COVID-19 has been linked to musculoskeletal complications, including femoral head avascular necrosis (AVN). Both COVID-19-related hypercoagulability and corticosteroid therapy have been proposed as contributing factors. This systematic review synthesizes current evidence on the occurrence, clinical characteristics, timing, and risk factors for femoral head AVN following COVID-19.

A PRISMA-compliant systematic search of PubMed, Embase, and Scopus identified observational studies and case series (≥10 patients) reporting femoral head AVN in adults or adolescents with confirmed COVID-19. Data on epidemiology, symptom onset, imaging findings, and corticosteroid exposure were narratively synthesized due to heterogeneity.

Fifteen eligible studies described patients with post-COVID femoral head AVN. Symptom onset ranged from days to >12 months after infection. Early MRI often revealed asymptomatic or low-grade disease. Corticosteroid exposure was common and strongly associated with AVN severity; however, several studies reported AVN in patients without steroid use, whether this reflects an independent contribution of COVID-19 or unrecognized confounding cannot be determined from the available uncontrolled data. Higher cumulative steroid doses, severe pulmonary involvement, and elevated inflammatory markers were consistently linked to more advanced AVN stages.

Femoral head AVN is an emerging post-COVID complication with variable timing and presentation. Corticosteroid exposure remains the principal risk factor; whether COVID-19 contributes independently of corticosteroids is unproven, and current evidence supports an association rather than a causal relationship. Awareness of this potential complication is warranted, although the role of early MRI screening remains to be established in prospective studies.

Background: The COVID-19 pandemic disrupted healthcare systems and antimicrobial stewardship, potentially altering antimicrobial resistance patterns. This study characterized temporal changes in the proportions of multidrug-resistant organisms (MDROs) and identified associated factors before and during the pandemic at a tertiary care hospital in northeastern Thailand. Methods: A single-center retrospective observational study was conducted at Roi Et Hospital, including 5458 culture-confirmed MDRO cases (2017-2022), stratified into pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Pathogen-specific resistance proportions were compared using odds ratios (ORs) with 95% confidence intervals (CIs). Multivariable logistic regression identified independently associated factors within each period. Results: The proportion of MDRO cases classified as hospital-acquired increased from 40.71% to 57.41% (p < 0.001). Carbapenem-resistant Acinetobacter baumannii (CRAB) increased markedly (22.87% to 76.11%; OR 10.75, 95% CI 9.43-12.26), followed by carbapenem-resistant Enterobacterales (CRE) (4.05% to 21.61%; OR 6.54, 95% CI 5.84-7.32) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) (14.32% to 27.15%; OR 2.23, 95% CI 1.87-2.65; all p < 0.001). Vancomycin-resistant Enterococcus (VRE) declined significantly (OR 0.41, 95% CI 0.25-0.68; p < 0.001). Methicillin-resistant Staphylococcus aureus (MRSA) showed a higher proportion among clinical isolates (3.28% to 6.34%; OR 2.01, 95% CI 1.42-2.83), although without a consistent annual trend. In multivariable analyses, ICU admission was independently associated with lower odds of CRE (aOR 0.52) and CRPA (aOR 0.63) and with higher odds of CRAB (aOR 2.13; all p < 0.001). Conclusions: The COVID-19 pandemic was associated with a major proportional shift toward carbapenem-resistant Gram-negative pathogens, with distinct profiles of associated factors across CRAB, CRE, and CRPA. These findings highlight the need for pathogen-specific infection prevention and antimicrobial stewardship strategies during healthcare system disruptions.

Evidence on the prognostic utility of biological markers in critically ill patients with COVID-19 across different geographic altitudes remains limited.

The aim of this study was to determine the prognostic value of inflammatory and hematological markers, particularly the neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV), for mortality risk in critically ill patients with COVID-19 receiving invasive mechanical ventilation and living at different geographic altitudes.

A multicenter retrospective cohort study was conducted using secondary data from a clinical database. A total of 362 critically ill patients with COVID-19 admitted to intensive care units (ICUs) between April 2020 and March 2022 were included. Patients were treated at three hospitals in Ecuador located at different altitudes: sea level (4 m above sea level [masl]), moderate altitude (2200 masl), and high altitude (2850 masl). Clinical, laboratory, and outcome data were obtained from electronic medical records.

The mean age was 54.44 years, and 71.27% of patients were male. Post hoc, altitude-stratified NLR and MPV thresholds were associated with increased odds of ICU mortality: at sea level, NLR ≥ 12.50 and MPV ≥ 8.80 fL; at moderate altitude, NLR ≥ 11.50 and MPV ≥ 9.80 fL; and at high altitude, NLR ≥ 16.30 and MPV ≥ 9.00 fL.

In mechanically ventilated patients with critical COVID-19, NLR and MPV values above post hoc, altitude-stratified cutoff points were associated with higher ICU mortality. However, because each altitude stratum corresponded to a different hospital and these thresholds were not ROC-derived or internally/externally validated, these findings should be interpreted as exploratory and hypothesis-generating.

Background: The differential diagnosis of respiratory distress syndrome (RDS) and congenital pneumonia (CP) in newborns remains a complex clinical challenge due to the similarity in their clinical manifestations and their potential to coexist. Objective: We aimed to determine differential diagnostic predictors of RDS and CP in newborns by using mathematical modeling and machine learning methods. Methods: A retrospective cohort study was conducted; de-identified medical records of 244 newborns (97 with RDS and 143 with CP) were collected to assess clinical, anamnestic, laboratory, and instrumental data by applying multiple regression analysis, ROC analysis, logistic regression models, and Random Forest. Results: Patients with CP presented with a more severe condition at admission (57.1% vs. 23.3%; p = 0.023), required mechanical ventilation (MV) more frequently (22.4% vs. 8.2%; p = 0.004), and were more often transferred to the intensive care unit (ICU) (77.3% vs. 55.7%; p = 0.001). They further had lower hemoglobin levels (151 ± 28 g/L vs. 164 ± 31 g/L; p = 0.001) and red blood cell counts (p = 0.021). Regression analysis demonstrated that the severity of the condition and the presence of cerebral ischemia were dependent on hemoglobin levels in the case of CP, while gestational age played a determining role in RDS. The machine learning models achieved an accuracy of 0.69 and an area under the curve (AUC) of 0.82 (Random Forest). The key predictors for differential diagnosis of RDS were low gestational age, hyperbilirubinemia, and congenital heart defects, while for CP, they were hemoglobin < 151 g/L, lymphocytes < 4.8 × 10³/μL, oxygen saturation < 90-91%, and cerebral ischemia. Conclusions: The use of mathematical modeling methods made it possible to identify prognostically significant predictors for the differential diagnosis of RDS and CP. The resulting models are best viewed as proof-of-concept tools for hypothesis generation and future research, as external validation is necessary before they can be considered for clinical use.

Severe asthma in children is challenging to manage due to high exacerbation rates and significant impacts on quality of life. Despite corticosteroids and bronchodilators, many patients remain symptomatic, highlighting the need for alternative treatments. Biologic therapies, such as omalizumab and mepolizumab, offer potential to reduce exacerbations and oral corticosteroid use. This study aimed to evaluate the efficacy of novel biologic therapies in managing severe pediatric asthma.

A systematic review was conducted following the PRISMA protocol and registered on PROSPERO (CRD42025634956). Studies published between January 2019 and December 2024 were included. Eligible articles were randomized clinical trials, cohort, and case-control studies involving biologic therapies, excluding those with adults, animals, or unrelated topics. Data extraction was performed in Microsoft Excel, and bias was assessed using the Newcastle-Ottawa tool and the Jadad scale.

Most trials analyzed omalizumab, with only one evaluating mepolizumab. These therapies significantly reduced asthma exacerbations, with effects sustained up to 6 years. Reductions in hospitalizations, PICU admissions, and ED visits were noted. Most studies used manufacturer-recommended doses, while some adjusted doses based on weight and/or IgE levels. Pulmonary function improved in seven studies (increased FEV1), while three showed no significant changes. A reduction in inhaled and oral corticosteroid use, FeNO, and eosinophil levels was observed, suggesting reduced airway inflammation. Most patients tolerated therapies well, with mild adverse events reported.

Biologic therapies, particularly omalizumab, show promising clinical benefits for managing severe pediatric asthma. Further studies are needed to assess their long-term safety and effectiveness.

Combined pulmonary fibrosis and emphysema (CPFE) is a distinct yet clinically underrecognised syndrome. Interstitial pneumonia is a common pulmonary manifestation of connective tissue diseases (CTDs), and some CTD-interstitial lung disease (CTD-ILD) patients have concurrent emphysema that is frequently overlooked clinically.

This study explored the clinical characteristics and factors associated with emphysema in CTD-ILD patients to guide clinical management.

This single-centre retrospective study included patients with CTD-related lung diseases from the ILD database of Xiangya Hospital. Patients were screened with standardised respiratory disease keywords and verified by chest HRCT. All eligible cases were stratified into CTD-ILD and CTD-CPFE groups based on emphysema presentation on re-assessed HRCT images.

Admission data, including demographics, comorbidities, inflammatory biomarkers, autoimmune antibodies, HRCT findings, pulmonary function test results and in-hospital treatment information, were collected for subsequent grouped analysis.

445 CTD-ILD patients were included, and 48 (10.8%) were CPFE. Patients with CPFE were predominantly male (68.8%), had a higher prevalence of a smoking history (68.8% vs 31.2%, p < 0.001), a lower body mass index (BMI) (20.4 vs 22.2 kg/m², P = 0.004), and a higher prevalence of prior tuberculosis (TB) (14.6% vs 4.3%, p = 0.009). Multivariable regression analysis showed that sex, BMI, smoking status, and history of TB were independently associated with CPFE. Male sex was associated with a markedly increased likelihood of CPFE (p = 0.003). TB was associated with increased likelihood, whereas higher BMI was associated with reduced likelihood (odds ratio: 33 and 0.57, respectively).

CTD-CPFE may represent a distinct subgroup within CPFE, with several characteristic features, including a relatively lower prevalence of smoking history. A low BMI and a history of TB were associated with the presence of CPFE, highlighting the potential importance of nutritional and immune status in patients with CTD-ILD.

Cystic Fibrosis (CF) and primary ciliary dyskinesia (PCD) are congenital disorders characterized by impaired mucociliary clearance, resulting in chronic airway infection, inflammation, and progressive lung damage. CF lung disease involves defective CFTR function throughout the entire airway epithelium, whereas PCD originates from dysfunction of motile respiratory cilia located predominantly in proximal airways. Diagnostic tools such as FEV₁ lack sensitivity to detect early peripheral lung damage. Lung clearance index (LCI), obtained via multiple breath washout (MBW), has emerged as a promising marker for early detection of lung abnormalities.

To compare LCI between age and FEV₁-matched people with (pw) CF and PCD (without highly effective CFTR modulator treatment), hypothesizing more abnormal LCI in CF due to more peripheral airway involvement. Secondary objectives included comparing phase III slope parameters (S_cond x VT, S_acin x VT) to explore ventilation inhomogeneity and localization of lung disease.

This retrospective cross-sectional study included pwCF and pwPCD aged 6-20 years with available MBW and spirometry data (2011-2024).

PwCF (n23, median age 14.4 y) had similar FEV₁ z-scores compared to 23 pwPCD (median age 14.4 y) (-0.1 vs. -1.1, p: 0.33). LCI values were more abnormal in the CF group compared to the PCD group (7.8 vs. 7.1; p: 0.04). FEF_25-75%pred and phase III slope parameters were not significantly different, though a trend toward higher S_cond x VT in CF was noted (0.08 vs. 0.06; p: 0.11).

Despite similar FEV₁ abnormalities, reflecting proximal airway impairment, pwCF exhibit greater peripheral airway involvement than pwPCD, as indicated by higher LCI values.

Nasal allergen provocation testing (NAPT) has been shown to be a safe and reproducible test in adults; however, pediatric data are limited. This study aims to investigate the clinical applications, feasibility, reproducibility and safety of NAPT in the pediatric population.

In this prospective study, 294 patients (4.16-14.25 years old, mean of 7.33 years), with symptoms and medical history of allergic rhinitis (AR) and IgE-mediated sensitization to Dermatophagoides pteronyssinus and Dermatophagoides farinae were recruited. Participants underwent NAPT with negative control and with increasing concentrations of crude Dermatophagoides farinae (50 µg/ml, 500 µg/ml, and 5000 µg/ml) at 15 min intervals. Pre- and post-test subjective symptom scores and objective active anterior rhinometry measurements were analyzed.

Among the 245 participants (83.3%) with a positive NAPT, the majority (n = 193, 78.8%) tested positive at 500 µg/ml or less. They (n = 226, 92.2%) were diagnosed based on an increase in total nasal symptoms score (TNSS) ≥ 5 points. The remaining 7.8% (n = 19) required objective measurements to fulfill the criteria for a positive result. Five participants were unable to fully comply with the instructions provided. There were no adverse events recorded during the study. The group which tested positive on NAPT recorded higher sIgE levels than that which tested negative. Furthermore, those with higher serum sIgE levels tested positive on NAPT at lower allergen concentrations. The baseline visual analog scale (VAS) was significantly higher in the group testing positive on NAPT at the lowest allergen concentration, compared with the other groups.

Our study demonstrates that NAPT is safe and feasible to be conducted on the pediatric population.

The clinical relevance of inherited thrombophilia-related polymorphisms in COVID-19 remains uncertain. This study investigated the distribution of Factor V Leiden (FVL) G1691A and MTHFR A1298C polymorphisms in patients with COVID-19 and associations with laboratory findings and short-term mortality.

This case-control study included 150 patients with PCR-confirmed COVID-19 and 300 controls. Genomic DNA was isolated from peripheral blood, and FVL G1691A and MTHFR A1298C polymorphisms were analyzed. Associations with d-dimer levels, hospitalization duration, and 30- and 90-day mortality were evaluated using multivariable linear and Cox regression analyses.

The FVL GG genotype was less frequent in patients than controls (77.3% vs. 87.0%, p = 0.009), whereas the MTHFR AA genotype was more frequent (76.7% vs. 61.3%, p = 0.001). Heterozygosity in both genes did not differ between groups (8.0% vs. 6.3%, p = 0.552). Patients with heterozygosity in both genes had higher d-dimer levels (median 435.0 vs. 201.0 ng/mL, p = 0.024) and longer hospitalization (median 7.5 vs. 5.0 days, p = 0.037). After adjustment, heterozygosity in both genes remained associated with higher log-transformed d-dimer levels (β = 0.758, 95% CI: 0.239-1.277; p = 0.005), as did MTHFR A1298C (β = 0.432, 95% CI: 0.007-0.856; p = 0.046). None of the polymorphisms was associated with 30- or 90-day mortality, while age independently predicted both outcomes.

Thrombophilia-related polymorphisms may influence d-dimer levels and hospitalization duration in COVID-19 but do not appear to affect short-term mortality.

Children with asthma may experience functional exercise limitations that are not fully reflected by resting lung function or conventional clinical assessments. Field-based exercise tests provide complementary information regarding functional capacity, and the International Classification of Functioning, Disability and Health (ICF) offers a biopsychosocial framework to contextualize activity limitations. However, the integration of objective exercise performance with ICF-aligned interpretation in pediatric asthma remains limited.

To interpret functional exercise capacity in children with asthma using Incremental Shuttle Walk Test (ISWT) performance through an exploratory operational framework conceptually aligned with ICF activity qualifiers and to examine its association with lung function, asthma control, quality of life, and demographic characteristics.

In this cross-sectional study, 39 children with asthma (mean age 8.6 ± 2.3 years) underwent spirometry, completed the Asthma Control Questionnaire (ACQ-6) and the Pediatric Asthma Quality of Life Questionnaire (PAQLQ), and performed the ISWT. Functional exercise capacity was expressed as a percentage of predicted ISWT distance and interpreted using an exploratory operational framework conceptually aligned with generic ICF activity qualifiers, generating two categories of activity limitation (mild/moderate and severe).

Resting lung function was relatively preserved (mean FEV₁ 82.0 ± 16.4% predicted), whereas functional exercise capacity was markedly reduced (mean ISWT 41.4 ± 18.7% predicted). Based on the exploratory ICF-aligned framework, 72% of participants were categorized as having severe activity limitation. Children with severe limitations walked significantly shorter distances than those with mild/moderate limitations (32.0 ± 11.5% vs. 65.3 ± 10.1% predicted; p < 0.001), with a very large effect size. Spirometric indices, asthma control, and quality of life scores did not differ between functional categories. ISWT performance was not correlated with lung function, asthma control, or quality of life and demonstrated a negative association with age.

Children with asthma may present substantial functional exercise limitations despite relatively preserved lung function and similar levels of asthma control and quality of life. The exploratory operational alignment of ISWT performance with generic ICF activity qualifiers may provide a clinically useful framework to support interpretation of activity limitations not captured by conventional assessments. However, this approach should be interpreted cautiously and requires future validation before broader clinical application.