Determining the date of conception is important for estimating gestational age and monitoring whether the fetus and mother are on track in their development and pregnancy. Various methods based on ultrasound have been proposed for dating a pregnancy in high resource countries. However, such techniques may not be available in under-resourced countries. We develop a shared random parameter model for estimating the date of conception using longitudinal assessment of multiple maternal anthropometry and cross-sectional neonatal anthropometry. The methodology is evaluated with a training-test set paradigm as well as with simulations to examine the robustness of the method to model misspecification. We illustrate this new methodology with data from the NICHD Fetal Growth Studies.
Background
People with HIV and mycobacterial infections can develop immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy. Severe mycobacterial-IRIS has an overlapping clinical phenotype with hemophagocytic lymphohistiocytosis (HLH).
Objective
To evaluate the pathophysiologic similarities between mycobacterial-IRIS and HLH and identify clinical and immune predictors of mycobacterial-IRIS severity.
Methods
HLH-criteria were applied to a longitudinal cohort of 80-patients with HIV (CD4 < 100 cells/µL) and mycobacterial infections. Participants were subdivided into IRIS meeting HLH-criteria (HLH-IRIS), IRIS without HLH (IRIS), and those without IRIS (Non-IRIS). Clinical outcomes were evaluated by regression analyses. Soluble biomarkers and T-cell immune phenotypes were assessed at baseline and IRIS-equivalent timepoints.
Results
HLH-IRIS patients required corticosteroids more frequently (OR 21.5 [CI95% 5.6-114.8]) and for longer duration (21.2-weeks [CI95% 10.7-31.7]) than those not meeting HLH-criteria. Utilizing decision tree analyses, hemoglobin <9.2 g/dL was the best predictor of HLH-IRIS before antiretroviral treatment, whereas ferritin and immune markers (CXCL-9, sCD25) were most diagnostic for HLH at onset of IRIS. At the IRIS-timepoint, but not baseline, HLH-IRIS patients had lower regulatory and higher activated T-cells along with greater production of IFNγ-IL18 axis biomarkers compared to both IRIS and Non-IRIS groups. Principal component analysis corroborated the distinct clustering of HLH-IRIS patients.
Conclusion
Severe mycobacterial-IRIS and HLH have an overlapping pathogenesis involving IFNγ and unopposed T-cell activation causing severe inflammatory disease clinically distinguished by hyperferritinemia (hyperferritinemic IRIS or FIRIS). Hemoglobin, ferritin, CXCL-9, and sCD25 identify this high-risk population and may improve risk stratification and therapeutic strategies for mycobacterial-IRIS.
Objectives: Facial palsy is the most common manifestation of Lyme neuroborreliosis (LNB) in the United States. This study aimed to describe features of patients with early LNB presenting with facial palsy and to determine if corticosteroids in addition to antibiotic therapy was associated with unfavorable outcome. Methods: Retrospective analysis of participants enrolled in clinical studies investigating Lyme disease (N = 486) identified 44 patients who had facial palsy from LNB. The House-Brackmann scale was used to quantify the facial nerve dysfunction. Results: Most patients presented in the summer months. Erythema migrans, frequently associated with systemic symptoms, occurred in 29 patients. Thirteen patients presented with bilateral facial palsy, usually with sequential involvement. Fourteen patients had painful radiculopathy. Of the 38 patients treated with antibiotics before the resolution of the palsy who had complete follow-up, 24 received both antibiotics and corticosteroids. Of these 38 patients, 34 recovered completely, 3 had nearly complete recovery, and 1 had moderate dysfunction. There were no differences between the treatment groups in achieving complete resolution of the palsy at 12 months or in time to complete recovery. Interpretation: A history of rash compatible with erythema migrans or febrile illness in the weeks preceding the palsy are helpful clues pointing toward LNB and should be actively sought when evaluating patients with acute-onset peripheral facial palsy, particularly bilateral facial palsy. Treatment with antibiotic therapy is highly effective and most patients will fully recover facial nerve function. Adjunctive corticosteroid therapy appears to not affect the speed of recovery or overall outcome in this retrospective observational study.
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