Tranexamic acid in life-threatening military injury and the associated risk of infective complications.

BACKGROUND: Tranexamic acid (TXA) has been shown to reduce mortality from severe haemorrhage. Although recent data suggest that TXA has anti-inflammatory properties, few analyses have investigated the impact of TXA on infectious complications in injured patients. The aim was to examine the association between TXA administration and infection risk among injured military personnel. METHODS: Patients who received TXA were matched by Injury Severity Score with patients who did not receive TXA. Conditional logistic regression was used to examine risk factors associated with infections within 30 days. A Cox proportional analysis evaluated risk factors in a time-to-first-infection model. RESULTS: A total of 335 TXA recipients were matched with 626 patients who did not receive TXA. A greater proportion of TXA recipients had an infection compared with the comparator group (P < 0·001). Univariable analysis estimated an unadjusted odds ratio (OR) of 2·47 (95 per cent c.i. 1·81 to 3·36) for the association between TXA and infection risk; however, TXA administration was not significant in multivariable analysis (OR 1·27, 0·85 to 1·91). Blast injuries, intensive care unit (ICU) admission, and receipt of 10 units or more of blood within 24 h after injury were independently associated with infection risk. The Cox proportional model confirmed the association with ICU admission and blood transfusion. Traumatic amputations were also significantly associated with a reduced time to first infection. CONCLUSION: In life-threatening military injuries matched for injury severity, TXA recipients did not have a higher risk of having infections nor was the time to develop infections shorter than in non-recipients. Extent of blood loss, blast injuries, extremity amputations and ICU stay were associated with infection.

Combat trauma-associated invasive fungal wound infections: epidemiology and clinical classification.

The emergence of invasive fungal wound infections (IFIs) in combat casualties led to development of a combat trauma-specific IFI case definition and classification. Prospective data were collected from 1133 US military personnel injured in Afghanistan (June 2009-August 2011). The IFI rates ranged from 0·2% to 11·7% among ward and intensive care unit admissions, respectively (6·8% overall). Seventy-seven IFI cases were classified as proven/probable (n = 54) and possible/unclassifiable (n = 23) and compared in a case-case analysis. There was no difference in clinical characteristics between the proven/probable and possible/unclassifiable cases. Possible IFI cases had shorter time to diagnosis (P = 0·02) and initiation of antifungal therapy (P = 0·05) and fewer operative visits (P = 0·002) compared to proven/probable cases, but clinical outcomes were similar between the groups. Although the trauma-related IFI classification scheme did not provide prognostic information, it is an effective tool for clinical and epidemiological surveillance and research.

Determinants of incident chronic kidney disease and progression in a cohort of HIV-infected persons with unrestricted access to health care.

OBJECTIVES: As socioeconomic factors may impact the risk of chronic kidney disease (CKD), we evaluated the incidence and risk factors of incident CKD among an HIV-infected cohort with universal access to health care and minimal injecting drug use (IDU). METHODS: Incident CKD was defined as an estimated glomerular filteration rate (eGFR) <60 ml/min/1.73 m(2) for ≥ 90 days. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Rates were calculated per 1000 person-years (PY). Associations with outcomes were assessed using two separate Cox proportional hazard models, adjusting for baseline and time-updated covariates. RESULTS: Among 3360 participants [median age 29 years; 92% male; 44% African American (AA)] contributing 23,091 PY of follow-up, 116 developed incident CKD [5.0/1000 PY; 95% confidence interval (CI) 4.2-6.0/1000 PY]. The median first eGFR value was 97.0 mL/min/1.73 m(2) [interquartile range (IQR) 85.3-110.1 mL/min/1.73 m(2)]. Baseline factors associated with CKD included older age, lower CD4 count at HIV diagnosis [compared with CD4 count ≥ 500 cells/µL, hazard ratio (HR) 2.1 (95% CI 1.2-3.8) for CD4 count 350-499 cells/µL; HR 3.6 (95% CI 2.0-6.3) for CD4 count 201-349 cells/µL; HR 4.3 (95% CI 2.0-9.4) for CD4 count ≤ 200 cells/µL], and HIV diagnosis in the pre-highly active antiretroviral therapy (HAART) era. In the time-updated model, low nadir CD4 counts, diabetes, hepatitis B, hypertension and less HAART use were also associated with CKD. AA ethnicity was not associated with incident CKD in either model. CONCLUSIONS: The low incidence of CKD and the lack of association with ethnicity observed in this study may in part be attributable to unique features of our cohort such as younger age, early HIV diagnosis, minimal IDU, and unrestricted access to care. Lower baseline CD4 counts were significantly associated with incident CKD, suggesting early HIV diagnosis and timely introduction of HAART may reduce the burden of CKD.

Syphilis co-infection does not affect HIV disease progression.

HIV and syphilis are often seen as co-infections since they share a common mode of transmission. During episodes of syphilis, CD4 counts transiently decrease and HIV viral loads increase; however, the effect of syphilis co-infection on HIV disease progression (time to AIDS or death) is unclear. We analysed prospectively collected information on 2239 persons with estimated dates of HIV seroconversion (205 [9.2%] with confirmed syphilis and 66 [2.9%] with probable syphilis) in order to determine the effect of syphilis co-infection on HIV disease progression. In multivariate models censored at highly active antiretroviral therapy (HAART) initiation or last visit, adjusting for CD4 count, age, race, gender, and hepatitis B and C status, syphilis (confirmed + probable) was not associated with increased hazard of AIDS or death (hazard ratio 0.99, 95% CI 0.73-1.33). Treating HAART as a time-varying covariate or limiting the analysis to only confirmed syphilis cases did not significantly alter the results. Despite transient changes in CD4 counts and viral loads, syphilis does not appear to affect HIV disease progression.

Potential role of nitric oxide in the pathophysiology of experimental bacterial meningitis in rats.

We have investigated the possible role of nitric oxide (NO) in the pathophysiology of bacterial meningitis (BM) by using the rat model of experimental BM. The nitrite concentration in cerebrospinal fluid (CSF) was used as a measure of NO production in vivo since NO rapidly degrades to nitrite and nitrate. Rats were inoculated intracisternally with live bacteria (5 x 10(6) CFU of Haemophilus influenzae type b strain DL42 or Rd-/b+/O2), with bacterial endotoxin (20 ng of DL42 lipooligosaccharide [LOS] or 200 ng of Escherichia coli lipopolysaccharide), or with a saline control vehicle. CSF samples were collected preinoculation and at the time of maximal alteration in blood-brain barrier permeability (BBBP). CSF [nitrite] was quantified by measuring A550 after addition of the Greiss reagent and comparison to a standard curve of sodium nitrite. Rats inoculated with either DL42, Rd-/b+/O2, LOS, or lipopolysaccharide demonstrated a significantly elevated mean peak CSF [nitrite] (8.34, 15.62, 10.75, and 10.44 mM, respectively) versus the concentration prior to treatment and/or those in saline-treated animals (5.29 and 5.33 mM, respectively; P < 0.05 for each comparison). We then determined if there was a correlation between CSF [nitrite] and percent BBBP (%BBBP) at various time points postinoculation with Rd-/b+/O2. %BBBP was defined as the concentration of systemically administered 125I-labeled bovine serum albumin in the CSF divided by the level of 125I-labeled bovine serum albumin in serum multiplied by 100. The mean %BBBP increased in tandem with the mean CSF [nitrite] (R = 0.84, P = 0.018), which peaked at 18 h in the absence of a change in the serum [nitrite]. Systemic administration of the NO synthase inhibitor N-nitro-L-arginine methyl ester demonstrated a significant reduction of mean CSF nitrite production (0.95 versus 6.0 mM in controls; P = 0.02) when administered intravenously to animals which had been inoculated intracisternally with 20 ng of LOS. Suppression of mean leukocyte pleocytosis (3,117 versus 11,590 leukocytes per mm3 in control LOS-challenged rats; P = 0.03) and mean alterations of BBBP (2.11 versus 6.49% in control LOS-challenged rats; P = 0.009) was observed concomitantly with decreased CSF [nitrite]. These results support the hypothesis that NO contributes to increased %BBBP in experimental BM.