Effect of Prolonged Methylprednisolone Therapy in Unresolving Acute Respiratory Distress Syndrome: A Randomized Controlled Trial

Context.— No pharmacological therapeutic protocol has been found effective in modifying the clinical course of acute respiratory distress syndrome (ARDS) and mortality remains greater than 50%. Objective.— To determine the effects of prolonged methylprednisolone therapy on lung function and mortality in patients with unresolving ARDS. Design.— Randomized, double-blind, placebo-controlled trial. Setting.— Medical intensive care units of 4 medical centers. Participants.— Twenty-four patients with severe ARDS who had failed to improve lung injury score (LIS) by the seventh day of respiratory failure. Interventions.— Sixteen patients received methylprednisolone and 8 received placebo. Methylprednisolone dose was initially 2 mg/kg per day and the duration of treatment was 32 days. Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment. Main Outcome Measures.— Primary outcome measures were improvement in lung function and mortality. Secondary outcome measures were improvement in multiple organ dysfunction syndrome (MODS) and development of nosocomial infections. Results.— Physiological characteristics at the onset of ARDS were similar in both groups. At study entry (day 9 [SD, 3] of ARDS), the 2 groups had similar LIS, ratios of PaO₂ to fraction of inspired oxygen (FIO₂), and MODS scores. Changes observed by study day 10 for methylprednisolone vs placebo were as follows: reduced LIS (mean [SEM], 1.7 [0.1] vs 3.0 [0.2]; P<.001); improved ratio of PaO₂ to FIO₂ (mean [SEM], 262 [19] vs 148 [35]; P<.001); decreased MODS score (mean [SEM], 0.7 [0.2] vs 1.8 [0.3]; P<.001); and successful extubation (7 vs 0; P=.05). For the treatment group vs the placebo group, mortality associated with the intensive care unit was 0 (0%) of 16 vs 5 (62%) of 8 (P=.002) and hospital-associated mortality was 2 (12%) of 16 vs 5 (62%) of 8 (P=.03). The rate of infections per day of treatment was similar in both groups, and pneumonia was frequently detected in the absence of fever. Conclusions.— In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.      

Influence of switch region length on immunoglobulin class switch recombination

The class and effector functions of antibodies are modulated through the process of Ig heavy chain class switch recombination (CSR). CSR occurs between switch (S) regions that lie upstream of the various Ig heavy chain constant region exons. Molecular analyses of S-region functions have been hampered by their large size and repetitive nature. To test potential relationships between S-region size and efficiency of CSR, we generated normal B lymphocytes in which the 12-kb S region flanking the Cgamma1 exons (Sgamma1) was replaced with synthetic or endogenous S regions of various lengths. Replacement of Sgamma1 with 1- and 2-kb synthetic sequences representing the Sgamma1 core repeats or a 4-kb portion of the core endogenous Sgamma1 region supported CSR frequencies that directly correlated with S-region length. These findings indicate that S-region size is an important factor in determining endogenous CSR efficiency. Moreover, these results also will allow the development of a systematic system to test the function of various S-region motifs by replacing endogenous S regions with synthetic S regions controlled for size effects.     

Commensal microbiota alter the abundance and TCR responsiveness of splenic naïve CD4+ T lymphocytes

The epidemiologic risk of certain systemic immunologic diseases is affected by commensal or environmental microbiota, but the cellular basis of the "hygiene hypothesis" is poorly understood. In this study, we demonstrate that composition of the commensal microbiota affects the functional state of the peripheral na?ve (CD62L(hi)CD44(lo)) T lymphocyte populations. Restricted flora (RF) mice (stably colonized with excess nonpathogenic Clostridium sp., and changes in other bacterial and fungal taxa) were distinguished after the neonatal period by a progressive deficiency in absolute numbers of na?ve CD4+ and CD8+ T lymphocytes. SPF and RF mice had comparable levels of memory CD4+ and CD8+ T cells. This phenotype was attributable to the altered levels of certain commensals and their products, since germ-free mice had normal absolute numbers of splenic CD4+ and CD8+ T cells and their respective na?ve and memory subsets. The na?ve CD4+ T cell subset was functionally distinguished in RF mice versus SPF mice by TCR hyperresponsiveness, pro-inflammatory cytokine production, and increased activation-induced cell death. Biochemically, these traits were associated with higher basal phosphorylation of the TCR signaling proteins ZAP-70, Lck, and LAT. These findings indicate that enteric microbial products, through unknown cellular circuitry, influence steps in CD4 T cell differentiation moderating basal TCR signaling and immune responsiveness.     

Molecular tests can allow confirmation of invasive meningococcal disease when isolates yield atypical maltose, glucose or gamma-glutamyl peptidase test results

Analysis of atypical meningococci from invasive disease that either (i) did not produce acid from maltose and glucose or (ii) were gamma-glutamyl peptidase test negative for porA and porB DNA variable region (VR) type, multilocus sequence type, and for presence of capsule transport gene ctrA, conclusively demonstrated that these are Neisseria meningitidis.     

Hydrolyzed olive vegetation water in mice has anti-inflammatory activity

Fruit and vegetable simple and polyphenols are potent antioxidants. One of the most effective in terms of free radical scavenging is 3,4-dihydroxyphenyl ethanol or hydroxytyrosol (HT), a simple phenol found predominantly in Olea europea, or the olive plant. HT is most abundant in the aqueous fraction of olive pulp with trace amounts in the olive oil fraction and in the leaves. For these experiments, we evaluated the anti-inflammatory activity of olive vegetation water (OVW), which we showed previously to have potent antioxidant activity. Because some simple phenols and polyphenols with antioxidant activity have shown varying anti-inflammatory activities, we tested OVW and HT for their ability to inhibit the production of tumor necrosis factor-alpha (TNF-alpha), a pivotal cytokine in inflammation. In lipopolysaccharide (LPS)-treated BALB/c mice, a model system of inflammation, OVW at a dose of 125 mg/mouse (500 mg/kg) reduced serum TNF-alpha levels by 95%. In the human monocyte cell line, THP-1, OVW reduced LPS-induced TNF-alpha production by 50% at a concentration of 0.5 g/L (equivalent to approximately 0.03 g/L simple and polyphenols). OVW had no toxic effects in vitro or in vivo. When OVW was combined with glucosamine, a component of proteoglycans and glycoproteins that was shown to decrease inducible nitric oxide synthase production in cultured macrophage cells, the 2 compounds acted synergistically to reduce serum TNF-alpha levels in LPS-treated mice. These findings suggest that a combination of OVW and glucosamine may be an effective therapy for a variety of inflammatory processes, including rheumatoid and osteoarthritis.     

Infra-inguinal revascularization surgical site infections: Australasian benchmark

BACKGROUND: Infra-inguinal revascularization surgery remains one of the most commonly performed major vascular procedures in contemporary practice. Surgical site infections (SSI) are a common cause of morbidity in this patient cohort and generate high rates of limb loss and mortality when vascular graft involvement occurs. An overall reduction in North American SSI has been attributed to the establishment of national benchmarks. A comparable Australasian benchmark does not exist. The purpose of the present study was to assess the methods used by Australasian vascular units to determine SSI rates and to instigate the development of an acceptable benchmark. METHODS: A structured questionnaire pertaining to SSI after infra-inguinal revascularization surgery was sent to 26 Australasian vascular units. Data requested included the number and type of lower extremity revascularization procedures performed. Units were also asked to report the methods employed for defining and detecting wound infections and to document their SSI rate. The incidence of SSI causation by methicillin-resistant Staphylococcus aureus (MRSA) was also sought. RESULTS: The total number of revascularizations performed annually varied from 28 to 179 between units. The SSI rates ranged from 0 to 38%. The incidence of MRSA involvement varied from <1% to 56%. The SSI surveillance methodology varied considerably between units. CONCLUSIONS: The present study confirms the significant incidence of SSI after infra-inguinal revascularization surgery in contemporary vascular practice. Standardized definitions and surveillance protocols are required to facilitate inter- and intrahospital comparisons. A possible benchmark infection rate may be 10-20%.     

Coming home from jail: the social and health consequences of community reentry for women, male adolescents, and their families and communities

Each year, more than 10 million people enter US jails, most returning home within a few weeks. Because jails concentrate people with infectious and chronic diseases, substance abuse, and mental health problems, and reentry policies often exacerbate these problems, the experiences of people leaving jail may contribute to health inequities in the low-income communities to which they return.Our study of the experiences in the year after release of 491 adolescent males and 476 adult women returning home from New York City jails shows that both populations have low employment rates and incomes and high rearrest rates. Few received services in jail. However, overall drug use and illegal activity declined significantly in the year after release. Postrelease employment and health insurance were associated with lower rearrest rates and drug use. Public policies on employment, drug treatment, housing, and health care often blocked successful reentry into society from jail, suggesting the need for new policies that support successful reentry into society.     

Endovascular repair of abdominal aortic aneurysm reduces intraoperative cortisol and perioperative morbidity

BACKGROUND: The release of catabolic stress hormones because of surgical trauma leads to a breakdown of fats, proteins, and carbohydrate stores and interference with immune function. This can delay wound healing and may increase the risk of systemic inflammatory response syndrome (SIRS)/sepsis and postoperative complications. Minimally invasive surgery can attenuate this response. Our purpose was (1) to compare neuroendocrine responses in patients undergoing open abdominal aneurysm repair with those in patients undergoing endovascular aneurysm repair (EVAR), (2) to compare the incidence of SIRS/sepsis and all complications in these two groups, and (3) to look at the relationship between procedure type, neuroendocrine response, and incidence of SIRS/sepsis and complications. METHODS: Forty-six patients who underwent open repair and 19 who underwent EVAR were studied. A baseline (T1) 24-hour urine save was undertaken in the week before admission, and a second 24-hour save (T2) commenced at anesthetic induction to measure cortisol and catecholamines. The incidences of SIRS/sepsis and complications were recorded. RESULTS: Significant ( P 相似文献   

The value of electronic health records in solo or small group practices

We conducted case studies of fourteen solo or small-group primary care practices using electronic health record (EHR) software from two vendors. Initial EHR costs averaged $44,000 per full-time-equivalent (FTE) provider, and ongoing costs averaged $8,500 per provider per year. The average practice paid for its EHR costs in 2.5 years and profited handsomely after that; however, some practices could not cover costs quickly, most providers spent more time at work initially, and some practices experienced substantial financial risks. Policies should be designed to provide incentives and support services to help practices improve the quality of their care by using EHRs.