Objective: Following a 9-year 60% decline, chlamydia positivity increased 46% from 1997 through 2004 among young sexually active women screened in Region X family planning clinics. The objective of ...this analysis was to systematically examine the influences of risk factors, changing laboratory test methods, and interclinic variability on chlamydia positivity during this period. Study Design: We analyzed data from 520,512 chlamydia tests from women aged 15 to 24 years screened in 125 family planning clinics. Multivariate logistic regression modeling was used to adjust the annual risk of chlamydia for the demographic, clinical, and sexual risk behavior characteristics associated with infection and for the increasing use of more sensitive laboratory test methods. A generalized linear mixed model was used to adjust for interclinic variability. Results: We found a significant 5% annual increase in the risk of chlamydia even after adjusting for risk factors including laboratory test characteristics (odds ratio 1.05, 95% confidence interval: 1.04, 1.06). Variability among the clinics where screening occurred did not account for the increase. Conclusions: Based on a review of all available data, we concluded that there was a true increase in chlamydia positivity over the 8-year period.
The 23rd Acute Disease Quality Initiative (ADQI-23) consensus conference proposed a framework to integrate biomarkers into the staging of acute kidney injury (AKI). It is unknown whether tissue ...inhibitor of metalloproteinases 2 (TIMP-2) and insulinlike growth factor binding protein 7 (IGFBP7) could be used for staging.
To test whether higher levels of urinary TIMP-2 × IGFBP7 are associated with lower survival among patients with the same functional stage of AKI.
This cohort study was performed using data from the Protocolized Care for Early Septic Shock (ProCESS) trial, which enrolled critically ill patients with septic shock who presented at academic and community emergency departments and intensive care units in the US from March 2008 to May 2013. Patients with end-stage kidney disease, a reference serum creatinine level of 4 mg/dL or greater (to convert to μmol/L, multiply by 76.25), or missing data on serum creatinine levels or urinary levels of TIMP-2 × IGFBP7 were excluded. Data were analyzed from October 2020 to October 2021.
The presence of AKI, assessed using Kidney Disease: Improving Global Outcomes criteria within 24 hours after enrollment and the highest AKI stage as well as urinary TIMP-2 × IGFBP7 level at 6 hours after enrollment. A previously reported high-specificity cutoff level for TIMP-2 × IGFBP7 of 2.0 (ng/mL)2/1000 was used to categorize patients (including those without functional criteria of AKI) according to the new staging system proposed by the ADQI-23 as biomarker negative (urinary TIMP-2 × IGFBP7 level ≤2.0 ng/mL2/1000) or biomarker positive (TIMP-2 × IGFBP7 >2.0 ng/mL2/1000).
Survival (assessed using Kaplan-Meier plots and the log-rank test) and mortality (assessed using relative risk RR 30 days after enrollment).
The analysis included 999 patients with a median age of 61 years (IQR, 50-73 years); 554 (55.5%) were male. Biomarker-positive patients had lower survival and higher mortality at 30 days in the groups with AKI stage 1 (RR, 2.20; 95% CI, 1.02-4.72), stage 2 (RR, 1.53; 95% CI, 1.04-2.27), and stage 3 (RR, 1.61; 95% CI, 1.00-2.60). The associations were specific to patients with AKI. No difference in 30-day survival was found between biomarker-positive and biomarker-negative patients in the absence of functional criteria for AKI (RR, 1.16; 95% CI, 0.45-3.01).
The findings suggest that assessment of the cell-cycle arrest biomarkers TIMP-2 and IGFBP7 may augment AKI staging for patients with functional criteria for AKI.
Asthma is a chronic airway inflammatory disease that is associated with a large influx of inflammatory cells. Several chemokines and chemokine receptors play critical roles in the development of ...allergic airway inflammation.
Because polarized human T(H)2 cells express a functional CXCR3 chemokine receptor, we evaluated the effects of a selective CXCR3 inhibitor in a mouse model of allergic airway disease.
Ovalbumin-specific CD8(+) T effector cells were generated from OT-1 mice in the presence of interleukin 2. The activity of a CXCR3 inhibitor was examined in vitro by monitoring Ca(2+) influx after receptor ligation. In vivo, the activity was assessed in sensitized and challenged mice by monitoring airway function, inflammatory parameters, including cellular infiltrates and cytokines in the bronchoalveolar lavage fluid.
Approximately 40% of CD8(+) T effector cells expressed the CXCR3 receptor. In vitro, CXCR3 antagonism reduced Ca(2+) influx after receptor engagement. In contrast, the CXCR3 antagonist had little to no effect on airway function or inflammatory parameters despite adequate exposure levels.
CXCR3 antagonism did not prevent allergen-induced airway hyperresponsiveness or airway inflammation in a mouse allergy model despite having activity in in vitro functional assays.
Background
Interleukin-1 receptor antagonists can reduce mortality in septic shock patients with hepatobiliary dysfunction and disseminated intravascular coagulation (HBD + DIC), an organ failure ...pattern with inflammatory features consistent with macrophage activation. Identification of clinical phenotypes in sepsis may allow for improved care. We aim to describe the occurrence of HBD + DIC in a contemporary cohort of patients with sepsis and determine the association of this phenotype with known macrophage activation syndrome (MAS) biomarkers and mortality. We performed a retrospective nested case–control study in adult septic shock patients with concurrent HBD + DIC and an equal number of age-matched controls, with comparative analyses of all-cause mortality and circulating biomarkers between the groups. Multiple logistic regression explored the effect of HBD + DIC on mortality and the discriminatory power of the measured biomarkers for HBD + DIC and mortality.
Results
Six percent of septic shock patients (
n
= 82/1341) had HBD + DIC, which was an independent risk factor for 90-day mortality (OR = 3.1, 95% CI 1.4–7.5,
p
= 0.008). Relative to sepsis controls, the HBD + DIC cohort had increased levels of 21 of the 26 biomarkers related to macrophage activation (
p
< 0.05). This panel was predictive of both HBD + DIC (sensitivity = 82%, specificity = 84%) and mortality (sensitivity = 92%, specificity = 90%).
Conclusion
The HBD + DIC phenotype identified patients with high mortality and a molecular signature resembling that of MAS. These observations suggest trials of MAS-directed therapies are warranted.
To assess the short-term safety and efficacy of treating subfoveal choroidal neovascularization (CNV) with external beam radiation delivered in 5 × 4 Gy fractions among patients having age-related ...macular degeneration (AMD).
A multicenter prospective randomized controlled pilot study.
Eighty-eight patients were enrolled through 10 sites and were randomized to radiotherapy (20 Gy delivered in 5 daily fractions of 4 Gy each; 6 MV N = 41) or no radiotherapy (sham radiotherapy N = 22 or observation N = 25). Eligibility criteria included visual acuity of at least 20/320 and subfoveal CNV not amenable to treatment. Randomization was stratified by lesion type (new or recurrent CNV) and blood (<50% or ≥50% of the lesion N = 13). The primary outcome measure was loss of ≥3 lines of visual acuity. Secondary outcome measures were angiographic response and side effects.
At baseline, patient and ocular characteristics were similar between treatment groups. At six months, 9 radiated eyes (26%) and 17 eyes not radiated (49%) lost ≥3 lines of visual acuity (
P = .04; stratified χ
2 test). At 12 months, 13 radiated eyes (42%) and 9 observed eyes (49%) lost ≥3 visual acuity lines (
P = .60). The radiated group demonstrated smaller lesions and less fibrosis than the nonradiated group (
P = .05 and .004, respectively) at 12 months. Radiation-induced complications were not observed except for one radiated eye with numerous cotton wool spots and possible radiation retinopathy.
External beam radiation at 5 × 4 Gy may have a modest and short-lived (six month) benefit in preserving visual acuity.
To report initial mortality findings from the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy vs enucleation for treatment of choroidal melanoma.
...Patients were evaluated for eligibility at 43 participating clinical centers in the United States and Canada. Eligible consenting patients were assigned randomly at the time of enrollment to enucleation or 125I brachytherapy. Patients were examined at specified intervals after enrollment for data collection purposes. Findings presented herein are based on data received by September 30, 2000. Data for each patient were analyzed with the treatment group to which the patient was assigned randomly at the time of enrollment.
During the 11(1/2)-year accrual period, 1317 patients enrolled; 660 were assigned randomly to enucleation and 657 to 125I brachytherapy. Only 2 patients in the enucleation arm were found to have been misdiagnosed when histopathology was reviewed centrally. All but 17 patients (1.3%) received the assigned treatment. Adherence to the brachytherapy protocol was excellent, with 91% of patients treated per protocol. Based on time since enrollment, 1072 patients (81%) had been followed for mortality for 5 years and 416 (32%) for 10 years. A total of 364 patients had died: 188 (28%) of 660 patients in the enucleation arm and 176 (27%) of 657 patients in the brachytherapy arm. The unadjusted estimated 5-year survival rates were 81% and 82%, respectively; there was no clinically or statistically significant difference in survival rates overall (P =.48, log-rank test). The adjusted estimated risk ratio for 125I brachytherapy vs enucleation was 0.99 (95% confidence interval CI, 0.80-1.22). Five-year rates of death with histopathologically confirmed melanoma metastasis were 11% and 9% following enucleation and brachytherapy, respectively; after adjustment, the estimated risk ratio was 0.91 (95% CI, 0.66-1.24).
Mortality rates following 125I brachytherapy did not differ from mortality rates following enucleation for up to 12 years after treatment of patients with choroidal melanoma who enrolled in this COMS trial. The power of the study was sufficient to indicate that neither treatment is likely to increase or decrease mortality rates by as much as 25% relative to the other.
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