdilution methodology. Results were interpreted according to 2021 EUCAST clinical breakpoints. RESULTS: Ceftobiprole and dalbavancin were active against 96.0% and 93.0% of CoNS, respectively, MIC90 were 2 and 0.125mg/L. MICs of ceptobiprole were higher against S. hominis and S. haemolyticus (MIC90 4mg/L). Dalbavancin exhibited higher MICs against S. haemolyticus and CoNS with reduced susceptibility to daptomycin and resistant to teicoplanin. CONCLUSION: Ceftobiprole and dalbavancin demonstrated a high in vitro activity against our collection of CoNS isolates.

Double ventriculo-gallbladder shunt in the treatment of giant suprasellar arachnoid cyst with secondary hydrocephalus.

Ventriculo-gallbladder shunt is described as an effective alternative procedure in the treatment of hydrocephalus. We present the case of a 19-year-old patient diagnosed with suprasellar arachnoid cyst since his childhood and hydrocephalus, with a double shunt; ventriculo peritoneal and peritoneal cyst shunt. After several replacements due to peritoneal failure, he underwent ventriculoatrial shunt, with associated complications and subsequent repositioning to the peritoneum. After new valve dysfunction due to peritoneal complications, ventriculo-gallbladder shunt was proposed as an alternative treatment for this patient, which was safe and effective in resolving the patient's symptoms, and the patient was discharged, maintaining clinical stability in the follow-up more than 2 years later.

From the laboratory to the field: efficacy of entomopathogenic nematodes to control the cattle tick.

BACKGROUND: The control of ticks is challenged by the resistance of tick populations to chemical acaricides. In this study, we evaluated, under laboratory conditions, the efficacy of Heterorhabditis bacteriophora against Rhipicephalus (Boophilus) microplus engorged females with varying body weights (150, 200, 250, 300 or 350 mg per female) or from eight different geographical populations. We also determined the efficacy of H. bacteriophora for tick control under field conditions. RESULTS: R. microplus engorged females with varying body weights exposed to 150 juveniles of H. bacteriophora resulted in a high control efficacy (97.5% to 98.4%). Tests with females from different geographical populations comprised eight tick strains treated with H. bacteriophora and their respective control groups. The biological parameters of females exposed to nematode treatments did not differ significantly and resulted in 89% to 99% of control efficacy. Trials conducted under field conditions were performed in field plots with Megathyrsus maximus grass. Treatment groups received eight cadavers of Tenebrio molitor fully colonized with H. bacteriophora at 1 week prior to the release of female ticks, whereas control groups were untreated. On the first day of the experiment, six engorged females were distributed in each plot. On day 42 and day 63, the apical portion of the grasses with R. microplus larvae were collected and quantified. The population of R. microplus larvae was reduced up to 73.1% in plots treated with H. bacteriophora at day 63 after treatment. CONCLUSION: R. microplus engorged females with varying body weights or from different geographical populations were highly susceptible to H. bacteriophora. The field test demonstrated the efficacy of H. bacteriophora in reducing R. microplus larvae in infested pastures. © 2022 Society of Chemical Industry.