Excess mortality, length of stay, and costs associated with serious hemorrhage among trauma patients: findings from the National Trauma Data Bank

Trauma is a serious injury or shock to the body from violence or crash and is an important and growing global health risk. Using 2000 to 2004 data from a comprehensive trauma registry, we estimated the prevalence of serious blunt and penetrating trauma-related hemorrhage among patients admitted to U.S. trauma centers along with excess in-hospital mortality, length of hospital stay, and inpatient costs. There were 65,750 patients with blunt trauma and 12,992 patients with penetrating trauma included in our analyses. Of patients sustaining blunt trauma, 7.6 per cent had serious hemorrhage; 18.8 per cent of patients sustaining penetrating trauma had serious hemorrhage. In-hospital mortality rates were significantly (P < 0.05) higher for patients with serious hemorrhage than for patients without (24.9 per cent versus 8.4 per cent for blunt; 23.4 per cent versus 4.2 per cent for penetrating). Patients with serious hemorrhage had adjusted mean excess lengths of stay of 0.4 days for blunt trauma and 2.7 days for penetrating trauma (P < 0.05); adjusted excess costs were $296 per day for patients sustaining blunt trauma and $637 per day for patients sustaining penetrating trauma (P < 0.05). In both blunt and penetrating trauma cases, serious hemorrhage is significantly associated with excess mortality, longer hospital stays, and higher costs.     

Chondroprotective role of the osmotically sensitive ion channel transient receptor potential vanilloid 4: Age‐ and sex‐dependent progression of osteoarthritis in Trpv4‐deficient mice

Objective

Mechanical loading significantly influences the physiology and pathology of articular cartilage, although the mechanisms of mechanical signal transduction are not fully understood. Transient receptor potential vanilloid 4 (TRPV4) is a Ca⁺⁺‐permeable ion channel that is highly expressed by articular chondrocytes and can be gated by osmotic and mechanical stimuli. The goal of this study was to determine the role of Trpv4 in the structure of the mouse knee joint and to determine whether Trpv4^–/– mice exhibit altered Ca⁺⁺ signaling in response to osmotic challenge.

Methods

Knee joints of Trpv4^–/– mice were examined histologically and by microfocal computed tomography for osteoarthritic changes and bone structure at ages 4, 6, 9, and 12 months. Fluorescence imaging was used to quantify chondrocytic Ca⁺⁺ signaling within intact femoral cartilage in response to osmotic stimuli.

Results

Deletion of Trpv4 resulted in severe osteoarthritic changes, including cartilage fibrillation, eburnation, and loss of proteoglycans, that were dependent on age and male sex. Subchondral bone volume and calcified meniscal volume were greatly increased, again in male mice. Chondrocytes from Trpv4^+/+ mice demonstrated significant Ca⁺⁺ responses to hypo‐osmotic stress but not to hyperosmotic stress. The response to hypo‐osmotic stress or to the TRPV4 agonist 4α‐phorbol 12,13‐didecanoate was eliminated in Trpv4^–/– mice.

Conclusion

Deletion of Trpv4 leads to a lack of osmotically induced Ca⁺⁺ signaling in articular chondrocytes, accompanied by progressive, sex‐dependent increases in bone density and osteoarthritic joint degeneration. These findings suggest a critical role for TRPV4‐mediated Ca⁺⁺ signaling in the maintenance of joint health and normal skeletal structure.

     

Amygdala response to faces parallels social behavior in Williams syndrome

Individuals with Williams syndrome (WS), a genetically determined disorder, show relatively strong face-processing abilities despite poor visuospatial skills and depressed intellectual function. Interestingly, beginning early in childhood they also show an unusually high level of interest in face-to-face social interaction. We employed functional magnetic resonance imaging (fMRI) to investigate physiological responses in face-sensitive brain regions, including ventral occipito-temporal cortex and the amygdala, in this unique genetic disorder. Participants included 17 individuals with WS, 17 age- and gender-matched healthy adults (chronological age-matched controls, CA) and 17 typically developing 8- to 9-year-old children (developmental age controls, DA). While engaged in a face discrimination task, WS participants failed to recruit the amygdala, unlike both CA and DA controls. WS fMRI responses in ventral occipito-temporal cortex, however, were comparable to those of DA controls. Given the integral role of the amygdala in social behavior, the failure of WS participants to recruit this region during face processing may be a neural correlate of the abnormally high sociability that characterizes this disorder.     

Hepatitis C Prevalence in Patients With Hepatocellular Carcinoma Without Cirrhosis

BackgroundHepatocellular carcinoma (HCC) occurring in “noncirrhotic” hepatitis C virus (HCV)-infected patients has been reported; but the exact prevalence or incidence has not been described before.MethodsWe conducted a systematic review of literature: Ovid was used to search the literature from January 1, 1990, to September 1, 2008. Articles containing “HCC” keywords (hepatocellular carcinoma, hepatoma, liver cancer) were combined with the word “cirrhosis” or “fibrosis” and with “absence” keywords [noncirrhotic, absence, without]. Two hundred articles were selected and screened according to predesigned exclusion and inclusion criteria.ResultsNineteen articles met the inclusion criteria. The estimated prevalence of noncirrhotic HCC ranged from 6.7% to 50.1%. The pooled prevalence estimates for HCV in noncirrhotic HCC ranged from 0% and 68.4% according to the geographic location. Reports from Japan had the highest estimated pooled prevalence of HCV (55.01%) followed by Italy (29.95%).ConclusionsHCV can occur in patients with HCC without cirrhosis, but the true incidence and prevalence are very difficult to ascertain. Further studies are needed to define this group of patients.     

Systemic activation of the transient receptor potential vanilloid subtype 4 channel causes endothelial failure and circulatory collapse: Part 2

The transient receptor potential (TRP) vanilloid subtype 4 (V4) is a nonselective cation channel that exhibits polymodal activation and is expressed in the endothelium, where it contributes to intracellular Ca2+ homeostasis and regulation of cell volume. The purpose of the present study was to evaluate the systemic cardiovascular effects of GSK1016790A, a novel TRPV4 activator, and to examine its mechanism of action. In three species (mouse, rat, and dog), the i.v. administration of GSK1016790A induced a dose-dependent reduction in blood pressure, followed by profound circulatory collapse. In contrast, GSK1016790A had no acute cardiovascular effects in the TRPV4-/- null mouse. Hemodynamic analyses in the dog and rat demonstrate a profound reduction in cardiac output. However, GSK1016790A had no effect on rate or contractility in the isolated, buffer-perfused rat heart, and it produced potent endothelial-dependent relaxation of rodent-isolated vascular ring segments that were abolished by nitric-oxide synthase (NOS) inhibition (N-nitro-L-arginine methyl ester; L-NAME), ruthenium red, and endothelial NOS (eNOS) gene deletion. However, the in vivo circulatory collapse was not altered by NOS inhibition (L-NAME) or eNOS gene deletion but was associated with (concentration and time appropriate) profound vascular leakage and tissue hemorrhage in the lung, intestine, and kidney. TRPV4 immunoreactivity was localized in the endothelium and epithelium in the affected organs. GSK1016790A potently induced rapid electrophysiological and morphological changes (retraction/condensation) in cultured endothelial cells. In summary, inappropriate activation of TRPV4 produces acute circulatory collapse associated with endothelial activation/injury and failure of the pulmonary microvascular permeability barrier. It will be important to determine the role of TRPV4 in disorders associated with edema and microvascular congestion.     

Temporal trends in maternal mortality in Canada II: estimates based on hospitalization data

ObjectivesWorld Health Organization reports based on Canadian Vital Statistics data suggest a recent increase in maternal mortality mrates in Canada. Since Vital Statistics data typically provide inaccurate estimates of maternal mortality, we examined temporal trends in Canada using hospitalization data.MethodsWe identified in-hospital deaths among women aged 15 to 54 years from the Canadian Institute for Health Information’s hospitalization database from 1996–1997 to 2007–2008. Maternal deaths during delivery were identified, and other in-hospital deaths were linked with prior pregnancy/delivery hospitalization records. Maternal mortality rates, 95% confidence intervals, and risk ratios (RRs) were estimated.ResultsThe maternal mortality rate in Canada was 9.2 per 100 000 deliveries (95% CI 7.6 to 11.2) in 1996 to 1999 and 9.0 per 100 000 deliveries (95% CI 7.4 to 10.9) in 2005 to 2007 (P for trend = 0.22). Older maternal age (RR 9.9 and 3.1 for ≥ 45 years and 40 to 44 years vs. 20 to 24 years), delivery by Caesarean section (RR 4.5 vs. vaginal delivery), and early gestation delivery (RR 20.1 and 5.9 for 20 to 27 weeks and 28 to 36 weeks vs. ≥ 37 weeks) were associated with higher maternal mortality. Cardiovascular diseases (rate 4.7 per 100 000 deliveries, 95% CI 3.9 to 5.5) were the most common diagnoses associated with maternal death. The rate of late maternal death (from 43 to 365 days after delivery) was 5.4 per 100 000 deliveries.ConclusionThere was no increase in maternal mortality in Canada from 1996 to 2007. Increases observed in Canadian Vital Statistics data likely reflect improvements in the ascertainment of maternal death. Hospitalization data can serve as a timely and comprehensive source for monitoring trends in maternal mortality in Canada.     

Argatroban anticoagulation in intensive care patients: effects of heart failure and multiple organ system failure

We retrospectively evaluated argatroban dosing patterns, clinical outcomes, and the effects of heart failure and multiple organ system failure on dosing requirements in 65 adult, intensive care patients administered argatroban anticoagulation for clinically suspected heparin-induced thrombocytopenia (n=56) or history of heparin-induced thrombocytopenia (n=9). Argatroban was initiated then titrated to achieve target activated partial thromboplastin times 1.5 to 3 times normal control (ie, 42-84 seconds). Overall, argatroban was initiated at 1.14+/-0.62 microg/kg/min (mean+/-SD) and administered for 11.4+/-9.5 days, with comparable dosing patterns between patients with suspected, versus previous, heparin-induced thrombocytopenia. Sixty-four (98.5%) patients achieved target activated partial thromboplastin times, typically following no or one dose adjustment. Therapeutic doses were lower in patients with, versus without, heart failure (0.58+/-0.28 vs 0.97+/-0.6 microg/kg/min, P= .042) and decreased as the number of failed organ systems increased from 1 to 2 to =3 (1.10+/-0.67 vs 0.87+/-0.47 vs 0.58+/-0.47 microg/kg/min, P= .008). From argatroban initiation until patient discharge or death, 11 (16.9%) patients (3 off argatroban) developed thromboembolic complications; 14 (21.5%) died (11 off argatroban, 7 from multiple organ system failure); and 1 (1.5%) required amputation. Nine patients (13.8%) experienced bleeding, none fatal. This experience suggests that argatroban administered at approximately 1 micro/kg/min provides adequate levels of anticoagulation in many intensive care unit patients with suspected or previous heparin-induced thrombocytopenia. Reduced doses are needed when heart failure or multiple organ system failure is present.     

Tolerability and Safety of a Novel Ketogenic Ester,Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults

Nutritional ketosis is a state of mildly elevated blood ketone concentrations resulting from dietary changes (e.g., fasting or reduced carbohydrate intake) or exogenous ketone consumption. In this study, we determined the tolerability and safety of a novel exogenous ketone diester, bis-hexanoyl-(R)-1,3-butanediol (BH-BD), in a 28-day, randomized, double-blind, placebo-controlled, parallel trial ({"type":"clinical-trial","attrs":{"text":"NCT04707989","term_id":"NCT04707989"}}NCT04707989). Healthy adults (n = 59, mean (SD), age: 42.8 (13.4) y, body mass index: 27.8 (3.9) kg/m²) were randomized to consume a beverage containing 12.5 g (Days 0–7) and 25 g (Days 7–28) of BH-BD or a taste-matched placebo daily with breakfast. Tolerability, stimulation, and sedation were assessed daily by standardized questionnaires, and blood and urine samples were collected at Days 0, 7, 14, and 28 for safety assessment. There were no differences in at-home composite systemic and gastrointestinal tolerability scores between BH-BD and placebo at any time in the study, or in acute tolerability measured 1-h post-consumption in-clinic. Weekly at-home composite tolerability scores did not change when BH-BD servings were doubled. At-home scores for stimulation and sedation did not differ between groups. BH-BD significantly increased blood ketone concentrations 1-h post-consumption. No clinically meaningful changes in safety measures including vital signs and clinical laboratory measurements were detected within or between groups. These results support the overall tolerability and safety of consumption of up to 25 g/day BH-BD.