Simultaneous detection of pathogens and antimicrobial resistance genes with the open source, cloud-based, CZ ID pipeline.

Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the CZ ID AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data. It leverages the Comprehensive Antibiotic Resistance Database and associated Resistance Gene Identifier software, and works synergistically with the CZ ID short-read mNGS module to enable broad detection of both microbes and AMR genes. We highlight diverse applications of the AMR module through analysis of both publicly available and newly generated mNGS and WGS data from four clinical cohort studies and an environmental surveillance project. Through genomic investigations of bacterial sepsis and pneumonia cases, hospital outbreaks, and wastewater surveillance data, we gain a deeper understanding of infectious agents and their resistomes, highlighting the value of integrating microbial identification and AMR profiling for both research and public health. We leverage additional functionalities of the CZ ID mNGS platform to couple resistome profiling with the assessment of phylogenetic relationships between nosocomial pathogens, and further demonstrate the potential to capture the longitudinal dynamics of pathogen and AMR genes in hospital acquired bacterial infections. In sum, the new AMR module advances the capabilities of the open-access CZ ID microbial bioinformatics platform by integrating pathogen detection and AMR profiling from mNGS and WGS data. Its development represents a critical step toward democratizing pathogen genomic analysis and supporting collaborative efforts to combat the growing threat of AMR.

Simultaneous detection of pathogens and antimicrobial resistance genes with the open source, cloud-based, CZ ID pipeline.

Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the Chan Zuckerberg ID (CZ ID) AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data. It leverages the Comprehensive Antibiotic Resistance Database and associated Resistance Gene Identifier software, and works synergistically with the CZ ID short-read mNGS module to enable broad detection of both microbes and AMR genes. We highlight diverse applications of the AMR module through analysis of both publicly available and newly generated mNGS and WGS data from four clinical cohort studies and an environmental surveillance project. Through genomic investigations of bacterial sepsis and pneumonia cases, hospital outbreaks, and wastewater surveillance data, we gain a deeper understanding of infectious agents and their resistomes, highlighting the value of integrating microbial identification and AMR profiling for both research and public health. We leverage additional functionalities of the CZ ID mNGS platform to couple resistome profiling with the assessment of phylogenetic relationships between nosocomial pathogens, and further demonstrate the potential to capture the longitudinal dynamics of pathogen and AMR genes in hospital acquired bacterial infections. In sum, the new AMR module advances the capabilities of the open-access CZ ID microbial bioinformatics platform by integrating pathogen detection and AMR profiling from mNGS and WGS data. Its development represents a critical step toward democratizing pathogen genomic analysis and supporting collaborative efforts to combat the growing threat of AMR.

Non-Infectious Uveitis and Pregnancy, is There an Optimal Treatment? Uveitis Course and Safety of Uveitis Treatment in Pregnancy.

In pregnancy, a plethora of factors causes changes in maternal immunity. Uveitis flare-ups are more frequent in the first trimester and in undertreated patients. Management of non-infectious uveitis during pregnancy remains understudied. A bibliographic review to consolidate existing evidence was performed by a multidisciplinary group of Ophthalmologists, Gynaecologists and Rheumatologists. Our group recommends initial management with minimum-required doses of corticosteroids, preferably locally, to treat intraocular inflammation whilst ensuring good neonatal outcomes. If ineffective, clinicians should consider addition of Cyclosporine, Azathioprine or Certolizumab pegol, which are seemingly safe in pregnancy. Other therapies (such as Methotrexate, Mycophenolate Mofetil and alkylating agents) are teratogenic or have a detrimental effect on the foetus. Furthermore, careful multidisciplinary preconception discussions and close follow-up are recommended, monitoring for flare-ups and actively tapering medication doses, with a primary endpoint focused on protecting ocular tissues from inflammation, whilst giving minimal risk of poor pregnancy and foetal outcomes.

Infección oral y cervicofacial por agranulocitosis secundario debido al tratamiento con medicación antitiroidea: Reporte de Caso / Oral and Cervicofacial Infection Secondary to Agranulocytosis Caused by Antithyroid Medication: A Case Report

RESUMEN La agranulocitosis es el recuento bajo de glóbulos blancos (neutrófilos), que puede ser inducida por tratamientos con algunos medicamentos como los antitiroideos, que ocasionan manifestaciones orales como úlceras o necrosis gingival difusa. Se presenta el caso de una paciente mujer de 26 años, con antecedente de hipertiroidismo, quien acude a emergencia del Hospital Nacional Alberto Sabogal Sologuren por presentar tumefacción en la hemicara izquierda, asociada a disfagia, múltiples lesiones ulceradas en mucosa oral, con compromiso de tejido óseo, fiebre y malestar general. Luego de los exámenes auxiliares, se categoriza como una infección oral y cervicofacial por agranulocitosis debido al tratamiento con el metimazol. La literatura mundial reporta casos de agranulocitosis como efecto adverso del consumo de drogas antitiroideas, con reporte de manifestaciones orales; sin embargo, pocos casos evidencian compromiso cervical. Por lo cual se presenta este caso poco usual desde su diagnóstico hasta el tratamiento.

ABSTRACT Agranulocytosis refers to a low white blood cell count, specifically neutrophils, which can be caused by certain medications such as antithyroid drugs (ATD). This condition can result in oral manifestations, including diffuse gingival ulceration or necrosis. We present the case of a 26-year-old female patient with a history of hyperthyroidism who came to the emergency department of Alberto Sabogal Sologuren National Hospital with swelling on the left side of her face, accompanied by dysphagia, multiple ulcerated lesions in the oral mucosa involving bone tissue, as well as fever and general malaise. After conducting additional tests, the patient was diagnosed with oral and cervicofacial infection secondary to agranulocytosis caused by methimazole treatment. While the global literature reports cases of agranulocytosis as an adverse effect of antithyroid medication, with documented oral manifestations, only a few cases demonstrate cervical involvement. Therefore, we present this uncommon case from diagnosis to treatment.

First Report of Tocilizumab Use in a Cohort of Latin American Patients Hospitalized for Severe COVID-19 Pneumonia.

Introduction/objectives: An interleukin-6 inhibition strategy could be effective in selected COVID-19 patients. The objective is to present our experience of tocilizumab use in patients with severe COVID-19. Methods: Observational retrospective cohort study. Hospitalized patients were evaluated by our multidisciplinary team for eventual use of tocilizumab. Patients with progressive ventilatory impairment and evidence of a hyperinflammatory state despite usual treatment received tocilizumab 8 mg/kg intravenous (maximum dose 800 mg), in addition to standard treatment. The use and time of use of mechanical ventilation (MV), the change of the Alveolar-arterial (A-a) gradient, of the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) and of inflammation laboratory parameters after 72 h of tocilizumab use was evaluated. Results: 29 patients received tocilizumab. 93.1% were men, 37.9% were obese, and 34.5% had hypertension. Of the 20 patients who were not on MV when receiving tocilizumab, 11 required non-invasive MV, for an average of 5 days, and one of them required intubation. A-a gradient, PaO2/FiO2, and inflammation parameters improved significantly. A better lymphocyte count, which improved significantly after tocilizumab use, was significantly associated with less use of MV. Five patients presented positive culture samples after tocilizumab, three being of clinical significance. A lower lymphocyte count was associated with having a positive culture. No other significant adverse events were seen. Conclusion: Our study suggests the utility and shows the safety of tocilizumab use in COVID-19 patients who have respiratory failure and evidence of hyperinflammation. Lymphocyte improvement was a predictor of good response.

Hydroxychloroquine and chloroquine in COVID-19: should they be used as standard therapy?

The pandemic of the new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has urged the nations to an unprecedented world-wide reaction, including an accelerated exploration of therapeutic options. In the absence of a vaccine and specifically designed antivirals, the medical community has proposed the use of various previously available medications in order to reduce the number of patients requiring prolonged hospitalizations, oxygen therapy, and mechanical ventilation and to decrease mortality from coronavirus disease 2019 (COVID-19). Hydroxychloroquine and chloroquine are among the proposed drugs and are the most widely used so far, despite the lack of robust evidence on their usefulness. The objective of this article is to review and discuss the possible role of these drugs in the therapy of COVID-19.

Artritis psoriásica: La elección del fármaco antirreumático biológico en la Ley Ricarte Soto / Choosing biological agents for the treatment of psoriatic arthritis

The financial coverage granted by law in Chile for patients with psoriatic arthritis who require biological treatment is of paramount importance and a great advance. However physicians must be knowledgeable about the advantages and limitations of this therapy. The challenge of clinicians is to choose the drug with the greater odds of achieving therapeutic success, with less adverse events and lower costs for our health system. This article aims to help doctors to select the best biological treatment for a specific patient, trying to optimize its effectiveness, minimizing adverse effects, always looking for an efficient use of resources.

Patients with axial spondyloarthritis report significant differences between men and women and high impact of the disease: Large websurvey analysis.

OBJECTIVE: In axial spondyloarthritis (axSpA), mounting evidence shows female patients to experience a higher disease burden. These differences appear to be particularly large in South America. One explanation could be inequity in treatment access between men and women. The objective was to evaluate gender differences in disease burden and work participation, and the potential influence of treatment, in Latin American patients. METHODS: A cross sectional online survey among axSpA patients, collecting disease characteristics, treatment, disease burden (BASDAI, BASFI, ASAS Health Index) and work participation (WPAI). Associations between gender and disease burden or work participation were assessed through regression analyses, correcting for treatment. RESULTS: AxSpA was reported by 472 participants (63% women) and disease activity (BASDAI≥4: 83%), ASASHI (≥moderately impaired: 91%) and work disability (absenteeism: 41%; presenteeism 82%) were high. Biological use was very low (20%), while 34% used opiates. Females had significantly higher BASDAI, ASAS HI, work absenteeism and presenteeism, although were less likely to receive biologics (26% versus 16%, P<0.01). Gender differences disappeared after correction for treatment. CONCLUSIONS: This web survey in Latin American axSpA patients shows a high disease burden and work impairment. The use of biologics is low, while the use of opiates was alarmingly high. Women used significantly less biologics despite reporting a worse disease state and work disability, which could be due to treatment inequity.

[Choosing biological agents for the treatment of psoriatic arthritis]. / Artritis psoriásica: La elección del fármaco antirreumático biológico en la Ley Ricarte Soto.

The financial coverage granted by law in Chile for patients with psoriatic arthritis who require biological treatment is of paramount importance and a great advance. However physicians must be knowledgeable about the advantages and limitations of this therapy. The challenge of clinicians is to choose the drug with the greater odds of achieving therapeutic success, with less adverse events and lower costs for our health system. This article aims to help doctors to select the best biological treatment for a specific patient, trying to optimize its effectiveness, minimizing adverse effects, always looking for an efficient use of resources.