Isolated abnormal diffusing capacity for carbon monoxide (iso↓DLco) is associated with increased respiratory symptom burden in people with HIV infection.

OBJECTIVES: An isolated reduction in the diffusing capacity for carbon monoxide (DLco; iso↓DLco) is one of the most common pulmonary function test (PFT) abnormalities in people living with HIV (PWH), but its clinical implications are incompletely understood. In this study, we explored whether iso↓DLco in PWH is associated with a greater respiratory symptom burden. STUDY DESIGN: Cross-sectional analysis. METHODS: We used ATS/ERS compliant PFTs from PWH with normal spirometry (post-bronchodilator FEV1/FVC ≥0.7; FEV1, FVC ≥80% predicted) from the I AM OLD cohort in San Francisco, CA and Seattle, WA, grouped by DLco categorized as normal (DLco ≥lower limit of normal, LLN), mild iso↓DLco (LLN >DLco >60% predicted), and moderate-severe iso↓DLco (DLco ≤60% predicted). We performed multivariable analyses to test for associations between DLco and validated symptom-severity and quality of life questionnaires, including the modified Medical Research Council dyspnea scale (mMRC), the COPD Assessment Test (CAT), and St. George's Respiratory Questionnaire (SGRQ), as well as between DLco and individual CAT symptoms. RESULTS: Mild iso↓DLco was associated only with a significantly higher SGRQ score. Moderate-severe iso↓DLco was associated with significantly higher odds of mMRC ≥2 and significantly higher CAT and SGRQ scores. PWH with moderate-severe iso↓DLco had increased odds of breathlessness, decreased activity, lower confidence leaving home, and less energy. CONCLUSIONS: Iso↓DLco is associated with worse respiratory symptom scores, and this association becomes stronger with worsening DLco, suggesting that impaired gas exchange alone has a significant negative impact on the quality of life in PWH. Additional studies are ongoing to understand the etiology of this finding and design appropriate interventions.

Platelet Transfusion and Outcomes After Massive Transfusion Protocol Activation for Major Trauma: A Retrospective Cohort Study.

BACKGROUND: Incorporation of massive transfusion protocols (MTPs) into acute major trauma care has reduced hemorrhagic mortality, but the threshold and timing of platelet transfusion in MTP are controversial. This study aimed to describe early (first 4 hours) platelet transfusion practice in a setting where platelet counts are available within 15 minutes and the effect of early platelet deployment on in-hospital mortality. Our hypothesis in this work was that platelet transfusion in resuscitation of severe trauma can be guided by rapid turnaround platelet counts without excess mortality. METHODS: We examined MTP activations for all admissions from October 2016 to September 2018 to a Level 1 regional trauma center with a full trauma team activation. We characterized platelet transfusion practice by demographics, injury severity, and admission vital signs (as shock index: heart rate/systolic blood pressure) and laboratory results. A multivariable model assessed association between early platelet transfusion and mortality at 4 hours, 24 hours, and overall in-hospital, with P <.001. RESULTS: Of the 11,474 new trauma patients admitted over the study period, 469 (4.0%) were massively transfused (defined as ≥10 units of red blood cells [RBCs] in 24 hours, ≥5 units of RBC in 6 hour, ≥3 units of RBC in 1 hour, or ≥4 units of total products in 30 minutes). 250 patients (53.0%) received platelets in the first 4 hours, and most early platelet transfusions occurred in the first hour after admission (175, 70.0%). Platelet recipients had higher injury severity scores (mean ± standard deviation [SD], 35 ± 16 vs 28 ± 14), lower admission platelet counts (189 ± 80 × 10 9 /L vs 234 ± 80 × 10 9 /L; P < .001), higher admission shock index (heart rate/systolic blood pressure; 1.15 ± 0.46 vs 0.98 ± 0.36; P < .001), and received more units of red cells in the first 4 hours (8.7 ± 7.7 vs 3.3 ± 1.6 units), 24 hours (9 ± 9 vs 3 ± 2 units), and in-hospital (9 ± 8 vs 3 ± 2 units) than nonrecipients (all P < .001). We saw no difference in 4-hour (8% vs 7.8%; P = .4), 24-hour (16.4% vs 10.5%; P = .06), or in-hospital mortality (30.4% vs 23.7%; P = .1) between platelet recipients and nonrecipients. After adjustment for age, injury severity, head injury, and admission physiology/laboratory results, early platelet transfusion was not associated with 4-hour, 24-hour, or in-hospital mortality. CONCLUSIONS: In an advanced trauma care setting where platelet counts are available within 15 minutes, approximately half of massively transfused patients received early platelet transfusion. Early platelet transfusion guided by protocol-based clinical judgment and rapid-turnaround platelet counts was not associated with increased mortality.

Markers of inflammation and immune activation are associated with lung function in a multi-center cohort of persons with HIV.

OBJECTIVES: Studies have shown that people with HIV (PWH) may be at increased risk for chronic lung diseases and lung function abnormalities, which may be associated with immune activation. We tested the association of a panel of 12 immune activation and inflammation biomarkers with spirometry and single-breath diffusing capacity for carbon monoxide (DLco). DESIGN: Cross-sectional, observational study. METHODS: Participants were enrolled from the Inflammation, Aging, Microbes and Obstructive Lung Disease cohort of PWH at two US sites. Biomarkers were examined and standardized spirometry and DLco testing were performed. We tested associations between each biomarker and lung function, examined individually and in combination, using multi-variable linear and logistic regression. RESULTS: Among 199 participants, median forced expiratory volume in 1 s (FEV1) was normal (90% predicted) and median DLco was abnormal (69% predicted). The most common lung function abnormality (57%) was a normal FEV1 to forced vital capacity ratio with an abnormal DLco of 80% or less predicted (iso↓DLco). Two markers (IL-6, high-sensitivity C-reactive protein) were associated with FEV1% predicted, whereas eight markers (soluble CD14, soluble CD163, inducible protein-10, soluble CD27, IL-6, soluble tumor necrosis factor receptors 1 and 2, D-dimer) were associated with DLco% predicted. Compared with those participants with normal spirometry and DLco, five markers (soluble CD14, soluble CD163, interferon gamma inducible protein-10, soluble tumor necrosis factor receptors 1 and 2) were associated with iso↓DLco. CONCLUSION: Among PWH, different markers of immune activation and inflammation are associated with FEV1% predicted than with DLco% predicted and with an iso↓DLco, representing possible unique pathways of chronic lung disease. Identifying plausible drivers of these inflammatory pathways may clarify mechanisms underlying impaired lung function in HIV infection and may identify therapeutic avenues.

Early changes in cerebral autoregulation among youth hospitalized after sports-related traumatic brain injury.

OBJECTIVE: To examine early cerebral haemodynamic changes among youth hospitalized with sports-related traumatic brain injury (TBI). STUDY DESIGN: Youth 0-18 years admitted to a level one trauma centre with sports-related TBI were enrolled. Daily measures included clinical symptoms and Glasgow Coma Scale (GCS) score. Using Transcranial Doppler (TCD) ultrasonography and tilt testing, we measured middle cerebral artery flow velocity (Vmca) and cerebral autoregulation index (ARI). RESULTS: Six previously healthy males age 14 (IQR 12-16) years with headache and abnormal head CT were admitted with median admission GCS 15. Six patients underwent 12 TCD examinations between hospital days 0-9. Low Vmca occurred in 3/6 patients and on the side of TBI, whereas high Vmca occurred in 2/6 patients. Five patients had at least one measurement of impaired and five patients had absent cerebral autoregulation of at least one hemisphere; all these five patients had GCS 15 and headache during TCD examinations. Three patients were discharged with absent cerebral autoregulation. Five (83%) patients were discharged to home and one patient was discharged to a rehabilitation facility. CONCLUSION: Headache, abnormal Vmca and impaired cerebral autoregulation occur after sports-related TBI, despite normal GCS. Headache may signal underlying neurovascular abnormality in sports-related TBI.

Intensive care treatments associated with favorable discharge outcomes in Argentine children with severe traumatic brain injury: For the South American Guideline Adherence Group.

OBJECTIVE: Little is known about the critical care management of children with traumatic brain injury (TBI) in low middle income countries. We aimed to identify indicators of intensive care unit (ICU) treatments associated with favorable outcomes in Argentine children with severe TBI. METHODS: We conducted a secondary analysis of data from patients previously enrolled in a prospective seven center study of children with severe TBI who were admitted to an ICU in one of the seven study centers. Severe TBI was defined by head AIS ≥ 3, head CT with traumatic lesion, and admission GCS < 9. Seven indicators of best practice TBI care were examined. The primary outcome was discharge Pediatric Cerebral Performance Category Scale [PCPC] and Pediatric Overall Performance category Scale [POPC]. We also examined variation in ICU care and in-patient mortality. RESULTS: Of the 117 children, 67% were male and 7.5 (4.3) years on average, 92% had isolated TBI. Hypotension (54%) was more common than hypoxia (28%) and clinical or radiographic signs of high intracranial pressure (ICP) were observed in 92%. Yet, ICP monitoring occurred in 60% and hyperosmolar therapy was used in only 36%. Adherence to indicators of best TBI practice ranged from 55.6% to 83.7% across the seven centers and adherence was associated with favorable discharge PCPC (aRR 0.98; 95% CI [0.96, 0.99]), and POPC (aRR 0.98; 95% CI [0.96, 0.99]). Compared to patients whose adherence rates were below 65%, patients whose adherence rates were higher between 75%-100% had better discharge PCPC (aRR 0.28; 95% CI [0.10, 0.83]) and POPC (aRR 0.32; 95% CI [0.15, 0.73]. Two indicators were associated with favorable discharge PCPC: Avoidance of hypoxia (aRR 0.46; 95% CI [0.23, 0.93]), and Nutrition started in 72 hours (aRR 0.45; 95% CI [0.21, 0.99]). Avoiding hypoxia was also associated with favorable discharge POPC (aRR 0.47; 95% CI [0.22, 0.99]). CONCLUSION: There is variation in Argentine ICU practice in the care of children with severe TBI. Second insults are common and hyperosmolar therapy use is uncommon. Adherence to best practice TBI care by avoiding hypoxia and providing timely nutrition were associated with significantly favorable discharge outcomes. Implementing strategies that prevent hypoxia and facilitate early nutrition in the ICUs are urgently needed to improve pediatric TBI outcomes.