Hasil untuk "Diseases of the respiratory system"

Sun Young Kyung, Sung Hwan Jeong

Wenqiang He, Xueping Li, Haining Huang et al.

Abstract Objective Galectin-7, a β-galactoside-binding lectin involved in inflammation, immune regulation, and apoptosis, has been implicated in the development and progression of various lung diseases. Inflammation, immune dysregulation, and epithelial cell apoptosis are key pathophysiological mechanisms underlying chronic obstructive pulmonary disease (COPD). However, the clinical significance of galectin-7 in COPD remains unclear. This study aimed to investigate the association between sputum galectin-7 levels and the clinical characteristics and prognosis of patients with COPD. Methods In this prospective study, 150 patients with stable COPD and 50 healthy controls were enrolled. Demographic data, clinical parameters, and sputum samples were collected. Baseline galectin-7 concentrations in sputum supernatants were measured using an enzyme-linked immunosorbent assay (ELISA). Patients with COPD were followed for one year to document acute exacerbation events. Among COPD patients, Spearman correlation analysis and multivariable linear regression were performed to examine the associations between galectin-7 levels and clinical parameters or inflammatory markers, adjusting for sex, age, smoking status, and body mass index (BMI). Multivariable Poisson regression and logistic regression models were further applied to assess the relationship between galectin-7 levels and acute exacerbations within one year, with adjustment for the number of exacerbations in the previous year, sex, age, smoking status, BMI, and post-bronchodilator FEV1% predicted (Post-BD FEV1% pred). Results After adjustment in the analysis of covariance, galectin-7 levels were significantly lower in patients with GOLD III–IV than in healthy controls and patients with GOLD I–II (P < 0.05). Multivariable linear regression analyses indicated that galectin-7 levels were significantly associated with multiple clinical indicators and inflammatory markers. In the multivariable Poisson regression model, each 10 ng/mL increase in sputum galectin-7 was associated with a 15.7% reduction in the risk of acute exacerbations within one year (RR, 0.843; 95% CI, 0.716–0.973; P = 0.028). In the multivariable logistic regression model, each 10 ng/mL increase in sputum galectin-7 was associated with a 35.1% lower risk of frequent acute exacerbations within one year (OR, 0.649; 95% CI, 0.424–0.923; P = 0.029). Conclusion Lower sputum galectin-7 levels are associated with later stages and an increased risk of future acute exacerbations in COPD, suggesting that galectin-7 may be a promising biomarker related to disease severity and prognosis. Trial Registration This study was registered in the International Clinical Trials Registry (NCT03240315). Trial registration on July 31, 2017.

L.C. Ramsay, S.K. Brode, E. Rea et al.

BACKGROUND: Our objective was to estimate the attributable health care costs associated with TB in Ontario, Canada. METHODS: We conducted an incidence-based matched cohort study among individuals diagnosed with TB between April 1, 2002 to December 31, 2016. We matched exposed individuals 1:2 to unexposed individuals using hard and propensity score matching. Using phase-of-care costing, we calculated the mean attributable costs of TB, standardized to 10-day cost, for seven phases of illness: pre-diagnosis, initial treatment, continuation phase, remainder year 1, year 2, post-TB, and prior-to-death. We estimated survival-adjusted attributable mean 1-, 2-, and 5-year costs. RESULTS: We matched 6,456 individuals with TB to 12,443 individuals without TB. Mean (95% CI) attributable 10-day costs was highest in the pre-death phase at $2,656 ($2,207, $3,104), followed by the initial treatment phase at $1,693 ($1,608, $1,778). Hospitalization costs were the largest cost component in each phase. The mean attributable 1-, 2-, and 5-year survival-adjusted costs were $25,586, $30,178, and $33,370, respectively. CONCLUSION: Individuals with TB have higher health care costs over their lifetime (from pre-diagnosis until death) than individuals without TB.

Tomohiro Bando, Yumiko Sasaki, Wataru Koike et al.

ABSTRACT A 73‐year‐old male presented with an abnormal chest x‐ray revealing ground‐glass opacity (GGO) in the left lower lung field, accompanied by elevated KL‐6, SP‐D, and GM‐CSF antibody levels, indicative of autoimmune pulmonary alveolar proteinosis (PAP). Initial bronchoalveolar lavage and transbronchial lung biopsy revealed only nonspecific findings. During a CT‐guided needle aspiration biopsy (CT‐NAB), real‐time imaging showed that GGO gradually moved and shifted with positional changes. Although PAP is not fully confirmed yet due to a lack of pathological findings, this case highlights several clinical suggestions for patients with atypical lung shadows, including those with suspicion of PAP. Further, this is the first report of lung shadow mobility during CT‐NAB, emphasising the need for further studies to elucidate the pathophysiology of lung shadows and improve diagnostic accuracy.

Zongming Yang, Dong Xu, Xiuyun Zhou et al.

Abstract Background The impact of targeted next-generation sequencing (tNGS) in pediatric lower respiratory tract infections (LRTI) remains largely unknown. We aimed to investigate whether adding tNGS to standard conventional microbiological tests (CMTs), compared with CMTs alone, was associated with antimicrobial stewardship and clinical outcomes. Methods This retrospective cohort study was conducted at Tongji Hospital, Wuhan, between 2023-2024. Pediatric patients hospitalized with LRTI were categorized into tNGS (tNGS in addition to CMTs, typically as a second-line test) or control (CMTs alone) groups based on testing received during the first 4 days after admission. To address potential baseline confounding, we performed 1:2 propensity score matching to balance key clinical characteristics between groups. The primary outcomes were whether and time to provision of pathogen-directed treatment within 96 hours after the index time. Secondary outcomes included other antimicrobial stewardship measures and clinical outcomes. Between-group outcomes were assessed using generalized linear models to estimate risk differences (RDs, identity link) and odds ratios (ORs, logit link) for binary outcomes, while time-to-event analyses were performed using Fine-Gray subdistribution hazard models to account for competing risk of discharge, with results reported as hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Results After matching, 520 participants were included (182 tNGS group; 338 control group). During follow-up, 75 patients (41.21%) in the tNGS group and 48 (14.20%) in the control group received pathogen-directed treatment, with an absolute RD of 27.01% (95% CI: 18.95%, 35.07%) and an OR of 4.23 (95% CI: 2.78, 6.51). The mean time to treatment was 58.99 hours in the tNGS group vs. 82.95 hours in the control group (mean difference, −23.96 hours; 95% CI: −31.02, −16.90), with a corresponding HR of 3.55 (95% CI: 2.47, 5.09). Patients in the tNGS group also had lower rates of non-pathogen-directed antibiotic use (OR=0.52, 95% CI: 0.33, 0.79). Clinical outcomes were similar between the two groups. Conclusions Use of tNGS as a second-line test was associated with faster and more targeted antimicrobial treatment in pediatric LRTIs, but its impact on clinical outcomes requires further investigation. Clinical trial number Not applicable

Andrew Achaiah, Emily Fraser, Peter Saunders et al.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic condition. Serial FVC monitoring is most commonly used to assess progression of disease but FVC does not always reflect regional CT change in IPF. Recently there has been growing interest in quantitative CT (qCT) assessment of IPF. In this study, we compared different physiological and qCT measurements of disease progression in predicting mortality in IPF. Aims We question if a composite measure of disease progression using qCT and FVC is more predictive of mortality than individual measurements, and if addition of blood leukocyte levels further enhance predictive ability of these measurements of disease progression. Methods We conducted a retrospective analysis of an IPF cohort (n = 71). Annualised change (∆) in CT-measured lung volume (CTvol) and total lung fibrosis score (TLF) were calculated (using the computer software CALIPER) together with annualised change in FVC and blood leukocyte levels within 4 months of first CT. These were modelled against mortality using multivariate Cox regression. Concordance indexes (C-statistic) of different Cox regression models were used to determine the most predictive and discriminative combination for mortality. Results 65 cases (91.5%) were male. Median (IQR) age 73.6 years (68.4–79.3). Death was reported in 24 cases (33.8%). The median annualised change in (∆)FVC was − 4.4% (-9.6-0.0), ∆TLF; + 2.9% (0.2-7.0), and ∆CTvol; -4.3% (0.0-10.9). Combined measurements of disease progression (∆CTvol, ∆FVC and ∆TLF%) out-performed single-variable measurements in predicting all-cause mortality in IPF. The composite variable of [ΔFVC >10%, ΔCTvol >10% or ΔTLF% >10%] was most predictive of mortality [HR 7.14 (2.45–20.79), p <0.001]. Inclusion of blood leukocytes improved C-statistic scores for each multivariate model. Conclusion Composite end points of ∆CTvol, ∆FVC and ∆TLF% were more predictive of mortality than single-variable measurements in this cohort. Inclusion of blood leukocytes into risk stratification models further improved mortality prediction for all measures of disease progression.

Abdulla Baguneid, Thisarana Wijayaratne, Avinash Aujayeb et al.

Abstract An indwelling pleural catheter (IPC) is a valuable tool in the management of pleural effusions, allowing drainage strategies to be tailored to match patient-centred goals. Previously, IPCs were primarily utilised in malignant pleural effusion (MPE) in the presence of non-expandable lung (NEL) or after the failure of chemical pleurodesis. Several studies have compared IPC to intercostal chest drain (ICD) with talc pleurodesis (TP), as well as different drainage regimens, resulting in a transition of practice. Continued developments have led to novel adjuncts, such as digital drainage, which allow controlled flow rates. The emerging field of intrapleural therapy in MPE is gaining attention as a potential new treatment modality, possibly increasing the scope of IPCs further. This article will provide a narrative review of the role of IPCs and will be based on published evidence to date and highlight the importance of an individualised, patient-centred care approach.

Anthony J. Webster

There is a growing proportion of people with several disease conditions ("multimorbidity"), placing increasing demands on healthcare systems. One hypothesis is that clusters of diseases may arise from shared underlying disease processes (shared "pathogenesis"), whereby the presence of one disease indicates the state of disease progression to several related disease types. This article explains how this hypothesis can be tested using observational data for disease incidence. Specifically, a multistage model is used to test whether two diseases can have a "shared stage" or "step", before either disease can occur, and how the unobserved rate of this step can be determined. The approach offers a simple method for studying multiple diseases and identifying shared underlying causes of multiple conditions, and is illustrated with published data and numerical examples. The fundamental mathematical model is analysed to compare key statistical properties such as the expectation and variance with those of independent diseases. The main results do not need an understanding of the underlying mathematics and can be appreciated by a non-expert. Significance: It is widely believed that there are shared underlying pathways that can lead to several disease types (shared "pathogenesis"), and this may explain observed clusters of disease types. This article shows how this hypothesis can be tested for a pair or cluster of diseases, using observational data of disease incidence.

Bolin Liu, Alexander Fulton, Hector Zenil

Understanding disease relationships through blood biomarkers offers a pathway toward data driven taxonomy and precision medicine. We constructed a digital blood twin from 103 disease signatures comprising longitudinal hematological and biochemical analytes. Profiles were standardized into a unified disease analyte matrix, and pairwise Pearson correlations were computed to assess similarity. Hierarchical clustering revealed robust grouping of hematopoietic disorders, while metabolic, endocrine, and respiratory diseases were more heterogeneous, reflecting weaker cohesion. To evaluate structure, the tree was cut at a stringent threshold, yielding 16 groups. Enrichment of the largest heterogeneous cluster (Cluster 9) showed convergence on cytokine-signaling pathways, indicating shared immunological and inflammatory mechanisms across clinical boundaries. Dimensionality reduction with PCA and UMAP corroborated these results, consistently separating hematological diseases. Random Forest feature selection identified neutrophils, mean corpuscular volume, red blood cell count, and platelets as the most discriminative analytes, reinforcing hematopoietic markers as key drivers. Collectively, these findings show that blood-derived digital signatures can recover clinically meaningful clusters while revealing mechanistic overlaps across categories. The coherence of hematological diseases contrasts with the dispersion of systemic and metabolic disorders, underscoring both the promise and limits of blood-based classification. This framework highlights the potential of integrating routine laboratory data with computational methods to refine disease ontology, map comorbidities, and advance precision diagnostics.

Neslihan Edeer Karaca, Ayse Aygun, Tsvetelina Velikova

P. Jadhav, G. Boudoin, R. Miles et al.

BACKGROUND: The Wetmore Tuberculosis (TB) Clinic in New Orleans serves patients who often lack primary care (PC) or specialty care (SC), which is complicated by comorbidities. An initiative to provide on-site PC and coordinate care aims to enhance TB patient management. METHODS: Data collection involved categorizing patients based on their PC status: Group I (regular PC), Group II (intermittent PC), and Group III (no PC), with on-site Nurse Practitioner-based Bridge Care (NPBC) provided as needed. RESULTS: Over 12 months, 209 out of 354 patients required NPBC and PC/SC coordination, with a 20% shift from Group III to Group I, reducing the need for NPBC. CONCLUSION: The program improved TB care at Wetmore TB Clinic, offering a potential model for other TB clinics to enhance patient adherence and TB and post-TB treatment follow-up.

Alvin Kuo Jing Teo, Emily Lai-Ho MacLean, Greg J. Fox

Background: This scoping review aimed to characterise definitions used to describe subclinical tuberculosis (TB), estimate the prevalence in different populations and describe the clinical characteristics and treatment outcomes in the scientific literature. Methods: A systematic literature search was conducted using PubMed. We included studies published in English between January 1990 and August 2022 that defined “subclinical” or “asymptomatic” pulmonary TB disease, regardless of age, HIV status and comorbidities. We estimated the weighted pooled proportions of subclinical TB using a random-effects model by World Health Organization reported TB incidence, populations and settings. We also pooled the proportion of subclinical TB according to definitions described in published prevalence surveys. Results: We identified 29 prevalence surveys and 71 other studies. Prevalence survey data (2002–2022) using “absence of cough of any duration” criteria reported higher subclinical TB prevalence than those using the stricter “completely asymptomatic” threshold. Prevalence estimates overlap in studies using other symptoms and cough duration. Subclinical TB in studies was commonly defined as asymptomatic TB disease. Higher prevalence was reported in high TB burden areas, community settings and immunocompetent populations. People with subclinical TB showed less extensive radiographic abnormalities, higher treatment success rates and lower mortality, although studies were few. Conclusion: A substantial proportion of TB is subclinical. However, prevalence estimates were highly heterogeneous between settings. Most published studies incompletely characterised the phenotype of people with subclinical TB. Standardised definitions and diagnostic criteria are needed to characterise this phenotype. Further research is required to enhance case finding, screening, diagnostics and treatment options for subclinical TB.

Saikat Basu, Abir Malakar, Mohammad Mehedi Hasan Akash

Investigations on airborne transmission of pathogens constitute a rapidly expanding field, primarily focused on understanding the expulsion patterns of respiratory particulates from infected hosts and their dispersion in confined spaces. Largely overlooked has been the crucial role of fluid dynamics in guiding inhaled virus-laden particulates within the respiratory cavity, thereby directing the pathogens to the infection-prone upper airway sites. Here, we discuss a multi-scale approach for modeling the onset parameters of airway infection based on flow physics. The findings are backed by Large Eddy Simulations of inhaled airflow and computed trajectories of pathogen-bearing aerosols/droplets within two clinically healthy and anatomically realistic airway geometries reconstructed from computed tomography imaging. As a representative anisotropic pathogen that can transmit aerially, we have picked smallpox from the Poxviridae family to demonstrate the approach. The fluid dynamics findings on inhaled transmission trends are integrated with virological and epidemiological parameters for smallpox (e.g., viral concentration in host ejecta, physical properties of virions, and typical exposure durations) to establish the corresponding infectious dose (i.e., the number of virions potent enough to launch infection in an exposed subject) to be, at maximum, of the order of O(2), or more precisely 1 to 180. The projection agrees remarkably well with the known virological parameters for smallpox.

Zihan Wang, Daniel W. Yang, Zerui Liu et al.

This study presents the first implementation of multilayer neural networks on a memristor/CMOS integrated system on chip (SoC) to simultaneously detect multiple diseases. To overcome limitations in medical data, generative AI techniques are used to enhance the dataset, improving the classifier's robustness and diversity. The system achieves notable performance with low latency, high accuracy (91.82%), and energy efficiency, facilitated by end-to-end execution on a memristor-based SoC with ten 256x256 crossbar arrays and an integrated on-chip processor. This research showcases the transformative potential of memristive in-memory computing hardware in accelerating machine learning applications for medical diagnostics.

Hasan Mujtaba Buttar, Muhammad Mahboob Ur Rahman, Muhammad Wasim Nawaz et al.

This paper is the first to present a novel, non-contact method that utilizes orthogonal frequency division multiplexing (OFDM) signals (of frequency 5.23 GHz, emitted by a software defined radio) to radio-expose the pulmonary patients in order to differentiate between five prevalent respiratory diseases, i.e., Asthma, Chronic obstructive pulmonary disease (COPD), Interstitial lung disease (ILD), Pneumonia (PN), and Tuberculosis (TB). The fact that each pulmonary disease leads to a distinct breathing pattern, and thus modulates the OFDM signal in a different way, motivates us to acquire OFDM-Breathe dataset, first of its kind. It consists of 13,920 seconds of raw RF data (at 64 distinct OFDM frequencies) that we have acquired from a total of 116 subjects in a hospital setting (25 healthy control subjects, and 91 pulmonary patients). Among the 91 patients, 25 have Asthma, 25 have COPD, 25 have TB, 5 have ILD, and 11 have PN. We implement a number of machine and deep learning models in order to do lung disease classification using OFDM-Breathe dataset. The vanilla convolutional neural network outperforms all the models with an accuracy of 97%, and stands out in terms of precision, recall, and F1-score. The ablation study reveals that it is sufficient to radio-observe the human chest on seven different microwave frequencies only, in order to make a reliable diagnosis (with 96% accuracy) of the underlying lung disease. This corresponds to a sensing overhead that is merely 10.93% of the allocated bandwidth. This points to the feasibility of 6G integrated sensing and communication (ISAC) systems of future where 89.07% of bandwidth still remains available for information exchange amidst on-demand health sensing. Through 6G ISAC, this work provides a tool for mass screening for respiratory diseases (e.g., COVID-19) at public places.

Shams Nafisa Ali, Afia Zahin, Samiul Based Shuvo et al.

Cardiac auscultation, an integral tool in diagnosing cardiovascular diseases (CVDs), often relies on the subjective interpretation of clinicians, presenting a limitation in consistency and accuracy. Addressing this, we introduce the BUET Multi-disease Heart Sound (BMD-HS) dataset - a comprehensive and meticulously curated collection of heart sound recordings. This dataset, encompassing 864 recordings across five distinct classes of common heart sounds, represents a broad spectrum of valvular heart diseases, with a focus on diagnostically challenging cases. The standout feature of the BMD-HS dataset is its innovative multi-label annotation system, which captures a diverse range of diseases and unique disease states. This system significantly enhances the dataset's utility for developing advanced machine learning models in automated heart sound classification and diagnosis. By bridging the gap between traditional auscultation practices and contemporary data-driven diagnostic methods, the BMD-HS dataset is poised to revolutionize CVD diagnosis and management, providing an invaluable resource for the advancement of cardiac health research. The dataset is publicly available at this link: https://github.com/mHealthBuet/BMD-HS-Dataset.

Jonatan C. S. de Carvalho, P. V. da Silva-Neto, D. M. Toro et al.

COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell membranes are cleaved to produce platelet-activating factor (PAF), another lipid mediator. Nonetheless, the effect of GCs on this lipid pathway during COVID-19 therapy is still unknown. This is a cross-sectional study involving COVID-19 patients (n = 200) and healthy controls (n = 35). Target tandem mass spectrometry of plasma lipid mediators demonstrated that COVID-19 severity affected eCBs and PAF synthesis. This increased synthesis of eCB was adversely linked with systemic inflammatory markers IL-6 and sTREM-1 levels and neutrophil counts. The use of GCs altered these lipid pathways by reducing PAF and increasing 2-AG production. Corroborating this, transcriptome analysis of GC-treated patients blood leukocytes showed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression. Altogether, these findings offer a breakthrough in our understanding of COVID-19 pathophysiology, indicating that GCs may promote additional protective pharmacological effects by influencing the eCB and PAF pathways involved in the disease course.

A. Nogueira, Joaquim Barreto, F. Moura et al.

Background The escalating prevalence of type 2 diabetes (T2DM) poses an unparalleled economic catastrophe to developing countries. Cardiovascular diseases remain the primary source of costs among individuals with T2DM, incurring expenses for medications, hospitalizations, and surgical interventions. Compelling evidence suggests that the risk of cardiovascular outcomes can be reduced by three classes of glucose-lowering therapies (GLT), including SGLT2i, GLP-1A, and pioglitazone. However, an evidence-based and cost-effective protocol is still unavailable for many countries. The objective of the current study is to compare the effectiveness and cost-effectiveness of GLT in individuals with T2DM in Brazil. Methods We employed Bayesian Networks to calculate the incremental cost-effectiveness ratios (ICER), expressed in international dollars (Int$) per disease-adjusted life years [DALYs] averted. To determine the effectiveness of GLT, we conducted a systematic review with network meta-analysis (NMA) to provide insights for our model. Additionally, we obtained cardiovascular outcome incidence data from two real-world cohorts comprising 851 and 1337 patients in primary and secondary prevention, respectively. Our cost analysis took into account the perspective of the Brazilian public health system, and all values were converted to Int$. Results In the NMA, SGLT2i [HR: 0.81 (95% CI 0.69–0.96)], GLP-1A [HR: 0.79 (95% CI 0.67–0.94)], and pioglitazone [HR: 0.73 (95% CI 0.59–0.91)] demonstrated reduced relative risks of non-fatal cardiovascular events. In the context of primary prevention, pioglitazone yielded 0.2339 DALYs averted, with an ICER of Int$7,082 (95% CI 4,521–10,770) per DALY averted when compared to standard care. SGLT2i and GLP-1A also increased effectiveness, resulting in 0.261 and 0.259 DALYs averted, respectively, but with higher ICERs of Int$12,061 (95% CI: 7,227–18,121) and Int$29,119 (95% CI: 23,811–35,367) per DALY averted. In the secondary prevention scenario, all three classes of treatments were deemed cost-effective at a maximum willingness-to-pay threshold of Int$26,700. Notably, pioglitazone consistently exhibited the highest probability of being cost-effective in both scenarios. Conclusions In Brazil, pioglitazone presented a higher probability of being cost-effective both in primary and secondary prevention, followed by SGLT2i and GLP-1A. Our findings support the use of cost-effectiveness models to build optimized and hierarchical therapeutic strategy in the management of T2DM. Trial registration CRD42020194415.

A. Bahadori, B. Kuhlmann, D. Debray et al.

Background: Congenital portosystemic shunts (CPSS) are rare vascular anomalies resulting in communications between the portal venous system and the systemic venous circulation, affecting an estimated 30,000 to 50,000 live births. CPSS can present at any age as a multi-system disease of variable severity mimicking both common and rare pediatric conditions. Case presentations: Case A: A vascular malformation was identified in the liver of a 10-year-old girl with tall stature, advanced somatic maturation, insulin resistance with hyperinsulinemia, hyperandrogenemia and transient hematuria. Work-up also suggested elevated pulmonary pressures. Case B: A young girl with trisomy 8 mosaicism with a history of neonatal hypoglycemia, transient neonatal cholestasis and tall stature presented newly increased aminotransferase levels at 6 years of age. Case C: A 3-year-old boy with speech delay, tall stature and abdominal pain underwent abdominal ultrasound (US) showing multiple liver nodules, diagnosed as liver hemangiomas by hepatic magnetic resonance imaging (MRI). Management and outcome: After identification of a venous malformation on liver Doppler US, all three patients were referred to a specialized liver center for further work-up within 12 to 18 months from diagnosis. Angio-computed tomography (CT) scan confirmed the presence of either an intrahepatic or extrahepatic CPSS with multiples liver nodules. All three had a hyperintense signal in the globus pallidus on T1 weighted cerebral MRI. Right heart catheterization confirmed pulmonary hypertension in cases A and C. Shunts were closed either using an endovascular or surgical approach. Liver nodules were either surgically removed if there was a risk of malignant degeneration or closely monitored by serial imaging when benign. Conclusion: These cases illustrate most of the common chief complaints and manifestations of CPSS. Liver Doppler US is the key to diagnosis. Considering portosystemic shunts in the diagnostic work-up of a patient with unexplained endocrine, liver, gastro-intestinal, cardiovascular, hematological, renal or neurocognitive disorder is important as prompt referral to a specialized center may significantly impact patient outcome.

Fernanda Bruzadelli Paulino da Costa, Thaís Zamboni Berra, Jaqueline Garcia de Almeida Ballestero et al.

Introduction: Drug-resistant tuberculosis (DR-TB) is a global threat and a challenge for public health authorities worldwide. In children, the diagnosis is even more challenging and DR-TB is poorly described in the literature, as are its treatment outcomes. In this study, we aimed to describe the treatment of drug-resistant TB in children and young adolescents in Brazil. Methods: A descriptive epidemiological study of treatment for DR-TB in children under 15 years of age in Brazil between 2013 and 2020. The primary data source was the Information System for Special Tuberculosis Treatments (SITE-TB). Categorical variables were analyzed using relative frequencies (%) and continuous variables by measures of central tendency to characterize the profile of the cases, namely: sociodemographic, clinical characteristics, procedures, tests performed and treatment success. In order to verify the distribution of cases, a spatial analysis was carried out based on the municipality where the cases resided. Results: Between 2013 and 2020, 19,757 tuberculosis (TB) cases occurred in children aged <15 years in Brazil, and 46 cases of treatment for DR-TB were reported during the same period (annual average of 6 cases). Of these, 73.9% were aged 10–14, 65.2% were male, 4.3% were HIV+ and 43.3% were underweight (BMI<18.5) at the start of treatment. 17.4% had previous contact with TB, 69.6% had primary resistance, 47.8% multidrug resistance. The median duration of treatment was 15 months. DOT and standardized treatment regimen were performed in 52.2% of cases. Bacilloscopy was performed for 97.8% (57.8% positive); culture for 89.1% (75.6% positive), rapid molecular test for 73.9% with proven resistance to rifampicin in 55.8%. Susceptibility testing revealed resistance mainly to isoniazid (87.8%) and rifampicin (60.6%). 73.9% of cases were successfully treated and one death was reported. Cases were treated in 26 Brazilian municipalities, with the majority in Rio de Janeiro (15) and São Paulo (4). Conclusion: DR-TB treatment was recorded in <1% of general TB cases in children and young adolescents, suggesting underreporting of drug-resistant cases in the country. Despite the low number of registered cases, the data reflect the situation of DR-TB in this population and describe important aspects of the problem, as the child needs comprehensive, individualized care, with support from different professionals. We recommend a strengthening of the country's referral services for the care of children with DR-TB so that surveillance and health care services can work together to identify and follow up cases.