Search Results (70)

Pediatric tuberculosis (TB) remains diagnostically challenging because of nonspecific presentations and the frequent absence of microbiological confirmation. We aimed to characterize pediatric TB patients presenting to a non-specialized tertiary hospital in Romania and to explore factors associated with bacteriological confirmation. We retrospectively analyzed children diagnosed with TB between 2017 and 2025 at a tertiary pediatric hospital in Bucharest. Clinical, epidemiological, laboratory, radiological, microbiological, and follow-up data were evaluated. Factors associated with bacteriological confirmation were assessed using univariate and exploratory multivariable analyses. Among 48 patients, the median age was 14 years (IQR 8.25–16), and 37.5% of cases were bacteriologically confirmed. Initial presentations were pleural effusion (47.9%), pneumonia (41.7%), and cavitary disease (10.4%). No patient with pleural effusion had a documented TB contact, compared with 45.0% with pneumonia and 40.0% with cavitary disease (p < 0.001). Bacteriologically confirmed patients were older and more frequently had cavitary lesions. In exploratory Firth penalized logistic regression, older age and the presence of cavitary lesions remained associated with bacteriological confirmation. Pediatric TB may mimic common respiratory diseases even without known TB contact. In exploratory Firth penalized logistic regression, older age and cavitary lesions were associated with bacteriological confirmation, although the estimates, particularly for cavitary lesions, were imprecise and should be interpreted cautiously, while the substantial proportion of clinically diagnosed cases highlights the importance of integrating clinical, radiological, immunological, and microbiological findings. Full article

Background: While non-specific pleural empyema in children can be successfully managed with conservative drainage and thoracentesis in 80–84% of cases, tuberculous pleural empyema (TB empyema) exhibits high resistance and frequently requires extensive thoracic surgery. The choice of surgical scope depends directly on disease stage and secondary complications. Methods: We conducted a retrospective cohort study of 85 pediatric patients (aged 4 to 17 years) with confirmed TB empyema treated between 1984 and 2022, and followed until 2025. Disease staging followed a predefined adaptation of the American Association for Thoracic Surgery (AATS) consensus classification. The study adhered strictly to STROBE guidelines, incorporating temporal stratification across three historical eras and standardized Clavien–Dindo complication reporting. This study describes a 38-year surgical experience at a tertiary pediatric phthisiosurgical center; non-operated patients successfully cured with exclusive chemotherapy were excluded. Results: Stage I empyema was identified in three patients, Stage II in seven, and Stage III in 75 patients (79 total procedures). Stage I–II patients underwent video-assisted thoracoscopic (VATS) debridement. In Stage III, advanced reconstructive interventions were required (39 VATS pleurectomies, 21 segmental resections, eight pleuropneumonectomies, six lobectomies, two thoracomyoplasties, two open resections, and one bronchus occlusion). Postoperative complications occurred in two patients (2.35% patient-level; categorized as Clavien–Dindo Grade IIIa and Grade IIIb), presenting as delayed lung re-expansion managed via secondary minor interventions. Overall 30-day postoperative mortality was 0.0%. Over a median follow-up of 48 months (database lock: 31 December 2025; 97.65% 36-month completeness), zero disease recurrences were documented (0.0%). Conclusion: In this tertiary surgical cohort, combined management incorporating stage-dependent surgical intervention achieved durable clinical cure. Early VATS debridement represents an effective option for Stage I–II patients who fail initial drainage, potentially reducing progression to a rigid fibrothorax and the subsequent need for extensive pulmonary resections. Full article

Pott’s disease, also known as tuberculous spondylodiscitis, accounts for 50% of all forms of skeletal tuberculosis. It is rare in children, especially in low-burden TB countries. We present a case of Pott’s disease with miliary tuberculosis in a 22-month-old child. Furthermore, we provide an exploratory literature review of pediatric cases published in PubMed and Scopus between January 2000 and August 2025, including patients aged 0 to 17 years with confirmed or clinically diagnosed tuberculous spondylodiscitis. Sixty-four cases were included. Most cases (81.3%) involved children from highly endemic countries, particularly India. Median age was 10 years, with a median diagnostic delay of 141.4 days. The most common signs and symptoms were back pain (79.6%), followed by difficulty walking (68.4%). The thoracic spine was the most affected segment (60.3%). Sixty-three received anti-TB therapy, 58% required surgical intervention, and treatment led to overall clinical recovery in 96.9% of cases. Neurological deficits were reported in 46% (paresthesia) and 68.4% (motor weakness), with permanent motor sequelae in 8.1% and persistent spinal deformity (kyphosis) in 14.5%. Our case highlights the importance of considering the suspicion of tuberculous spondylodiscitis, even in low-endemic countries, to achieve early diagnosis and appropriate therapeutic management. Early MRI combined with microbiological confirmation is essential to reduce the risk of severe complications, including neurological sequelae, progressive spinal deformities, and potentially life-threatening outcomes in growing patients. Full article

Background/Objectives: Children account for ∼11% of global TB cases. Adequate nutrition improves risk prediction, treatment outcomes, and helps identify children for TB-preventive treatment. We aimed to identify current evidence on food intake and nutrition, compare it with guidelines, and describe how nutrition is integrated into care for children with pulmonary TB. Methods: We a scoping review adhering to Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) of peer-reviewed and gray literature from January 2013 to March 2026. Results: We found limited evidence: 16 research articles, six supplementary records, and two guideline documents. Evidence on nutrition in pediatric pulmonary TB remains insufficient. Many studies included nutritional status in clinical assessment. Few studies examined household food assistance. Conclusions: Rigorous studies are needed to build evidence and translate it into practice to improve outcomes and prevent malnutrition in children with pulmonary TB. Full article

Background/Objectives: Children with autoimmune gastrointestinal diseases are at increased risk of impaired bone health due to chronic inflammation, nutritional deficiencies, growth disturbances, and treatment-related factors. While dual-energy X-ray absorptiometry (DXA) is the standard method for assessing bone mineral density (BMD), it provides limited information on bone microarchitecture. The trabecular bone score (TBS), derived from lumbar spine DXA images, has emerged as a complementary marker of bone quality. This study aimed to evaluate bone mass and TBS in children with autoimmune gastrointestinal diseases and to assess the clinical utility of TBS in comparison with children with a history of fractures and healthy controls. Methods: This study included 152 children aged 5–18 years: 45 with autoimmune gastrointestinal diseases (Crohn’s disease, ulcerative colitis, or celiac disease), 37 with a history of fractures, and 70 healthy controls. Anthropometric measurements, serum 25-hydroxyvitamin D [25(OH)D] concentrations, DXA-derived parameters, and TBS values were analyzed. Bone mineral density was assessed at the lumbar spine and total body less head (TBLH), with additional adjustment for height-for-age Z-score (HAZ). TBS values were expressed as sex- and pubertal stage-adjusted Z-scores. Results: Low bone mass (aBMD_{for age} Z-score ≤ −2) was observed in 30.3% of participants at TBLH and 11.1% at the lumbar spine, whereas a TBS Z-score ≤ −2 was identified in 5.2% of children. No significant differences in TBS or TBS Z-scores were found among the study groups. In multivariable analysis, fracture history was independently associated with lower absolute TBS, whereas no independent predictors of TBS Z-score were identified. Children with fractures had significantly lower HAZ-adjusted lumbar spine aBMD Z-scores than children with autoimmune gastrointestinal diseases and controls. TBS Z-scores correlated positively with age-adjusted and HAZ-adjusted aBMD values but showed no association with BMI or serum 25(OH)D concentrations. Conclusions: In this cross-sectional study, TBS did not distinguish children with autoimmune gastrointestinal diseases from those with fractures or healthy controls in the unadjusted analyses. Although TBS was associated with selected DXA-derived measures of bone mineral density and fracture history was independently associated with lower absolute TBS after multivariable adjustment, no independent predictors of TBS Z-score were identified. These findings suggest that the clinical role of TBS in the assessment of pediatric bone health remains to be established. Larger prospective studies are crucial to determine whether TBS provides clinically meaningful information complementary to conventional DXA for the assessment of skeletal health and fracture risk in children. Larger prospective studies are needed to clarify the clinical value of TBS for fracture risk assessment in pediatric autoimmune gastrointestinal diseases. Full article

Distinguishing tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) remains difficult when presentation is non-specific, blood cultures are negative, or initial biopsy is non-diagnostic. The two entities differ substantially in antimicrobial strategies, resistance testing requirements, public health interventions, and surgical thresholds, yet diagnostic delay is associated with neurological deficits, spinal instability, and permanent deformity. This narrative review maps the non-imaging evidence most useful for frontline differentiation between TS and PS across five domains: epidemiology and risk stratification, clinical presentation, laboratory markers, tissue acquisition and histopathology, and molecular diagnostics. PubMed/MEDLINE was searched from inception to 31 March 2026 using pre-specified Boolean search terms; a secondary Scopus search identified no additional eligible records. Following screening, approximately 90 records were included in this synthesis. Priority was given to comparative TS-versus-PS cohorts, biopsy-yield and culture-negative studies, pathology series, pediatric data, and recent molecular diagnostics literature. Epidemiological TB (tuberculosis) risk, longer symptom duration, constitutional symptoms, deformity, and a less intense acute-phase response increase the probability of TS, whereas healthcare exposure, bacteraemia, recent spinal procedures, and brisk neutrophilic inflammation favor PS. In stable patients, the highest-yield strategy is early blood cultures followed by image-guided biopsy with parallel tissue allocation for bacterial culture, mycobacterial studies, histopathology, and selected molecular assays. No single laboratory marker reliably distinguishes TS from PS without tissue confirmation. Per a 2023 systematic review and meta-analysis, image-guided percutaneous biopsy achieves microbiological confirmation in approximately one-third of cases. Histopathology demonstrating caseating granulomatous inflammation supports TS, although a substantial minority of confirmed cases lack classic features. Supported by cohort prospective data, Xpert MTB/RIF Ultra has the clearest first-line molecular role when TS is plausible and should be requested at the time of first biopsy rather than reserved for salvage testing; broader or targeted next-generation sequencing is best reserved for selected unresolved cases. Imaging differentiation is addressed in the companion manuscript, Part II. Full article

Using Global Burden of Disease 2021 modeled estimates, we assessed the burden, temporal trends, and inequalities of pediatric all-form tuberculosis (TB) and multidrug-resistant TB (MDR-TB) from 1990 to 2021 across 204 countries and territories. Compared with all-form TB, pediatric MDR-TB showed a distinct and less favorable estimated trajectory. Although GBD-based estimates suggested overall declines in pediatric all-form TB incidence and mortality, the MDR-to-all-form ratio increased worldwide for both incidence and mortality, suggesting a growing proportional contribution of MDR-TB within the estimated pediatric TB burden. In 2021, pediatric MDR-TB remained concentrated in low- and low–middle-SDI settings, where modeled socioeconomic inequalities appeared to become more pronounced over time. Mortality relative to incidence was highest among children aged under 5 years, with particularly elevated and imprecise mortality-to-incidence ratios for MDR-TB. Sex disparities also evolved differently by disease type: they generally narrowed for all-form TB but were more heterogeneous and in some settings widened for MDR-TB. These GBD-based findings suggest that progress in overall pediatric TB control may not have translated evenly to drug-resistant disease and highlight the need for pediatric TB strategies that explicitly address drug resistance, early childhood vulnerability, and inequitable access to diagnosis and treatment. Due to the sparsity of global pediatric data, no independent external validation was performed; findings are based on internal sensitivity analyses of GBD estimates. Full article

Background: Accurate presurgical localization of eloquent cortex and subcortical pathways is essential in neurosurgery, guiding the balance between maximal safe resection and preservation of neurological function. This narrative review compares the clinical utility of task-based functional magnetic resonance imaging (tb-fMRI) and resting-state functional magnetic resonance imaging (rs-fMRI) in neurosurgical populations, with emphasis on brain tumors and epilepsy. Methods: This narrative review was based on a non-systematic literature search of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar from database inception to March 2026. The review focused on tb-fMRI and rs-fMRI for presurgical functional mapping in neurosurgical populations, including clinical utility, feasibility, validation, limitations, and workflow integration. Results: Tb-fMRI remains the most established noninvasive modality for motor and language mapping and language lateralization because of its task-specific activation maps and established role in clinical workflows. However, its use is limited by dependence on patient cooperation, task performance, and intact neurovascular coupling; thus, aphasia, cognitive impairment, fatigue, paresis, pediatric age, sedation, and tumor-related neurovascular uncoupling may render tb-fMRI inconclusive or misleading. Rs-fMRI offers a task-free alternative based on intrinsic functional connectivity, enabling simultaneous mapping of multiple resting-state networks from a single acquisition and providing particular value in non-cooperative, cognitively impaired, aphasic, pediatric, or sedated patients. Evidence indicates that rs-fMRI is most robust for sensorimotor mapping, with reported agreement with tb-fMRI and intraoperative direct electrical stimulation, whereas language mapping remains less consistent and more dependent on analytical methodology. Neither modality replaces intraoperative stimulation, which remains the reference standard. Conclusions: Current evidence supports a multimodal presurgical strategy in which tb-fMRI is used first-line in cooperative patients; rs-fMRI is added when task-based mapping is limited or infeasible, and both are interpreted alongside tractography, neuronavigation, and intraoperative mapping. Full article

Background: Pediatric tuberculosis (TB) remains a major global health concern, accounting for a substantial proportion of TB-related morbidity and mortality worldwide. Treatment in children is particularly challenging due to age-specific pharmacokinetics, difficulties in drug administration, poor palatability, and reliance on caregivers for adherence. Objectives: This narrative review aims to evaluate the advantages and limitations of fixed-dose combinations (FDCs) in the treatment of pediatric TB, with a focus on adherence, pharmacological considerations, clinical outcomes, and implementation challenges. Methods: A narrative review of the literature was conducted, including clinical studies, pharmacokinetic analyses, programmatic data, and international guidelines related to the use of FDCs in pediatric TB management. Results: Evidence indicates that pediatric FDCs significantly improve treatment adherence by reducing pill burden and simplifying dosing regimens. They also decrease the risk of medication errors and inadvertent monotherapy, thereby contributing to the prevention of drug resistance. The availability of dispersible, child-friendly formulations has enhanced acceptability and ease of administration. However, limitations persist, including reduced flexibility in dose individualization, challenges in identifying the causative agent in adverse drug reactions, and variable access across settings. Pharmacokinetic concerns, particularly regarding rifampicin exposure, have been addressed in newer WHO-recommended formulations. Conclusions: FDCs represent a critical advancement in pediatric TB management and are strongly supported by international guidelines. Further research is needed to optimize formulations, ensure equitable access, and evaluate long-term clinical outcomes in diverse pediatric populations. Full article

Background: Conjugated hyperbilirubinemia in early infancy is a critical indicator of hepatobiliary dysfunction. Prompt and accurate identification is essential to diagnose cholestatic liver disease (CLD), particularly biliary atresia. Current guidelines define conjugated bilirubin (CB) ≥ 1 mg/dL as abnormal, irrespective of total bilirubin (TB). This study aimed to evaluate whether combining absolute and relative CB thresholds improves diagnostic performance for CLD. Methods: We retrospectively analyzed all infants aged ≤6 months of chronological age with CB ≥ 1 mg/dL admitted to the Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria, between January 2004 and February 2025. During that period, 116,104 infants were born at our hospital catchment area; 3119 of these underwent bilirubin fractionation, and 257 infants (0.2% of total births) had a CB ≥ 1 mg/dL and were included in the analysis. Clinical and biochemical data were extracted. Diagnostic performance of the absolute (CB ≥ 1 mg/dL) and in combination with the relative (CB ≥ 20% of TB) thresholds was assessed using receiver operating characteristic (ROC) analysis for the detection of CLD. Results: Among 257 infants, 47 (18%) were diagnosed with CLD. The median age at the time of blood sampling was 18 days (IQR 9–31). The combined criterion (CB ≥ 1 mg/dL and ≥20% of TB) achieved 100% sensitivity and 61.2% specificity (AUC = 0.82, 95% CI 0.79–0.92; p < 0.001). Implementation of the combined cut-off reduced the number needed to screen from 5.5 to 2.7, representing nearly a twofold improvement in diagnostic efficiency. Conclusions: Applying both absolute (≥1 mg/dL) and relative (≥20% of total bilirubin) CB thresholds substantially improves detection of neonatal CLD in early infancy. This combined approach maintains full sensitivity while reducing false positives and unnecessary investigations, thereby enhancing diagnostic efficiency in early infancy. Full article

Background: Tuberculosis (TB) remains a major cause of morbidity and mortality among children worldwide, with approximately one million new pediatric cases annually. The conventional treatment for drug-susceptible TB has long relied on a 6-month multidrug regimen, which is highly effective but associated with challenges in adherence, toxicity, and healthcare burden. Objectives: To evaluate whether short-course therapy is an appropriate regimen for children and young adolescents with drug-susceptible TB, with particular focus on its efficacy, safety, and applicability in different clinical contexts. Methods: A structured narrative review of the literature was conducted, including randomized controlled trials, observational studies, and international guidelines addressing treatment duration in children and young adolescents with drug-susceptible TB. Evidence was synthesized focusing on children and young adolescents <16 years with drug-susceptible TB treated with short-course regimens compared to standard therapy. Results: A shorter treatment regimen, particularly 4-month courses, has been investigated as an alternative to standard therapy in the pediatric population with drug-susceptible TB. Children often present with paucibacillary and non-severe forms of TB, providing a biological rationale for treatment shortening. Evidence from a randomized controlled trial has demonstrated that a 4-month regimen is non-inferior to the standard 6-month therapy in children and young adolescents with non-severe, drug-susceptible TB. These findings have informed recent international guideline updates, which now recommend short therapy in carefully selected patients. However, a short regimen is not appropriate for infants younger than 3 months, children with severe or complicated TB, extrapulmonary disease such as central nervous system involvement, or those with drug-resistant TB. The overall quality of evidence remains moderate, and long-term relapse data are still emerging. Conclusions: Short-course therapy represents a promising but selective strategy in pediatric drug-susceptible TB management. It offers potential advantages, including improved adherence, reduced drug toxicity, and lower healthcare costs. However, its safe implementation requires accurate patient selection, access to appropriate diagnostic tools, and structured follow-up. Careful application within clearly defined clinical criteria is essential to ensure optimal outcomes. Full article

Background: Tuberculosis (TB) in children is associated not only with infectious burden but also with potential psychological distress, which remains insufficiently explored. The aim of this study was to evaluate the pattern and evolution of depressive symptoms in pediatric TB patients during treatment using a structured screening approach. Methods: We conducted a retrospective observational study including 190 pediatric patients aged 7–18 years diagnosed with tuberculosis between 2019 and 2021. Depressive symptoms were assessed at two time points, namely at diagnosis (T0) and at first follow-up (T1), using a 10-item structured clinical screening tool routinely applied in practice. A threshold of ≥50% affirmative responses was used to identify patients with suspected depressive symptoms. The Children’s Depression Inventory (CDI) was administered to patients with positive screening results, according to standard clinical protocols. Descriptive and comparative analyses were performed to evaluate changes over time. Results: A high proportion of patients screened positive for depressive symptoms at baseline (T0). At follow-up (T1), a reduction in the proportion of patients with suspected depressive symptoms was observed; however, a substantial number of patients continued to report symptoms suggestive of emotional distress. Most symptom changes between T0 and T1 were not statistically significant, with the exception of decreased appetite, which showed a modest improvement. The overall pattern suggests persistence of symptoms in a subset of patients over time. Conclusions: These findings suggest that symptoms indicative of psychological distress are common among pediatric TB patients and may persist during treatment. However, given the use of a non-validated screening tool and the retrospective design, the results should be interpreted with caution. The study highlights the potential value of systematic psychological assessment in this population and supports the need for further research using validated instruments. Full article

Central nervous system tuberculosis (CNS-TB) is a severe extrapulmonary manifestation of tuberculosis associated with high morbidity and mortality, particularly in children. While tuberculous meningitis remains the predominant form, focal parenchymal lesions such as tuberculomas and abscesses are less common. Cerebellar tuberculomas represent an exceptionally rare localization and may mimic posterior fossa tumors, leading to diagnostic delay. This article provides an updated review of CNS tuberculosis with special emphasis on pediatric epidemiology and cerebellar involvement, and presents a clinical case of surgically treated cerebellar tuberculoma. This clinical case demonstrates the difficulties in differential diagnosis of cerebellar tuberculosis from a tumor in this location. Full article

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide, with children representing a particularly vulnerable population in whom diagnosis is often challenging. Pediatric TB is typically paucibacillary and presents with non-specific clinical manifestations, limiting the sensitivity of microbiological confirmation and increasing reliance on immunological tests. The Tuberculin Skin Test (TST) and Interferon-Gamma Release Assays (IGRAs) are the most widely used tools for detecting Mycobacterium tuberculosis infection, yet both have important limitations, especially in young children and in Bacillus Calmette–Guérin (BCG)-vaccinated populations. TST lacks specificity due to cross-reactivity with BCG and environmental mycobacteria, while IGRAs, although more specific, require laboratory infrastructure and may have reduced sensitivity in early childhood. The Tuberculosis Skin Test (TBST), based on M. tuberculosis-specific antigens such as ESAT-6 and CFP-10, has emerged as a promising alternative that combines the operational simplicity of TST with the antigenic specificity of IGRA. This paper reviews the immunological principles, diagnostic performance, and practical considerations of TBST in pediatric populations, with direct comparison to TST and IGRA. Evidence from recent studies suggests that TBST may offer improved specificity over TST, with broadly comparable diagnostic accuracy to IGRA in some settings, although findings are not fully consistent across studies. Particular attention is given to its performance in BCG-vaccinated children and, based on emerging evidence, in those under five years of age. The potential role of TBST in clinical algorithms and public health strategies is discussed, along with current evidence gaps and future research priorities. Full article

Tuberculosis (TB) remains a major global cause of morbidity and mortality. Current tools for monitoring treatment response rely on sputum-based microscopy and culture, which are often insensitive, time-consuming, and impractical in extrapulmonary or pediatric TB and in individuals unable to produce sputum. Metabolomics has emerged as a promising approach for identifying host-derived biomarkers that reflect treatment-associated immunometabolic changes; however, the available evidence remains heterogeneous and has not been comprehensively synthesized. We conducted a comprehensive literature review of human studies evaluating metabolomic biomarkers in relation to TB treatment response or outcomes. PubMed, Scopus, and EMBASE were searched for human studies evaluating targeted or untargeted metabolomics (NMR, LC-MS, GC-MS, CE-MS) in relation to treatment response or outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using QUIPS and PROBAST. Findings were synthesized using a structured framework organized across treatment stages and outcomes. Of 218 records identified, 139 titles and abstracts were screened and 42 full texts assessed; 15 studies met the inclusion criteria. Recurrent treatment-associated signals involved amino acid metabolism, particularly the tryptophan–kynurenine pathway, as well as vitamin and cofactor metabolites (pyridoxate, nicotinamide, trigonelline). Plasma studies frequently reported lipid remodeling and bile acid perturbations, whereas urine studies highlighted polyamine metabolism (e.g., N¹,N¹²-diacetylspermine) and fatty acid β-oxidation markers. Common limitations included inadequate adjustment for confounders and, in prediction models, small sample sizes and limited external validation. Metabolomics reveals reproducible but heterogeneous immunometabolic changes during TB therapy. Key pathways include tryptophan–kynurenine metabolism, vitamin and cofactor metabolism, lipid remodeling, and urine polyamine pathways. Standardization and prospective multicenter validation are needed for clinical translation. Full article