The cohort comprised patients admitted to the Pain Department at Hengshui People’s Hospital in China between December 2020 and December 2023. Acute herpetic neuralgia was defined as pain occurring within 30 days after the appearance of a herpes zoster rash, with a Numerical Rating Scale score above 4. Eligible patients were at least 20 years old and had complete clinical and laboratory data from the index admission. The researchers excluded people with previous VTE, current anticoagulant or antiplatelet treatment, severe hepatic or renal dysfunction, known active malignancy, recent chemotherapy or radiotherapy, pregnancy or breastfeeding, and several unstable systemic conditions. Consequently, the findings describe a selected clinical population rather than all people with herpes zoster or neuralgia.

VTE outcomes were restricted to events occurring during the index hospitalization and confirmed by objective imaging. Deep vein thrombosis was diagnosed with compression or duplex ultrasonography, while pulmonary embolism was identified through computed tomography pulmonary angiography or, when that procedure was contraindicated, ventilation-perfusion scanning. Elevated D-dimer and clinical suspicion alone were not sufficient for diagnosis. The investigators collected demographic characteristics, comorbidities, laboratory measurements, pain scores and an admission thrombosis risk score from the first blood samples drawn after admission, before VTE diagnosis and before anticoagulant therapy. The thrombosis score was an institutional adaptation of the Caprini model, recorded as an aggregate from 0 to 8; individual Caprini items were not systematically documented.

Patients who developed VTE differed from those who did not in several baseline measures. Their median age was 75 years, compared with 65 years in the non-VTE group. Median fibrin degradation product concentration was 4.3 mg/L in the VTE group and 1.9 mg/L among those without VTE. Median Numerical Rating Scale scores were 8 and 7, respectively, and the median institutional thrombosis risk score was three in the VTE group and two in the non-VTE group. Elevated D-dimer, defined as a value above 0.5 mg/L fibrinogen-equivalent units, was present in 57.7% of patients with VTE and 13.3% of those without an event. These were observed group differences in a retrospective cohort, not evidence that any individual factor caused thrombosis.

To select candidate predictors, investigators used least absolute shrinkage and selection operator regression, commonly called LASSO, with 10-fold cross-validation to guide the regularization process. Ten variables were retained at the selected stage: sex, age, rheumatism and immunity, D-dimer, activated partial thromboplastin time, fibrinogen, fibrin degradation products, antithrombin III, Numerical Rating Scale score and thrombosis risk score. These variables were entered into multivariable logistic regression and refined through forward and backward stepwise selection based on the Akaike information criterion. Age correlated strongly with the institutional thrombosis risk score, at r = 0.627, because that assessment incorporated age; the age-related information was therefore largely captured by the score during variable selection. Fibrin degradation products had the strongest correlation with elevated D-dimer, at r = 0.582, and a weaker correlation with fibrinogen, at r = 0.357. Variance inflation factors for the four final predictors ranged from 1.018 to 1.534, indicating no meaningful multicollinearity within the model.

The final logistic regression associated three variables with higher adjusted odds of VTE and one with lower adjusted odds. Each 1 mg/L increase in fibrin degradation products was associated with an odds ratio of 1.48, with a 95% confidence interval of 1.282–1.737 and P less than 0.001. A one-point increase in the Numerical Rating Scale corresponded to an odds ratio of 1.584, with a 95% confidence interval of 1.05–2.538 and P = 0.039. Each additional point in the institutional thrombosis risk score was associated with an odds ratio of 2.05, with a 95% confidence interval of 1.455–2.947 and P less than 0.001. Fibrinogen was associated with lower odds, with an odds ratio of 0.477 per g/L, a 95% confidence interval of 0.275–0.798 and P = 0.006. These estimates describe conditional associations in the fitted model rather than interventions that would change a patient’s risk.

The inverse fibrinogen association requires particular caution. Fibrinogen was not significantly associated with VTE in the unadjusted analysis, with an odds ratio of 1.025 per g/L, a 95% confidence interval of 0.631–1.516 and P = 0.912. The inverse pattern emerged only after adjustment for fibrin degradation products and other correlated coagulation markers, which the authors considered more consistent with statistical suppression or negative confounding than with a directly protective biological effect. They also noted that fibrinogen is an acute-phase reactant and a substrate for fibrin formation, while citing inconsistent findings from previous studies about its relationship with VTE. Admission samples were obtained before VTE diagnosis and anticoagulant use, making treatment-related distortion unlikely. Likewise, severe pain might accompany reduced mobility and impaired venous flow, but bed-rest time and mobility status were not systematically recorded, so that proposed pathway could not be tested directly.

The four retained predictors were translated into a graphical nomogram that assigns points for fibrinogen, fibrin degradation products, Numerical Rating Scale score and the admission thrombosis risk score. Adding the assigned points yields an estimated probability of VTE during the index hospitalization. In the full cohort, the model’s apparent AUC was 0.853. Ten-fold cross-validation produced a C-index of 0.849, although its 95% confidence interval was wide, from 0.591 to 1.000, reflecting the limited number of events. Bootstrap validation with 1,000 repetitions yielded an optimism-corrected C-index of 0.834; the bootstrap distribution had a mean of 0.831 and a 95% confidence interval of 0.680–0.950. Because the model was developed on the full cohort of 327 patients rather than in a separate training sample, these results represent internal validation rather than evidence of performance in an independent population.

At the Youden-index cutoff of 0.094, the model identified 19 true positives and seven false negatives among the 26 patients with VTE, alongside 264 true negatives and 37 false positives among the 301 without VTE. Sensitivity was 0.731, with a 95% confidence interval of 0.522–0.884, and specificity was 0.877, with a 95% confidence interval of 0.835–0.912. Positive predictive value was 0.339, whereas negative predictive value was 0.974; overall accuracy was 0.865. The modest positive predictive value is consistent with the low base rate: most patients flagged as positive would not develop VTE. Calibration appeared close to the observed frequencies, with a Hosmer–Lemeshow chi-square value of 5.848 and P = 0.664, while decision-curve analysis indicated net benefit across most threshold probabilities.

Important limitations prevent the nomogram from being treated as a stand-alone diagnostic test. The retrospective, single-center design limits generalizability, and only 26 events occurred, creating substantial overfitting risk despite LASSO regularization and internal validation. Imaging was performed when clinically indicated rather than through universal screening, so asymptomatic events may have been missed and the reported incidence may be underestimated. Pharmacologic and mechanical prophylaxis was not systematically recorded, and residual confounding by prophylaxis therefore could not be excluded. Mobility data were unavailable, and the model could not be benchmarked against formally reconstructed Caprini, Padua or IMPROVE/IMPROVE-DD scores. The findings are therefore hypothesis-generating: larger multicenter prospective studies with standardized risk assessments, prophylaxis records and mobility data are needed before the model can be evaluated for routine clinical use.

Subject of Research: Development and internal validation of an in-hospital venous thromboembolism prediction model for adults with acute herpetic neuralgia

Article Title: Analysis of risk factors for venous thromboembolism in hospitalized patients with acute herpetic neuralgia and construction of a predictive nomogram model

Article References: Wang, C., Wang, G., Liu, B., Gao, Q., Du, C., & Li, L. (2026). Analysis of risk factors for venous thromboembolism in hospitalized patients with acute herpetic neuralgia and construction of a predictive nomogram model. Frontiers in Neurology, 17, Article 1877838. https://doi.org/10.3389/fneur.2026.1877838

Image Credits: AI Generated

DOI: 10.3389/fneur.2026.1877838

Keywords: acute herpetic neuralgia, venous thromboembolism, deep vein thrombosis, pulmonary embolism, prediction model, nomogram, fibrin degradation products, pain intensity, thrombosis risk score, clinical validation, Analysis, risk

Community-acquired pneumonia, or CAP, remains one of the most common and consequential infectious diseases worldwide. It is defined as pneumonia acquired outside of hospitals or long-term care facilities, and it presents clinicians with a persistent diagnostic dilemma: the symptoms, fever, cough, sputum production and breathlessness, overlap heavily with other respiratory conditions, and the causative pathogen is often never identified. Standard laboratory markers such as C-reactive protein (CRP), procalcitonin and the erythrocyte sedimentation rate are informative but imperfect, offering only coarse indications of inflammation rather than specific insight into the nature of the infection. The Chinese team set out to test whether NETs, as a direct readout of neutrophil activation by pathogens, could fill part of that gap.

The study enrolled 222 patients with community-acquired pneumonia admitted to a tertiary hospital in Lanzhou between January 2021 and December 2022. From each patient the researchers collected paired samples: peripheral blood serum and bronchoalveolar lavage fluid, or BALF, the liquid retrieved from the deep airways after it has been washed across the alveolar surfaces where the infection resides. As a baseline, they also gathered serum from 100 age- and gender-matched healthy volunteers. NETs levels in every specimen were quantified using a double-antibody sandwich enzyme-linked immunosorbent assay, an ELISA format in which capture antibodies immobilize NET-associated antigens from the sample and detection antibodies generate a measurable signal proportional to the amount of trap material present. Statistical analysis was performed with SPSS 25.0, with Pearson correlation used to relate NETs concentrations to routine laboratory indicators and receiver operating characteristic (ROC) curves used to evaluate diagnostic performance.

The first and most fundamental finding was that NETs are markedly elevated in pneumonia. Serum NETs levels in CAP patients were significantly higher than in healthy controls, and within the patients themselves, serum concentrations were substantially greater than the paired BALF concentrations, a difference that held at the stringent threshold of P < 0.001. This pattern is biologically interesting: it suggests that NETosis in pneumonia is not confined to the local lung environment but spills over into systemic circulation, where trap components or their degradation products become detectable in the blood. That spillover is precisely what makes serum NETs attractive as a clinical biomarker, because a blood draw is far simpler, faster and less invasive than bronchoscopy with lavage.

The researchers then stratified patients by whether a pathogen had been detected. Patients in whom a pathogen was identified showed elevated NETs levels in both serum and BALF compared with patients in whom no pathogen was found, with P values below 0.05. This supports the idea that NETs release is not merely a nonspecific consequence of lung inflammation but is actively driven by microbial invasion. When the analysis turned to the type of pathogen, a nuanced picture emerged. NETs levels did not differ significantly between patients with single bacterial infections and those with single viral infections, indicating that both major classes of respiratory pathogens provoke comparable NETotic responses as measured by this assay. However, the mixed-infection group, patients harboring both bacterial and viral pathogens simultaneously, exhibited significantly higher NETs levels in both serum and BALF than either single-infection group.

This last result may prove to be the study’s most clinically valuable contribution. Mixed infections in pneumonia are notoriously difficult to recognize at the bedside, yet they carry important therapeutic implications: a patient co-infected with influenza and Streptococcus pneumoniae, for example, may need both antiviral and antibacterial coverage, and missing one component can be fatal. If a simple serum measurement could flag the likelihood of a mixed infection, it could guide empiric therapy decisions, prompt more aggressive microbiological workup, and help steward antibiotics more rationally. The finding that NETs are amplified specifically in mixed infections, rather than merely in bacterial ones, suggests the biomarker reflects the total burden of pathogen-driven neutrophil activation rather than the identity of any single pathogen.

The correlation analysis reinforced the mechanistic coherence of the findings. Serum and BALF NETs levels were strongly correlated with the peripheral neutrophil count, which is expected since neutrophils are the source of the traps, and with fibrin degradation products (FDP), a marker of fibrin turnover. The link to FDP is notable because NETosis and coagulation are deeply intertwined: NETs provide scaffolding for thrombus formation, activate platelets, and interact with the coagulation cascade, while fibrinolytic products may in turn reflect the inflammatory meshwork that NETs help create. NETs levels were moderately correlated with monocyte count and only weakly correlated with CRP, suggesting that NETs capture a dimension of the immune response, granulocyte-driven and coagulation-linked, that conventional inflammatory markers only partially overlap.

For diagnostic performance, the ROC analysis delivered the headline numbers. Serum NETs yielded an area under the curve (AUC) of 0.8293 for distinguishing CAP patients from healthy controls, with an optimal cut-off value of 362.2. At that threshold, the assay achieved a sensitivity of 63.96 percent but a specificity of 98.00 percent. In practical terms, this profile describes a rule-in test: a positive result above the cut-off makes pneumonia highly likely, even though a negative result does not exclude it. High specificity is a prized property in emergency departments, where distinguishing true bacterial or viral pneumonia from heart failure, pulmonary embolism or other mimics can change management immediately. Used alongside clinical assessment and existing markers, a highly specific NETs measurement could add genuine discriminative value.

The authors conclude that community-acquired pneumonia induces significant NETs release, that pathogen invasion further upregulates NETs expression, and that this upregulation is prominently amplified in mixed-infection conditions. They position serum NETs as reliable biomarkers for the auxiliary diagnosis of CAP and for the identification of mixed infection, with favorable prospects for clinical application. The study was approved by the Ethics Committee of Gansu Provincial Center for Disease Control and Prevention under approval number 013 of 2019, and all participants provided informed consent. The work received support from the National Natural Science Foundation of China and several Gansu provincial funding programs, and it was conducted with technical assistance from the Virus Laboratory of the Gansu Provincial Center for Disease Control and Prevention and the Department of Clinical Laboratory Center of Lanzhou University Second Hospital.

As with any biomarker study, the path from these findings to routine clinical use will require further validation in independent and more diverse cohorts, standardization of the ELISA platform across laboratories, and clarification of how NETs measurements perform in patients with chronic inflammatory diseases, autoimmune conditions or other states of neutrophil activation that could confound specificity. The study was published as an open-access article under a Creative Commons Attribution 4.0 license, with the accepted manuscript released early for rapid access and citable under its permanent DOI. Even so, the conceptual advance is clear: a century-old view of neutrophils as simple phagocytes has given way to an appreciation of them as engineers of extracellular scaffolds, and those scaffolds, it turns out, leave measurable traces in a vial of blood that speak volumes about what is happening deep in the lungs. For a disease as common, costly and diagnostically slippery as community-acquired pneumonia, that is a signal worth pursuing.

Subject of Research: Neutrophil extracellular traps as diagnostic biomarkers for community-acquired pneumonia and mixed respiratory infections

Article Title: Diagnostic value of neutrophil extracellular traps in community-acquired pneumonia and their potential in identifying mixed infection

Article References: Zhang, H., Yang, X., Zhou, J., Wang, B., Wang, M., Zhang, X., & Li, J. (2026). Diagnostic value of neutrophil extracellular traps in community-acquired pneumonia and their potential in identifying mixed infection. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14390-4

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14390-4

Keywords: neutrophil extracellular traps, community-acquired pneumonia, biomarkers, mixed infection, ELISA, serum diagnostics, neutrophils, bronchoalveolar lavage fluid, ROC analysis, respiratory pathogens, C-reactive protein, fibrin degradation products