Two Decades of Thyroid Nodule Cytology in Children: Malignancy Risk Assessment at a Tertiary Care Center.

INTRODUCTION: Pediatric thyroid nodules exhibit higher malignancy rates compared to adults and are associated with increased incidences of metastases and recurrences. The American Thyroid Association recommends surgery for indeterminate thyroid biopsies in children based on these higher malignancy risks, though this approach may lead to overtreatment. However, there remains a lack of comprehensive pediatric data to inform clinical decisions. This study examines the risk of malignancy (ROM) in pediatric thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and assesses the diagnostic accuracy of fine-needle aspiration biopsy (FNA) compared to histological outcomes. METHODS: A retrospective cross-sectional analysis was performed on patients under 19 years with thyroid nodules who underwent FNA and thyroidectomy at a tertiary care center. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and ROM of cytological biopsies were evaluated using TBSRTC criteria, with histology serving as the gold standard. Two analyses were conducted to assess diagnostic accuracy: (a) TBSRTC II as negative and TBSRTC VI as positive, and (b) TBSRTC II as negative with TBSRTC V and VI as positive. For neoplasia detection, TBSRTC II was deemed negative, while TBSRTC IV, V, and VI were considered positive. TBSRTC categories III and I were excluded from the performance analysis and evaluated separately. Follicular neoplasm or lesions suspicious for follicular neoplasm (FN/SFN) were treated as positive outcomes, correlated with the presence of adenoma or carcinoma in the surgical specimen. RESULTS: Of 75 nodules from 73 patients, 28 (37.3%) were benign and 47 (62.6%) malignant. No significant differences in gender or age were noted between groups. The ROM in each TBSRTC were Bethesda I 0/2, 0%; II 0/13, 0%; III 2/7, 29%: IV 6/14, 43%; V 10/10, 100%, and VI 29/29, 100%, respectively. A sensitivity of 78.38% and specificity of 100% for FNA in detecting malignancy was found, with an even higher sensitivity (100%) for detecting neoplasia in TBSRTC IV. CONCLUSIONS: This study reveals that indeterminate thyroid nodules in pediatric patients exhibit a higher rate of malignancy compared to adults, yet align with rates previously reported in the pediatric population. These findings highlight the critical need for guidelines tailored specifically to the management of thyroid nodules and thyroid cancer in children.

Investigating the 2023 MOGAD Criteria in Children and Adults With MOG-Antibody Positivity Within and Outside Attacks.

BACKGROUND AND OBJECTIVES: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children. METHODS: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing. The primary outcome was to assess the accuracy of the 2023 MOGAD criteria, using as gold standard the most plausible diagnosis after a follow-up >1 year. MOGAD criteria were retrospectively applied assessing core syndromes, supportive clinical-radiological features, and MOG-IgG titers. Patients tested ≤3 months of a disease attack (acute phase) or afterward (remission) were considered separately. The positive predictive value (PPV) of the criteria (true-positive [patients classified as MOGAD and MOGAD diagnosis last follow-up] divided by total positive [all patients classified as MOGAD]), and its 95% CI, was calculated with the Wilson procedure. RESULTS: A total of 257 patients (133 children) were included in the study (median age 15 years [interquartile range 6-38], 54% female). Among 202 patients assessed during a disease attack, 158 (78%) had high MOG-IgG serum titers, 36 (18%) low titers, and 8 (4%) antibodies only in CSF. No differences were identified between patients with high and low titers, but those with low titers were more likely to have an alternative diagnosis at last follow-up (2/36 [6%] vs 0/158, p = 0.012). Supportive features were present in 230 of 257 (89%) patients, regardless of age, MOG-IgG titers, and core syndromes except for optic neuritis in adults whose assessment with orbital MRI was not systematic. Overall, 240 of 257 (94%) patients were well classified by the MOGAD criteria (e.g., 236 eventually having MOGAD and 4 alternative diagnoses), and 17 were wrongly classified (e.g., 11 eventually having MOGAD and 6 alternative diagnoses). Although the criteria classified better during disease attacks than during remissions (187 [96%] vs 49 [89%] serum MOG-IgG-positive patients were well-classified, p = 0.038), the PPV was high in both settings (99% [95% CI 97-100] vs 98% [95% CI 89-100]). DISCUSSION: The 2023 MOGAD criteria correctly identified most children and adults with MOGAD. The highest accuracy occurred when they were applied during disease attacks. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the 2023 MOGAD criteria accurately identify adults and children with MOGAD.

Exploring Synthesis Strategies and Interactions between MOFs and Drugs for Controlled Drug Loading and Release, Characterizing Interactions Through Advanced Techniques.

This study explores various aspects of Metal-Organic Frameworks (MOFs), focusing on synthesis techniques to adjust pore size and key ligands and metals for crafting carrier MOFs. It investigates MOF-drug interactions, including hydrogen bonding, van der Waals, and electrostatic interactions, along with kinetic studies. The multifaceted applications of MOFs in drug delivery systems are elucidated. The morphology and structure of MOFs are intricately linked to synthesis methodology, impacting attributes like crystallinity, porosity, and surface area. Hydrothermal synthesis yields MOFs with high crystallinity, suitable for catalytic applications, while solvothermal synthesis generates MOFs with increased porosity, ideal for gas and liquid adsorption. Understanding MOF-drug interactions is crucial for optimizing drug delivery, affecting charge capacity, stability, and therapeutic efficacy. Kinetic studies determine drug release rates and uniformity, vital for controlled drug delivery. Overall, comprehending drug-MOF interactions and kinetics is essential for developing effective and controllable drug delivery systems.

Smouldering-Associated Worsening in Multiple Sclerosis: An International Consensus Statement on Definition, Biology, Clinical Implications, and Future Directions.

Despite therapeutic suppression of relapses, multiple sclerosis (MS) patients often experience subtle deterioration, which extends beyond the definition of "progression independent of relapsing activity." We propose the concept of smouldering-associated-worsening (SAW), encompassing physical and cognitive symptoms, resulting from smouldering pathological processes, which remain unmet therapeutic targets. We provide a consensus-based framework of possible pathological substrates and manifestations of smouldering MS, and we discuss clinical, radiological, and serum/cerebrospinal fluid biomarkers for potentially monitoring SAW. Finally, we share considerations for optimizing disease surveillance and implications for clinical trials to promote the integration of smouldering MS into routine practice and future research efforts. ANN NEUROL 2024.

Impact of nirsevimab immunization on RSV infections attended in the pediatric emergency department: First results in a tertiary hospital in Madrid.

INTRODUCTION: Human respiratory syncytial virus (RSV) is the most commonly identified virus associated with lower respiratory tract infections. The monoclonal antibody nirsevimab immunization campaign began in our country in October 2023. METHODS: This study was conducted in the Pediatric Emergency Department (PED) of a tertiary care center in Madrid, Spain. The aim was to compare PED visits of patients eligible for immunization with nirsevimab who attended between weeks 40 and 52 of 2022 and 2023 and who had a confirmed diagnosis of RSV infection. RESULTS: During the study period, 264 out of 765 patients with confirmed RSV infection who attended the PED were eligible for immunization with nirsevimab and were selected for our analysis. The PED attendance was 80.3% in 2022 and 19.7% in 2023. The number of RSV-positive cases increased from week 42 in both analyzed periods, with a peak of maximum incidence between weeks 46 and 48. In 2022, the morphology of the case curve in the group of children eligible for immunization was similar to the overall curve. However, in 2023, we did not observe a similar increase in cases among patients eligible for immunization. CONCLUSION: Immunization with nirsevimab during the 2023 RSV epidemic season had a beneficial effect, reducing the number of PED consultations for RSV infection.

Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer.

The prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) varies, being influenced by blood-related factors such as transcriptional profiling and immune cell ratios. We aimed to address the contribution of distinct whole blood immune cell components to the prognosis of these patients. This study analyzed pre-treatment blood samples from 152 chemotherapy-naive mCRPC patients participating in a phase 2 clinical trial (NCT02288936) and a validation cohort. We used CIBERSORT-X to quantify 22 immune cell types and assessed their prognostic significance using Kaplan-Meier and Cox regression analyses. Reduced CD8 T-cell proportions and elevated monocyte levels were substantially connected with a worse survival. High monocyte counts correlated with a median survival of 32.2 months versus 40.3 months for lower counts (HR: 1.96, 95% CI 1.11-3.45). Low CD8 T-cell levels were associated with a median survival of 31.8 months compared to 40.3 months for higher levels (HR: 1.97, 95% CI 1.11-3.5). These findings were consistent in both the trial and validation cohorts. Multivariate analysis further confirmed the independent prognostic value of CD8 T-cell counts. This study highlights the prognostic implications of specific blood immune cells, suggesting they could serve as biomarkers in mCRPC patient management and should be further explored in clinical trials.

Establishing Normal Serum Values of Neurofilament Light Chains and Glial Fibrillary Acidic Protein Considering the Effects of Age and Other Demographic Factors in Healthy Adults.

Multiple studies have shown the importance of blood-based biomarkers indicating axonal damage (serum neurofilament light chains [sNfL]) or astroglia activation (serum glial fibrillary acidic protein [sGFAP]) for monitoring different neurological diseases. However, normal values of these variables remain to be clearly defined, partly due to the influence of different demographic factors. We investigated demographic differences in a cohort of healthy volunteers. A cross-sectional study was conducted including 116 healthy controls with ages between 18 and 69 years (67.5% females; n = 79). sNfL and sGFAP concentrations were measured using single-molecule arrays. Age and body mass index affected sNfL values, and age was found to be the most important factor. The normal values changed with age, and we established normal values for individuals younger than 45 years as <10 pg/mL and for controls older than 45 years as <15 pg/mL. We established normal values at <10 pg/mL for individuals younger than 45 years and <15 pg/mL for older individuals. Alternatively, a Z-score of 1.5 was relevant for all controls. sGFAP was only affected by age. Differences in normal values were evident by 55 years. The highest normality limit for sGFAP was 140 pg/mL for controls under 55 years and 280 for older controls. We defined normal levels for sNfL and sGFAP and their corresponding age-associated changes. These data may contribute to the application of such variables in clinical practice.

Rheumatoid meningitis: a case series report and review of modern therapeutic schemes and outcome.

INTRODUCTION: Rheumatoid meningitis (RM) is an extremely rare extra-articular complication of rheumatoid arthritis (RA), with approximately 165 cases reported world-wide. RM exhibits a broad range of symptoms, with stroke-like episodes and seizures being the most common manifestations. The primary differential diagnoses include vascular and infectious diseases. The influence of immunomodulatory medications on the pathophysiology of RM remains unclear. There are no consensus guidelines on therapeutic regimen. METHODS: We present four patients with prior history of RA that developed different neurological syndromes in correlation to radiological leptomeningitis. Clinical presentations, comorbid conditions, supplementary diagnostic assessments, treatments, and prognosis are provided. A literature review of recent immunosuppressive management in RM patients was performed. RESULTS: Three patients presented to hospital with recurrent focal seizures. Only two suffered meningism, reporting headache and fever. Magnetic resonance imaging (MRI) showed different grades of leptomeningitis across all cases. Notably, three cases demonstrated bilateral involvement extending to the pachymeninges. Two patients exhibited pronounced CSF mononuclear inflammation while extended microbiological evaluations yielded negative results. Two patients required biopsy for confirmation. The initiation of immunosuppressive therapy marked a turning point for three patients who previously exhibited progressive deterioration. Mortality was absent in all cases. CONCLUSIONS: Our experience remarks the elusive nature of RM. Rigorous exclusionary diagnostics are imperative to differentiate RM from mimicking conditions. Clinical manifestations oscillate between transient episodes and progressive neurological impairments, punctuated by frequent epileptic seizures. In scenarios where clinical worsening persists or where clinical and radiological evaluations are inconclusive, aggressive immunosuppressive therapy is recommended.

The role of duty, gender and intergenerational care in grandmothers' parenting of grandchildren: a phenomenological qualitative study.

OBJECTIVES: The aim of this study was to describe grandmothers' experiences of taking care of their grandchildren in terms of their care-giving tasks, motivations and emotions. METHODS: A qualitative phenomenological study was conducted. Purposive sampling was used, based on the relevance of the research question. Seventeen participants were included, women ≥ 65 years old, grandmothers who care for their grandchildren at least 10 h per week and who attended the Nursing units of the Primary Care Health Centers (Madrid Public Health Service). Seventeen in-depth interviews were conducted. The interviews were audio-recorded, transcribed verbatim and thematic analysis was carried out from the perspective of hermeneutic phenomenology. For the analysis, the Excel program was used to organize and share the coding process. Also, we followed COREQ guidelines. RESULTS: Four main themes were identified: (a) Care out of obligation, where participants feel an obligation to help their children by caring for grandchildren, regardless of their number, and prefer to do so voluntarily; (b) Care out of responsibility, where grandmothers see their role as a responsibility that includes saving costs by caring for grandchildren and facilitating their children's work life balance; (c) Care as a social duty, reflecting a moral commitment inherited from their mothers to help future generations; and (d) Construction of care from a gender perspective, where grandmothers, as women, primarily assume the care and upbringing of grandchildren. DISCUSSION: Our results contribute to increase knowledge about childcare provided by grandmothers to their grandchildren. Grandmothers become fundamental pillars of families by helping their children balance family and work. Behind this care there is a strong sense of obligation, duty and generational responsibility. Grandmothers' help presents differences in the distribution of tasks and care by sex. Identifying factors that motivate grandmothers to care for their grandchildren helps nurses to perform higher quality comprehensive care.

Lobectomy in patients with differentiated thyroid cancer: experience of a Chilean tertiary center.

PURPOSE: Thyroid lobectomy (TL) is an appropriate treatment for up to 4 cm intrathyroidal differentiated thyroid cancer (DTC). There is scarce data regarding TL outside first-world centers. Our aim is to report a cohort of patients with DTC treated with TL in Chile. METHODS: We included DTC patients treated with TL, followed for at least 6 months, characterized their clinicopathological features and classified their risk of recurrence and response to treatment. RESULTS: Eighty-two patients followed for a median of 2.3 years (0.5-7.0). Seventy-three (89%) patients had papillary, 8 (9.8%) follicular and 1 (1.2%) high-grade DTC. The risk of recurrence was low in 56 (68.3%) and intermediate in 26 (31.7%). Eight (9.8%) patients required early completion thyroidectomy and radioiodine. At last follow-up, 52 (70.3%) had excellent, 19 (25.7%) had indeterminate, and 1 (1.4%) had structural incomplete response. CONCLUSION: In a developing country, TL is an adequate option for appropriately selected DTC patients.

Nanocellulose: The Ultimate Green Aqueous Dispersant for Nanomaterials.

Nanocellulose, a nanoscale derivative from renewable biomass sources, possesses remarkable colloidal properties in water, mechanical strength, and biocompatibility. It emerges as a promising bio-based dispersing agent for various nanomaterials in water. This mini-review explores the interaction between cellulose nanomaterials (nanocrystals or nanofibers) and water, elucidating how this may enable their potential as an eco-friendly dispersing agent. We explore the potential of nanocellulose derived from top-down processes, nanocrystals, and nanofibers for dispersing carbon nanomaterials, semiconducting oxide nanoparticles, and other nanomaterials in water. We also highlight its advantages over traditional methods by not only effectively dispersing those nanomaterials but also potentially eliminating the need for further chemical treatments or supporting stabilizers. This not only preserves the exceptional properties of nanomaterials in aqueous dispersion, but may even lead to the emergence of novel hybrid functionalities. Overall, this mini-review underscores the remarkable versatility of nanocellulose as a green dispersing agent for a variety of nanomaterials, inspiring further research to expand its potential to other nanomaterials and applications.

Seizures in Children With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Although respiratory symptoms are the most prominent manifestations of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and especially the omicron variant, may cause neurological manifestations such as seizures. It remains unclear if specific variants of the virus increase the risk of seizures more than others. MATERIAL AND METHODS: This was a retrospective multicenter study of pediatric (zero to 16 years) patients with COVID-19 who attended five pediatric emergency departments in Madrid, Spain, between March 2020 and July 2022. An analysis of demographics, medical history, and seizure characteristics was conducted. The data obtained were correlated with the incidence of the different strains of SARS-CoV-2 in the Community of Madrid. RESULTS: A total of 2411 seizures (infectious and noninfectious) were recorded, and 35 of them (1.4%) were positive for SARS-CoV-2. Of those 35 patients, 18 (51.4%) reported a history of previous seizures. The highest percentage of cases occurred when the omicron variant was the most prevalent (28 [80%] vs 7 [20%] before omicron variant). Typical febrile seizures accounted for 52.9% of the cases. No treatment was required in more than half (57.1%) of the cases. CONCLUSION: during the emergence of the omicron variant, there has been an increase in the number of COVID-19-associated seizures. These findings highlight the need for SARS-CoV-2 screening in patients with febrile and afebrile seizures, in addition to other microbiological, biochemical, or neuroimaging tests, depending on the patient's age and clinical presentation.

Impaired Quality of Life in Patients with Post-Surgical Hypoparathyroidism.

BACKGROUND: Hypoparathyroidism is characterized by chronic hypocalcemia with low or abnormal parathyroid hormone levels. Thyroid surgery remains a predominant cause of hypoparathyroidism, often preventable by partial thyroidectomy. Although hypoparathyroidism can impair quality of life (QOL), data remain limited for Latin America. We aimed to characterize clinical manifestations and QOL in patients with postsurgical hypoparathyroidism. METHODS: This case-control study included patients (>18 years) who underwent total thyroidectomy (TT) for differentiated thyroid cancer (DTC) with postsurgical hypoparathyroidism (Group 1, Cases) and those with DTC who underwent TT without postsurgical hypoparathyroidism (Group 2, Controls). Clinical records were collected, and the SF-36v2 QOL survey and a structured symptom survey were applied. A logistic multivariate regression analysis was performed. RESULTS: This study included 106 subjects (Group 1, N=41; Group 2, N=65). Group 1 patients were younger, had a higher frequency of lymph node resection, and more frequently received Ι-131 than Group 2 patients (p<0.05). In the SF-36v2 survey, Group 1 had fewer physical-functioning scores (odds ratio, 3.8; 95% confidence interval, 1.2-11.7) and lower scores in mental and physical components than Group 2 and national records. Commonly reported symptoms include paresthesia, daily fatigue, and memory alterations. Treatment adherence rates were 56% and 71% for calcium and calcitriol, respectively. Furthermore, 24% of patients experienced one or more hypoparathyroidism drug-related adverse effects. CONCLUSIONS: Patients with postsurgical hypoparathyroidism had an impaired QOL, a high frequency of disease-associated symptoms, and limited treatment adherence. These results should be considered when deciding the best surgical alternative for DTC.

Sedoanalgesia With Ketamine in the Emergency Department: Factors Associated With Unsatisfactory Effectiveness.

OBJECTIVE: Ketamine is a safe and widely used sedative and analgesic in children. The purpose of this study is to evaluate the response to sedoanalgesia for painful procedures in the pediatric emergency department. METHODS: A retrospective study was conducted in children younger than 16 years who underwent painful procedures with intravenous/intranasal ketamine between January 2016 and December 2022. We collected demographic variables, effectiveness, route of administration, indication, dose, sedation strategy, duration of procedure, and associated adverse effects. RESULTS: A total of 671 ketamine sedation procedures (411 males/260 females) were included, with a mean age of 7.2 years. Closed reduction was the most common painful procedure (53.8%), followed by burn healing (24.6%). Ketamine was administered intravenously in 93.4% of procedures and intranasally in 6.6%. The result of sedoanalgesia was satisfactory in 84.9% and unsatisfactory in 15.1%. The percentage of cases with unsatisfactory analgesia was higher with intranasal administration (36.4%; P < 0.001). In the intravenous group, the percentage of cases with unsatisfactory effectiveness (28.7%) was higher for patients younger than 2 years of age (P < 0.001). Arthrocentesis procedures were associated with the highest percentage of unsatisfactory sedoanalgesia failures among patients receiving intravenous ketamine (39.3%; P < 0.001). Intranasal ketamine patients who received a dose between 3.6 and 4 mg/kg had a significantly higher percentage of unsatisfactory sedoanalgesia (66.7%; P = 0.048). Patients receiving intravenous ketamine had significantly higher rates of unsatisfactory sedoanalgesia when the initial dose interval was 1.6 to 2 mg/kg (11.8%; P = 0.002) and when the final total dose was also 1.6 to 2 mg/kg (17.6%; P = 0.002). CONCLUSIONS: This study concludes that intravenous/intranasal ketamine can provide safe and successful analgesia in pediatric patients in the ED. At intravenous doses of 1-1.5 mg/kg, good effectiveness was achieved in almost 90% of cases. Arthrocentesis had the highest percentage of unsatisfactory results. Repeat dosing should be considered for procedures longer than 20 minutes.

In Vivo, In Vitro and In Silico Anticancer Activity of Ilama Leaves: An Edible and Medicinal Plant in Mexico.

Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin's lymphoma.

Active surveillance is a feasible and safe strategy in selected patients with papillary thyroid cancer and suspicious cervical lymph nodes detected after thyroidectomy.

Objective: After initial treatment, up to 30% of patients with papillary thyroid cancer (PTC) have incomplete response, mainly cervical lymph node (LN) disease. Previous studies have suggested that active surveillance (AS) is a possible option for these patients. Our aim was to report the results of AS in patients with PTC and cervical LN disease. Materials and methods: In this retrospective observational study, we included adult patients treated and followed for PTC, who presented with cervical LN disease and were managed with AS. Growth was defined as an increase ≥ 3mm in either diameter. Results: We included 32 patients: 27 (84.4%) women, age of 39 ± 14 years, all initially treated with total thyroidectomy, and 22 (69%) with therapeutic neck dissection. Cervical LN disease was diagnosed 1 year (0.3-12.6) after initial management, with a diameter of 9.0 mm (6.0-19.0). After a median AS of 4.3 years (0.6-14.1), 4 (12.5%) patients had LNgrowth: 2 (50%) of whom were surgically removed, 1 (25%) was effectively treated with radiotherapy, and 1 (25%) had a scheduled surgery. Tg increase was the only predictive factor of LN growth evaluated as both the delta Tg (p < 0.0366) and percentage of Tg change (p < 0.0140). None of the included patients died, had local complications due to LN growth or salvage therapy, or developed distant metastases during follow-up. Conclusion: In selected patients with PTC and suspicious cervical LNs diagnosed after initial treatment, AS is a feasible and safe strategy as it allows effective identification and treatment of the minority of patients who progress.

Impact of line probe assay-based molecular testing on individualized treatment in patients with rifampicin-resistant tuberculosis: data from the prospective INNOVA4TB cohort study in Ukraine.

BACKGROUND: Ukraine remains a high World Health Organization priority country for drug-resistant tuberculosis (TB). Rifampicin-resistant TB (RR-TB) has a more protracted, more complicated, and more expensive treatment. In 2021, Ukraine reported 4025 RR-TB cases - 5.4 times more (751) than all 30 European Union/ European Economic Area countries together. OBJECTIVES: The objective of the study was to determine the diagnostic accuracy of line probe assay (LPA), AID Autoimmun Diagnostika GmbH, for detecting resistance to anti-TB drugs and its clinical application for selecting treatment regimens. DESIGN: A prospective observational cohort study. METHODS: From May 2019 to June 2020, we consecutively enrolled patients with active TB hospitalized at the Regional Phthisiopulmonology Center (Vinnytsia, Ukraine), aged between 18 and 82 years. The LPA was performed in the Genetic Research Laboratory at National Pirogov Memorial Medical University, Vinnytsia, Ukraine. RESULTS: A total of 84 clinical specimens and 97 culture isolates from 126 TB patients were tested during the study. Accuracy (95% confidence interval) of LPA for clinical samples in comparison with phenotypic drug susceptibility test (DST) was 80.1 (68.5-89.0) for isoniazid (H), 74.7 (62.4-84.6) for rifampicin (R), 74.4 (62.5-84.1) for ethambutol, 71.4 (41.9-91.6) for streptomycin, 84.6 (62.4-96.5) for prothionamide/ethionamide, and 84.6 (73.6-92.3) for levofloxacin (Lfx), respectively. We found a significantly higher sensitivity of LPA for H, R, and Lfx for the culture isolates compared to clinical specimens (p < 0.05). LPA detected different mutations in 6 out of 17 (35.5%) patients susceptible to R by Xpert. A shorter treatment regimen with an injectable agent demonstrated a low suitability rate of 5% (8/156) in a cohort of RR-TB patients from Ukraine. CONCLUSION: Initial LPA testing accurately identifies resistance to anti-TB drugs and facilitates the selection of an appropriate treatment regimen, minimizing exposure to empirical therapy.

Study about the impact of rapid resistance detection on the treatment of patients with tuberculosis in Ukraine written by healthcare and biomedical professionals to better understand how we can improve the results of treatment and to prevent spreading of resistant bacteriaWhy was the study done? Ukraine has over 4000 patients with tuberculosis (TB) resistant to at least one drug (rifampicin) - five times that of all 30 European Union/European Economic Area countries combined. Unfortunately, only about 60% of such patients have been successfully treated in 2019. At that time, the majority of people suffering from tuberculosis in Ukraine, after checking resistance to rifampicin, initially received standard combinations of the first-line or second-line anti-TB medicines before the result of traditionally used tests (usually few weeks later) became available to individualize the treatment. Alternatively, the sputum could be transported to some overloaded reference laboratories located hundreds of km away from the treatment places.What did the researchers do? The INNOVA4TB team implemented rapid diagnostics of drug resistance in routine practice, guiding key antibiotics use in TB patients. A total of 181 samples from 126 individuals were tested during 2019-2020.What did the researchers find? This new diagnostic technology accurately detected resistance to 9 anti-TB drugs in sputum samples. It could be helpful to select appropriate TB treatment regimens, reducing time for decision from 1 month up to 2 days. Recommended at the study time 9-month shorter standardized treatment regimen with injectable agent was suitable only for 5% of patients for whom it was indicated in Vinnytsia region of Ukraine.What do the findings mean? The study has demonstrated successful implementation of the new molecular diagnostic technology from scratch in a country with restricted resources and limited TB laboratory capacity. This test can facilitate optimal distribution of available wards among patients with different profiles of resistance and correct choice between treatment options.

Pediatric Patients with Intracranial Arteriovenous Malformations: Trends in Emergency Room Presentation.

BACKGROUND: Pediatric intracranial arteriovenous malformation (AVM) patients are commonly admitted to the emergency room (ER). Increasing patient utilization of the ER has been associated with healthcare disparities and a trend of decreased efficiency. The aim of this study was to evaluate the trends of pediatric AVM ER admissions over recent years and identify factors associated with health care resource utilization and outcomes. METHODS: The 2016-2019 National Inpatient Sample was queried for patients under the age of 18 admitted with AVM. Cases of admission through the ER were identified. Demographic and severity factors associated with ER admission were explored using comparative and regression statistics. RESULTS: Of 3875 pediatric patients with AVM admitted between 2016 and 2019, 1280 (33.0%) were admitted via the ER. Patients admitted via the ER were more likely to be in the lowest median income category (P < 0.001), on Medicaid insurance (P = 0.008), or in the South (P < 0.001) than patients admitted otherwise. There was increased severity and increased rates of intracranial hemorrhage (ICH) in patients admitted via the ER (P < 0.001). Finally, there were increasing trends in ER admissions and ICH throughout the years. CONCLUSIONS: ER admission of pediatric AVM patients with ICH is increasing and is associated with a distinct socioeconomic profile and increased healthcare resource utilization. These findings may reflect decreased access to more advanced diagnostic modalities, primary care, and other important resources. Identifying populations with barriers to care is likely an important component of policy aimed at decreasing the risk of severe disease presentation.

Effect of BvAgNP on growth, development, and glyoxalase gene expression analysis in Mammillaria bombycina and Selenicereus undatus.

BACKGROUND: Silver nanoparticles (AgNPs) have been used in plant tissue culture as growth stimulants, promoting bud initiation, germination, and rooting. In prior studies, AgNPs were synthesized and characterized by green synthesis using extracts from Beta vulgaris var. cicla (BvAgNP), and their functionality as seed disinfectant and antimicrobial was verified. In this study, we evaluated the effect of BvAgNP on the growth and development of Mammillaria bombycina and Selenicereus undatus in vitro, as well as the expression of glyoxalase genes. METHODS: Explants from M. bombycina and S. undatus in vitro were treated with 25, 50, and 100 mg/L of BvAgNP. After 90 days, morphological characteristics were evaluated, and the expression of glyoxalase genes was analyzed by qPCR. RESULTS: All treatments inhibited rooting for M. bombycina and no bud initiation was observed. S. undatus, showed a maximum response in rooting and bud generation at 25 mg/L of BvAgNP. Scanning electron microscopy (SEM) results exhibited a higher number of vacuoles in stem cells treated with BvAgNP compared to the control for both species. Expression of glyoxalase genes in M. bombycina increased in all treatments, whereas it decreased for S. undatus, however, increasing in roots. CONCLUSIONS: This study presents the effects of BvAgNP on the growth and development of M. bombycina and S. undatus, with the aim of proposing treatments that promote in vitro rooting and bud initiation.