Association between early glycemic control and improvements in markers of coagulation and fibrinolysis in patients with septic shock–induced stress hyperglycemia

Purpose

The purpose of this study is to evaluate the coagulation and inflammatory profiles in septic shock patients with baseline hyperglycemia under glycemic control.

Methods

Prospective, observational study conducted in an intensive care unit of a university hospital, including 41 septic shock nondiabetic patients with hyperglycemia (n = 21) or normoglycemia (n = 20) profiles at baseline. Hyperglycemic patients received a glucose control protocol (target glycemia, < 150 mg/dL). Metabolic, inflammatory, and coagulation markers were measured at baseline and after 24 hours.

Results

Median glycemic values between groups were different at baseline but not after 24 hours. Baseline coagulation profile was similar in both groups with elevated levels of coagulation markers, reduced factor VII, protein C, and antithrombin activities and fibrinolysis impairment. Normoglycemic patients had unchanged coagulation markers after 24 hours. After treatment, previously hyperglycemic patients exhibited increased plasminogen concentrations (P = .03) and reduced levels of plasminogen activator inhibitor 1 (P = .01) and tissue plasminogen activator (P = .03) as compared with baseline. They also had higher factor VII (P = .03), protein C (P = .04), and antithrombin (P = .04) activities than normoglycemic patients. Inflammatory markers were elevated in both groups and improved after 24 hours, independently of the glycemic profile.

Conclusions

Glycemic control during septic shock is associated with improvements in coagulation and fibrinolysis parameters compared with baseline and normoglycemic patients.     

Implementation of a multifaceted sepsis education program in an emerging country setting: clinical outcomes and cost-effectiveness in a long-term follow-up study

Purpose

To evaluate whether a multifaceted, centrally coordinated quality improvement program in a network of hospitals can increase compliance with the resuscitation bundle and improve clinical and economic outcomes in an emerging country setting.

Methods

This was a pre- and post-intervention study in ten private hospitals (1,650 beds) in Brazil (from May 2010 to January 2012), enrolling 2,120 patients with severe sepsis or septic shock. The program used a multifaceted approach: screening strategies, multidisciplinary educational sessions, case management, and continuous performance assessment. The network administration and an external consultant provided performance feedback and benchmarking within the network. The primary outcome was compliance with the resuscitation bundle. The secondary outcomes were hospital mortality, hospital and ICU length of stay, quality-adjusted life year (QALY) gain, and cost-effectiveness.

Results

The proportion of patients who received all the required items for the resuscitation bundle improved from 13 % [95 % confidence interval (CI) 8–18 %] at baseline to 62 % (95 % CI 54–69 %) in the last trimester (p < 0.001). Hospital mortality decreased from 55 % (95 % CI 48–62 %) to 26 % (95 % CI 19–32 %, p < 0.001). Full compliance with the resuscitation bundle was associated with lower risk of hospital mortality (propensity weighted corrected risk ratio 0.74; 95 % CI 0.56–0.94, p = 0.02). There was a reduction in the total cost per patient from 29.3 (95 % CI 23.9–35.4) to 17.5 (95 % CI 14.3–21.1) thousand US dollars from baseline to the last 3 months (mean difference ?11,815; 95 % CI ?18,604 to ?5,338). The mean QALY increased from 2.63 (95 % CI 2.15–3.14) to 4.06 (95 % CI 3.58–4.57). For each QALY, the full compliance saves US$5,383.

Conclusions

A multifaceted approach to severe sepsis and septic shock patients in an emerging country setting led to high compliance with the resuscitation bundle. The intervention was cost-effective and associated with a reduction in mortality.     

Electrocortical Analysis of Patients with Intercostobrachial Pain Treated with TENS after Breast Cancer Surgery

[Purpose] Among the physical therapeutic procedures to decrease pain, there is transcutaneous electrical neural stimulation (TENS). There is no consensus about its efficacy for oncological patients, especially for post-mastectomy pain and eletrocortical changes in somatosensory areas. The aim of this study was to analyze acute electrocortical changes after TENS treatment of patients with intercostobrachial post mastectomy pain. [Subjects] Eighteen patients were divided into acupuncture (A) and burst (B) group. [Methods] In this pre and post-intervention study each group was measured for EEG analysis in absulte power in alpha band (8–14 Hz). Outcomes variables were the alpha waveband in the sensorymotor cortex and pain pre-and-post TENS intervention. Data were analyzed using ANOVA to compare times (rest, 10 and 15 min), group and electrodes. Pain was analyzed using percentual pain evaluation (PPE) in both groups. [Results] Outcomes indicate main effects of time and electrodes because of slow (8–10 Hz) and fast alpha (10–12 Hz) wavebands decreased. PPE reduced 88.4% in A and 66.3% in G. [Conclusion] TENS promoted electrical modification in the parietal region and a decrease in pain. Future studies should investigate other wave must be proposed for other bands and use different methods of EEG analysis to elucidate the actual mechanisms behind the efficacy of TENS treatment.Key words: Transcutaneous electric nerve stimulation, Mastectomy, Electroencephalography     

Comparative Analysis Electroencephalographic of Alpha,Beta and Gamma Bands of a Healthy Individual and One with Hemiparesis

[Purpose] The study analyzed the electroencephalographic (EEG) data of the central cortical areas, during execution of the motor gestures of feeding, activation of the system of mirror neurons, and imagery between a right hemiparetic volunteer (RHV) and a healthy volunteer (HV). [Subjects and Methods] The volunteers’ EEG data were recorded with their eyes open for 4 minutes while they performed five experimental tasks. [Results] The alpha band, absolute power value of HV was lower than that of RHV. In the beta band, during the practice condition, there was an increase in the magnitude of the absolute power value of HV at T3, possibly because T3 is representative of secondary motor areas that work with cortical neurons related to planning and organizing sequence of movements performed by the hands. The gamma band is related to the state of preparation for movement and memory. The results of this study indicate that there was increased activation of the gamma frequency band of HV. [Conclusion] The findings of this study have revealed the changes in pattern characteristics of each band which may be associated with the brain injury of the hemiparetic patient.Key words: Electroencephalography, Hemiparetic, Rehabilitation     

Doxycycline use in patients with lymphangioleiomyomatosis: biomarkers and pulmonary function response ,

OBJECTIVE:

To assess blockade of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the variation in FEV₁, in patients with lymphangioleiomyomatosis (LAM) treated with doxycycline (a known MMP inhibitor) for 12 months.

METHODS:

An open-label, single-arm, interventional clinical trial in which LAM patients received doxycycline (100 mg/day) for 12 months. Patients underwent full pulmonary function testing, a six-minute walk test, and quality of life assessment, as well as blood and urine sampling for quantification of MMP-2, MMP-9, and VEGF-D levels-at baseline, as well as at 6 and 12 months after the initiation of doxycycline.

RESULTS:

Thirty-one LAM patients received doxycycline for 12 months. Although there was effective blockade of urinary MMP-9 and serum MMP-2 after treatment, there were no significant differences between pre and post-doxycycline serum levels of MMP-9 and VEGF-D. On the basis of their response to doxycycline (as determined by the variation in FEV₁), the patients were divided into two groups: the doxycycline-responder (doxy-R) group (n = 13); and the doxycycline-nonresponder (doxy-NR) group (n = 18). The patients with mild spirometric abnormalities responded better to doxycycline. The most common side effects were mild epigastric pain, nausea, and diarrhea.

CONCLUSIONS:

In patients with LAM, doxycycline treatment results in effective MMP blockade, as well as in improved lung function and quality of life in those with less severe disease. However, these benefits do not seem to be related to the MMP blockade, raising the hypothesis that there is a different mechanism of action.     

NAL1 allele from a rice landrace greatly increases yield in modern indica cultivars

Increasing crop production is essential for securing the future food supply in developing countries in Asia and Africa as economies and populations grow. However, although the Green Revolution led to increased grain production in the 1960s, no major advances have been made in increasing yield potential in rice since then. In this study, we identified a gene, SPIKELET NUMBER (SPIKE), from a tropical japonica rice landrace that enhances the grain productivity of indica cultivars through pleiotropic effects on plant architecture. Map-based cloning revealed that SPIKE was identical to NARROW LEAF1 (NAL1), which has been reported to control vein pattern in leaf. Phenotypic analyses of a near-isogenic line of a popular indica cultivar, IR64, and overexpressor lines revealed increases in spikelet number, leaf size, root system, and the number of vascular bundles, indicating the enhancement of source size and translocation capacity as well as sink size. The near-isogenic line achieved 13–36% yield increase without any negative effect on grain appearance. Expression analysis revealed that the gene was expressed in all cell types: panicles, leaves, roots, and culms supporting the pleiotropic effects on plant architecture. Furthermore, SPIKE increased grain yield by 18% in the recently released indica cultivar IRRI146, and increased spikelet number in the genetic background of other popular indica cultivars. The use of SPIKE in rice breeding could contribute to food security in indica-growing regions such as South and Southeast Asia.The world’s population is expected to surpass 9 billion in 2050 (http://esa.un.org/unpd/ppp/index.htm). Most of this increase will occur in the developing countries of Asia and Africa. By 2035, a 26% increase in rice production will be essential to feed the rising population (1, 2). Rice (Oryza sativa L.) is a staple food of more than 3 billion people, mainly in Asia. Predominantly, indica cultivars are grown in southern China, Southeast Asia, and South Asia, occupying approximately 70% of the rice-producing area in the world, whereas japonica cultivars are grown mainly in East Asia (3, 4). Because of urbanization and industrialization, an increase in the yield of indica cultivars is a pressing need in Southeast and South Asia (5). Additionally, good grain quality (influencing market value) and high yield are essential for the adoption of new cultivars in local areas (6).The grain yield of rice is determined by spikelet number per panicle, panicle number per plant, grain weight, and spikelet fertility. Although many quantitative trait loci (QTLs) for yield components have been identified (www.gramene.org), few have so far been isolated. To date, at least nine genes or loci for yield-related traits in rice have been isolated from natural variation: Gn1a and APO1 for number of grains (7–9); GS3, GW2, and qSW5 for grain size (10–12); DEP1 and WFP for panicle architecture (13, 14); SCM2 for strong culm (15); and Ghd7 for late heading and number of grains (16). APO1, SCM2, and DEP1 increased grain yield in a japonica genetic background in field experiments (9, 13, 15). However, no novel cloned gene has been reported to increase grain yield in indica cultivars (17). Here, we identified a gene in a tropical japonica landrace and used the allele to increase the grain yield of modern indica cultivars at the crop level through a breeding concept developed by International Rice Research Institute (IRRI) breeders more than 20 y ago.In 1989, a breeding program for New Plant Type (NPT) rice was launched at IRRI to increase the yields of modern indica cultivars by using genetic material from tropical japonica landraces (18). Several Indonesian tropical japonica landraces—which are characterized by large panicles, large leaves, a vigorous root system, thick stems, and few unproductive tillers—have been used in international breeding programs. However, despite these features, the NPT cultivars yield less than modern indica cultivars, mainly because of low grain fertility and low panicle number (19, 20). To genetically dissect and elicit the valuable traits of NPT cultivars, we backcrossed the NPT cultivars including YP9 (IR68522-10-2-2) against modern indica cultivar IR64 to develop introgression lines (ILs) (Fig. S1). BC₃-derived ILs, which had favorable yield-related traits and few undesirable traits, were selected by field observation (21). Using the ILs, we identified 21 QTLs for yield components such as total spikelet number per panicle (TSN), grain weight, and panicle number. Among the QTLs, qTSN4, for high TSN, was commonly detected on the long arm of chromosome 4 in five NPT lines derived from different tropical japonica cultivars (22). Additionally, a near-isogenic line (NIL) for qTSN4 from YP9, derived from tropical japonica landrace Daringan with an IR64 genetic background, had more spikelets per panicle and more branches than IR64.In this study, we isolated the gene for qTSN4 through map-based cloning to facilitate its use in breeding. The phenotypic effects of the gene were validated in transgenic plants and by expression analysis. To confirm the effect on practical grain yield in the field, we evaluated yield and related traits by using NILs with genetic backgrounds of popular indica cultivars.     

Influence of the CCR-5/MIP-1 α Axis in the Pathogenesis of Rocio Virus Encephalitis in a Mouse Model

Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5−/− mice, while MIP-1 α−/− mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection.