Presentation of Case. Dr. Andrew S. Hoekzema (Medicine): An 83-year-old woman was admitted to this hospital in the winter because of nausea, vomiting, diarrhea, and confusion. One week before admission, rhinorrhea, sore throat, and nonproductive cough developed. The patient felt feverish but did…
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Τετάρτη 16 Μαΐου 2018
Case 15-2018: An 83-Year-Old Woman with Nausea, Vomiting, and Confusion
Injuries Among Recreational Football Players: Results of a Prospective Cohort Study
Objectives: To establish the incidence and patterns of football injuries and associated consequences in daily life and labor loss, among public employees. Design: Prospective cohort study. Setting: Football tournament between public employees in Turkey. Participants: A total of 1821 recreational players from 78 teams. Main Outcome Measures: Injury rates (injuries per 1000 hours of football exposure) during tournament by age group, as well as prevalence, severity, and injury types were recorded. The data regarding the occurrence (eg, location, type, circumstances) and consequences (eg, absenteeism, medical treatment, labor loss) of injuries were collected. Results: Of the 1821 football players registered for participation, 57% (n = 1038) were included in the study with the returned questionnaire forms. In total, 257 matches were played with a total exposure time of 5654 hours. A total of 218 injuries were recorded in 192 players (10.5%), resulting in a mean of 0.85 time-loss injuries per match (38.6 per 1000 hours). Severe injuries constituted 42.6% of all injuries, and 28.9% of all injuries caused the participants to be absent at least 1 day for the next working day. The total labor loss was 1196 days for all injuries. The rate of missing subsequent working day was significantly less for muscle injuries (Phttps://ift.tt/2IsETS3
Effect of E-Bike Versus Bike Commuting on Cardiorespiratory Fitness in Overweight Adults: A 4-Week Randomized Pilot Study
Objective: To assess if active commuting with an electrically assisted bicycle (e-bike) during a 4-week period can induce increases in cardiorespiratory fitness measured as peak oxygen uptake (V[Combining Dot Above]O2peak) in untrained, overweight individuals, and if these changes are comparable with those induced by a conventional bicycle. Design: Four-week randomized pilot study. Setting: Controlled laboratory. Participants: Thirty-two volunteers (28 men) participated. Seventeen {median age 37 years [interquartile range (IQR) 34, 45], median body mass index [BMI] 29 kg/m2 [IQR 27, 31]} were randomized to the E-Bike group and 15 [median age 43 years (IQR 38, 45), median BMI 28 kg/m2 (IQR 26, 29)] to the Bike group. Interventions: Participants in both groups were instructed to use the bicycle allocated to them (e-bike or conventional bicycle) for an active commute to work in the Basel (Switzerland) area at a self-chosen speed on at least 3 days per week during the 4-week intervention period. Main Outcome Measures: V[Combining Dot Above]O2peak was assessed before and after the intervention in an all-out exercise test on a bicycle ergometer. Results: V[Combining Dot Above]O2peak increased by an average of 3.6 mL/(kg·min) [SD 3.6 mL/(kg·min)] in the E-Bike group and by 2.2 mL/(kg·min) [SD 3.5 mL/(kg·min)] in the Bike group, with an adjusted difference between the 2 groups of 1.4 mL/(kg·min) [95% confidence interval, −1.4-4.1; P = 0.327]. Conclusions: E-bikes may have the potential to improve cardiorespiratory fitness similar to conventional bicycles despite the available power assist, as they enable higher biking speeds and greater elevation gain.https://ift.tt/2IJzysP
Near Point of Convergence and Gait Deficits in Adolescents After Sport-Related Concussion
Objective: To prospectively examine gait characteristics of participants acutely after concussion with and without receded near point of convergence (NPC), compared with healthy controls. Design: Cross-sectional study. Setting: Sports-medicine clinic. Participants: Patients examined after concussion (n = 33; mean ± SD = 7.2 ± 3.1 days) and a group of uninjured athletes (n = 31) completed a Postconcussion Symptom Scale, underwent NPC testing, and single/dual-task gait assessments. Independent Variables: Near point of convergence was defined as the patient-reported diplopia distance when a fixation target moved toward the nose. Receded NPC was defined as a distance >5 cm from the tip of the nose. Main Outcome Measures: Spatiotemporal gait characteristics in single-task and dual-task conditions were evaluated with analysis of variance; correlations were calculated between NPC and gait measures. Results: Eighteen of 33 (55%) patients with concussion presented with receded NPC. Those with receded NPC exhibited slower gait speed (single-task = 1.06 ± 0.14 m/s vs 1.19 ± 0.15 m/s; dual-task = 0.80 ± 0.13 m/s vs 0.94 ± 0.13 m/s; P = 0.003) and shorter stride lengths (single-task = 1.11 ± 0.10 m vs 1.24 ± 0.11 m; dual-task = 0.97 ± 0.11 m vs 1.09 ± 0.11 m; P = 0.001) than healthy controls. Near point of convergence was moderately correlated with dual-task average walking speed for the normal NPC group (ρ = −0.56; P = 0.05). Postconcussion Symptom Scale scores did not significantly differ between groups (27 ± 18 vs 28 ± 16). Conclusions: After concussion, adolescents with receded NPC exhibited significant gait-related deficits compared with healthy controls, whereas those with normal NPC did not. Vergence and gross motor system dysfunction may be associated after concussion. Gait and vergence measures may contribute useful information to postconcussion evaluations.https://ift.tt/2rN62sH
Physiotherapist-Led Physical Activity Interventions Are Efficacious at Increasing Physical Activity Levels: A Systematic Review and Meta-analysis
Objective: Physical activity (PA) interventions to address noncommunicable disease (NCD) risk are commonly delivered in private practice and outpatient physiotherapy settings. This study reviewed the efficacy of physiotherapist-led physical activity (PLPA) interventions at improving PA levels. Data sources: Twelve databases were searched using terms related to both physiotherapy and PA. English-language studies of all designs in adults were included. Meta-analyses were conducted separately for interventions measuring the following: (1) participants meeting recommended PA levels; (2) total PA at short- and long-term follow-up; and (3) total PA achieved after short and long PLPA interventions. Pooled effects were calculated using a fixed-effects model as standardized mean differences (SMDs). Nonstatistical analysis was used to identify the effect of PLPA interventions on the volume of PA performed at different intensities. Main Results: From an initial 4140 studies, 8 were retained, and risk of bias ranged from low to high. Meta-analysis showed the odds of adults meeting minimum recommended PA levels were doubled in groups provided a PLPA intervention [OR = 2.15, 95% confidence interval (CI) = 1.35-3.43]. Total PA levels were increased in the short term (SMD = 0.15, 95% CI = 0.03-0.27) but not in the long term. Longer term interventions did not improve outcomes. Nonstatistical analysis identified that PLPA interventions were efficacious at increasing the amount of PA adults performed at all intensities. Conclusions: Clinic-based PLPA interventions delivered in private practice, primary care, and outpatient settings were efficacious at increasing PA in adults at risk of NCDs. Improvements did not last long term and were not enhanced with longer interventions.https://ift.tt/2ItgiN4
Atopy in Elite Endurance Athletes
Objective: To assess the frequency of atopy (specific IgE levels), to evaluate the allergic symptoms using the Allergy Questionnaire for Athletes (AQUA), and to determine whether atopy is associated with allergic symptoms in elite endurance athletes. Design: Cross-sectional study. Setting: Assessments were performed at Hospital das Clinicas—São Paulo University Medical School. Participants: Fifty-nine elite endurance athletes (triathletes and runners). Main Outcome Measures: Allergic symptoms were assessed by a validated self-report AQUA questionnaire and atopy by specific IgE level. Results: The frequency of atopy (specific IgE to at least one inhalant allergen) and allergic symptoms was 57.6% and 54.2%, respectively. In addition, no association was observed between atopy and allergic symptoms. Conclusions: A possible implication from our results is that atopy screening in elite athletes should be performed using AQUA questionnaire and measuring specific IgE simultaneously.https://ift.tt/2rMB3Nj
Lightheadedness After Concussion: Not All Dizziness is Vertigo
Objective: To characterize the presence and degree of postconcussion lightheadedness in relation to postconcussion vertigo and dizziness, and to determine whether lightheadedness influences overall symptom duration. Design: Prospective, cohort design. Setting: Nationwide Children's Hospital, Sports Concussion Clinic. Participants: Five hundred ten patients (9-19 years of age) within 30 days of concussion injury. Main Outcome Measures: Patient ratings (scale 0-6) of multiple postconcussion symptoms including lightheadedness, vertigo, and dizziness, reported from the day of clinic evaluation and recalled from the day of concussion. Results: Postconcussion lightheadedness occurred commonly relative to vertigo. Lightheadedness was recalled more than vertigo (70.8% vs 48.6%, Phttps://ift.tt/2rLZmuy
Return to Driving After Hip Arthroscopy
Objective: The objective of this study was to evaluate patients' braking performance using a modern driving simulator after undergoing a right hip arthroscopy. Design: This prospective study included 5 total driving sessions at which measurements were taken. Setting: The study was conducted at an academic medical center. Patients: A total of 14 patients scheduled to undergo a right hip arthroscopy were enrolled and compared with a control group of 17 participants to account for a potential learning phenomenon. Interventions: Patients drove in the simulator preoperatively to establish a baseline, and then drove again at 2, 4, 6, and 8 weeks postoperatively. The control group did not undergo any type of surgical procedure. The main independent variable was time from surgery. Main Outcome Measures: A modern driving simulator was used to measure initial reaction time (IRT), throttle release time (TRT), foot movement time (FMT), and brake travel time (BTT). The braking reaction time (BRT) was calculated as the sum of IRT + TRT + FMT, and the total braking time (TBT) was calculated as the sum of BRT + BTT. Results: The experimental group showed no significant changes in BTT (P = 0.11, JOURNAL/cjspm/04.02/00042752-201805000-00009/math_9MM1/v/2018-05-15T044632Z/r/image-tiff = 0.04) nor TBT (P = 0.20, JOURNAL/cjspm/04.02/00042752-201805000-00009/math_9MM2/v/2018-05-15T044632Z/r/image-tiff = 0.03) over the duration of 8 weeks. Although the experimental group did exhibit significant improvements in IRT (P = 0.002), TRT (Phttps://ift.tt/2IpLxbK
Compression Socks Worn During Flight and Hemostatic Balance in Boston Marathon Runners on Oral Contraceptives
Objective: To investigate the effect of oral contraceptive (OC) use and compression socks on hemostatic activation in women flying cross-country to and from a marathon. Design: Prospective study. Setting: 2015 Boston Marathon. Participants: Women were divided into non-OC using (CONTROL; n = 12), OC-using (OC; n = 15), and OC-using plus compression sock (OC + SOCK; n = 14) groups. Intervention: Women in OC + SOCK wore compression socks during flights to and from the marathon. Main Outcome Measures: Venous blood samples were collected within 24 hours of arriving in Boston (EXPO), immediately after the marathon (RUN), and within 24 hours after a return flight home (Post-Flight) for analysis of thrombin–antithrombin complex (TAT), d-dimer, and tissue plasminogen activator (t-PA). Results: TAT did not increase with exercise (P = 0.48) and was not affected by group (P = 0.08) or the interaction between these 2 factors (P = 0.80). Group, time, and their interaction were significant for d-dimer (all Phttps://ift.tt/2rO0dLr
Quadriceps Tendon-Bone or Patellar Tendon-Bone Autografts When Reconstructing the Anterior Cruciate Ligament: A Meta-analysis
Objective: We aimed to quantitatively assess the outcomes of studies, comparing the use of Bone-patellar tendon-bone (BPTB) and the quadriceps tendon-bone (QTB) autografts when reconstructing the anterior cruciate ligament (ACL). Data Sources: MEDLINE, Embase, and CINAHL databases were searched for relevant articles published between January 1980 and January 2015 for the purpose of identifying studies comparing BPTB and QTB autografts for ACL reconstruction. Included studies were assessed regarding their methodological quality before analysis. Outcomes analyzed were graft failure rates, objective and subjective stability assessments, as well as the presence and severity of donor site morbidity. Main Results: Five studies contributed to the quantitative analysis of 806 patients with 452 patients included in the BPTB group and 354 patients in the QTB group. Graft failure rates were similar between the 2 groups [odds ratio (OR) = 0.61; confidence interval (CI) = 0.17-2.15; Z = 0.78, P = 0.44]. There were no significant differences between the 2 groups when testing anteroposterior stability using an arthrometer (standardized mean difference = 0.07; CI = −0.12-0.25; Z = 0.70, P = 0.48). At 1 year postoperatively, there was no difference in the percentage of patients with a positive pivot shift test between the 2 groups (OR = 1.0; CI = 0.85-1.18; Z = 0.01, P = 0.99). However, significantly less patients had graft site pain 1 year after surgery in the QTB group (OR = 0.10; CI = 0.02-0.43; Z = 3.12, P = 0.002). Similarly, fewer patients reported moderate to severe pain while kneeling, in the QTB group (OR = 0.16; CI = 0.07-0.37; Z = 4.26, Phttps://ift.tt/2IrjiJF
Trunk Side Strain Has a High Incidence in First-Class Cricket Fast Bowlers in Australia and England
Objective: To investigate the past incidence of side strain injury and its associated factors in first-class cricket fast bowlers in Australia and England. Design: Retrospective case series. Setting: Professional cricket. Participants: Cricket fast bowlers who were professionally contracted full time at first-class level in Australia and England in 2011. All bowlers were male and aged 18 or older. A bowler was defined as a fast bowler if the wicketkeeper would take their stance back from the stumps. There were 207 participants. Interventions: Not applicable. Main Outcome Measures: The association between bowling arm, player height, active trunk lateral flexion range of motion, side bridge endurance, volume of first-class cricket played, and the history of injury was determined. Results: Over half of the bowlers had sustained at least 1 side strain in their career. Seventy-seven percent of primary injuries occurred in bowlers aged 24 or under. A higher proportion of injured bowlers had reached first-class volume in their career. Recurrence occurred in 30% of bowlers, with over 30% of these bowlers sustaining at least 1 further recurrence. Nearly half of all recurrences occurred within 2 years with a further quarter in the next year. The injury was not associated with any measured factors. Conclusions: Side strain is a common injury among first-class cricket fast bowlers, especially at younger ages. It was associated with the volume of first-class cricket played. Recurrence was common and occurred most frequently in the first 2 years after primary injury.https://ift.tt/2IOQUVl
Underlying Chronic Disease, Medication Use, History of Running Injuries and Being a More Experienced Runner Are Independent Factors Associated With Exercise-Associated Muscle Cramping: A Cross-Sectional Study in 15778 Distance Runners
Background: Exercise-associated muscle cramping (EAMC) is a significant medical complication in distance runners, yet factors associated with EAMC are poorly documented. Objective: To document risk factors associated with EAMC in runners. Design: Cross-sectional study. Setting: Two ocean races (21.1 km, and 56 km). Participants: Fifteen thousand seven hundred seventy-eight race entrants. Methods: Participants completed a prerace medical history screening tool including: training, cardiovascular disease (CVD), risk factors for, and symptoms of CVD, history of diseases affecting major organ systems, cancer, allergies, medication use, and running injury. Runners were grouped as having a history of EAMC (hEAMC group = 2997) and a control group (Control = 12 781). Results: Independent factors associated with a higher prevalence ratio (PR) of hEAMC were any risk factor for CVD (PR = 1.16; P = 0.0002), symptoms of CVD (PR = 2.38; Phttps://ift.tt/2rO04HT
Cancers, Vol. 10, Pages 144: Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro
Cancers, Vol. 10, Pages 144: Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro
Cancers doi: 10.3390/cancers10050144
Authors: Rodolfo Garza-Morales Roxana Gonzalez-Ramos Akiko Chiba Roberto Montes de Oca-Luna Lacey R. McNally Kelly M. McMasters Jorge G. Gomez-Gutierrez
Triple-negative breast cancer (TNBC) is one of the most aggressive types of cancer, and treatment is limited to chemotherapy and radiation. Oncolytic virotherapy may be a promising approach to treat TNBC. However, oncolytic adenovirus (OAd)-based mono-therapeutic clinical trials have resulted in modest outcomes. The OAd potency could be increased by chemotherapy-induced autophagy, an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. In this study, the ability of alkylating agent temozolomide (TMZ)-induced autophagy to increase OAd replication and oncolysis in TNBC cells was evaluated. Human TNBC MDA-MB-231 and HCC1937 cells and mouse 4T1 cells were infected with an OAd expressing the red fluorescent protein mCherry on the virus capsid (OAdmCherry) alone or in combination with TMZ. TNBC cells treated with OAdmCherry/TMZ displayed greater mCherry and adenovirus (Ad) early region 1A (E1A) expression and enhanced cancer-cell killing compared to OAdmCherry or TMZ alone. The combined therapy-mediated cell death was associated with virus replication and accumulation of the autophagy marker light chain 3 (LC3)-II. Overall, this study provides experimental evidence of TMZ’s ability to increase oncolytic virotherapy in both human and murine TNBC cells.
https://ift.tt/2IIClCC
Increase of frontal neuronal activity in chronic neglect after training in virtual reality
Acta Neurologica Scandinavica, EarlyView.
https://ift.tt/2Iug4Fc
Outcome in lacunar stroke: A cohort study
Acta Neurologica Scandinavica, EarlyView.
https://ift.tt/2IKUm3j
Impact of Zika Virus on adult human brain structure and functional organization
Annals of Clinical and Translational Neurology, EarlyView.
https://ift.tt/2rNkZuN
Predominantly cystic clear cell renal cell carcinoma and multilocular cystic renal neoplasm of low malignant potential form a low-grade spectrum
Abstract
Multilocular cystic renal cell carcinoma has been recently excluded from clear cell renal cell carcinoma (CCRCC) category and re-designated as multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) due to its uniformly good outcomes. While strict distinction between MCRNLMP from predominantly cystic CCRCC (pc-CCRCC) is being emphasized, the significance of extensive true cystic component in CCRCC has not been investigated. Herein, we analyzed 57 MCRNLMP, 69 pc-CCRCC, and 46 non-cystic CCRCC. There were no statistically significant differences between the three subtypes in age, gender, and laterality. ISUP grades were 1 (73%) or 2 (27%) for MCRNLMP; for pc-CCRCC were 1 (31%), 2 (60%), and 3 (9%); and for non-cystic CCRCC were 1 (9%), 2 (52%), 3 (26%), and 4 (13%). MCRNLMP were either pT stage 1 (91%) or 2 (9%), pT stages for pc-CCRCC were 1 (92.5%), 2 (1.5%), and 3 (6%) and for non-cystic CCRCC were 1 (58.7%), 2 (6.5%), and 3 (34.8%). None of MCRNLMP patients developed recurrences or metastases, and only 1 contralateral kidney tumor and 1 metastasis developed in pc-CCRCC. In contrast, 19 patients with non-cystic CCRCC developed metastases (5-year PFS 58%, CI 38.3–73.5%), and 1 patient died of disease. Monosomy 3 was common in both MCRNLMP (3/3) and pc-CCRCC (6/7). This large series of MCRNLMP confirms its indolent behavior, shows that pc-CCRCC has significantly better prognosis than non-cystic CCRCC and may define the lower grade spectrum of CCRCC. We recommend that the presence and extent of CCRCC cystic component should be documented in the pathology report.
https://ift.tt/2rL6TZO
Quality of life and patients’ expectations in soft tissue sarcoma
Future Oncology, Volume 14, Issue 10s, Page 51-62, May 2018.
https://ift.tt/2IInjwR
Options for treating different soft tissue sarcoma subtypes
Future Oncology, Volume 14, Issue 10s, Page 25-49, May 2018.
https://ift.tt/2wK90D7
The key role of pathology, surgery and radiotherapy in the initial management of soft tissue sarcoma
Future Oncology, Volume 14, Issue 10s, Page 15-23, May 2018.
https://ift.tt/2IOsP0K
Getting up-to-date in the management of soft tissue sarcoma
Future Oncology, Volume 14, Issue 10s, Page 3-13, May 2018.
https://ift.tt/2IGvjOX
Autoregulation in the Neuro ICU
Abstract
Purpose of review
The purpose of this review is to briefly describe the concept of cerebral autoregulation, to detail several bedside techniques for measuring and assessing autoregulation, and to outline the impact of impaired autoregulation on clinical and functional outcomes in acute brain injury. Furthermore, we will review several autoregulation studies in select forms of acute brain injuries, discuss the potential for its use in patient management in the ICU, and suggest further avenues for research.
Recent findings
Cerebral autoregulation plays a critical role in regulating cerebral blood flow, and impaired autoregulation has been associated with worse functional and clinical outcomes in various acute brain injuries. There exists a multitude of methods to assess the autoregulatory state in patients using both invasive and non-invasive modalities. Continuous monitoring of patients in the ICU has yielded autoregulatory-derived optimal perfusion pressures that may prevent secondary injury and improve outcomes.
Summary
Measuring autoregulation continuously at the bedside is now a feasible option for clinicians working in the ICU, although there exists a great need to standardize autoregulatory measurement. While the clinical benefits await prospective and randomized trials, autoregulation-derived parameters show enormous potential for creating an optimal physiological environment for the injured brain.
https://ift.tt/2IuPAUk
Numerical approximation of the electromechanical coupling in the left ventricle with inclusion of the Purkinje network
International Journal for Numerical Methods in Biomedical Engineering, EarlyView.
https://ift.tt/2IpaK5Z
A Genome-Wide Assay Specifies Only GreA as a Transcription Fidelity Factor in Escherichia coli
Although mutations are the basis for adaptation and heritable genetic change, transient errors occur during transcription at rates that are orders of magnitude higher than the mutation rate. High rates of transcription errors can be detrimental by causing the production of erroneous proteins that need to be degraded. Two transcription fidelity factors, GreA and GreB, have previously been reported to stimulate the removal of errors that occur during transcription, and a third fidelity factor, DksA, is thought to decrease the error rate through an unknown mechanism. Because the majority of transcription-error assays of these fidelity factors were performed in vitro and on individual genes, we measured the in vivo transcriptome-wide error rates in all possible combinations of mutants of the three fidelity factors. This method expands measurements of these fidelity factors to the full spectrum of errors across the entire genome. Our assay shows that GreB and DksA have no significant effect on transcription error rates, and that GreA only influences the transcription error rate by reducing G-to-A errors.
https://ift.tt/2rNCtqS
Key Transport and Ammonia Recycling Genes Involved in Aphid Symbiosis Respond to Host-Plant Specialization
Microbes are known to influence insect-plant interactions; however, it is unclear if host-plant diet influences the regulation of nutritional insect symbioses. The pea aphid, Acyrthosiphon pisum, requires its nutritional endosymbiont, Buchnera, for the production of essential amino acids. We hypothesize that key aphid genes that regulate the nutritional symbioses respond to host-plant diet when aphids feed on a specialized (alfalfa) compared to a universal host-plant diet (fava), which vary in amino acid profiles. Using RNA-Seq and whole genome bisulfite sequencing, we measured gene expression and DNA methylation profiles for such genes when aphids fed on either their specialized or universal host-plant diets. Our results reveal that when aphids feed on their specialized host-plant they significantly up-regulate and/or hypo-methylate key aphid genes in bacteriocytes related to the amino acid metabolism, including glutamine synthetase in the GOGAT cycle that recycles ammonia into glutamine and the glutamine transporter ApGLNT1. Moreover, regardless of what host-plant aphids feed on we observed significant up-regulation and differential methylation of key genes involved in the amino acid metabolism and the glycine/serine metabolism, a metabolic program observed in proliferating cancer cells potentially to combat oxidative stress. Based on our results, we suggest that this regulatory response of key symbiosis genes in bacteriocytes allows aphids to feed on a suboptimal host-plant that they specialize on.
https://ift.tt/2wIw3hw
Assessment of an Organ-Specific de Novo Transcriptome of the Nematode Trap-Crop, Solanum sisymbriifolium
Solanum sisymbriifolium, also known as "Litchi Tomato" or "Sticky Nightshade," is an undomesticated and poorly researched plant related to potato and tomato. Unlike the latter species, S. sisymbriifolium induces eggs of the cyst nematode, Globodera pallida, to hatch and migrate into its roots, but then arrests further nematode maturation. In order to provide researchers with a partial blueprint of its genetic make-up so that the mechanism of this response might be identified, we used single molecule real time (SMRT) sequencing to compile a high quality de novo transcriptome of 41,189 unigenes drawn from individually sequenced bud, root, stem, and leaf RNA populations. Functional annotation and BUSCO analysis showed that this transcriptome was surprisingly complete, even though it represented genes expressed at a single time point. By sequencing the 4 organ libraries separately, we found we could get a reliable snapshot of transcript distributions in each organ. A divergent site analysis of the merged transcriptome indicated that this species might have undergone a recent genome duplication and re-diploidization. Further analysis indicated that the plant then retained a disproportionate number of genes associated with photosynthesis and amino acid metabolism in comparison to genes with characteristics of R-proteins or involved in secondary metabolism. The former processes may have given S. sisymbriifolium a bigger competitive advantage than the latter did.
https://ift.tt/2IPG01K
In vitro priming of adoptively transferred T cells with a ROR{gamma} agonist confers durable memory and stemness in vivo
Adoptive T cell transfer therapy is an FDA-approved treatment for leukemia that relies on the ex vivo expansion and re-infusion of a patient's immune cells, which can be engineered with a chimeric antigen receptor (CAR) for more efficient tumor recognition. Type 17 T cells, controlled transcriptionally by RORγ, have been reported to mediate potent anti-tumor effects superior to those observed with conventionally expanded T cells. Here we demonstrate that addition of a synthetic, small molecule RORγ agonist during ex vivo expansion potentiates the anti-tumor activity of human Th17 and Tc17 cells redirected with a CAR. Likewise, ex vivo use of this agonist bolstered the anti-tumor properties of murine tumor-specific CD4+ and CD8+ T cells. Expansion in the presence of the RORγ agonist enhanced IL-17A production without compromising IFN-γ secretion in vitro. In vivo, cytokine neutralization studies revealed that IFN-γ and IL-17A were required to regress murine melanoma tumors. The enhanced anti-tumor effect of RORγ agonist treatment was associated with recovery of more donor T cells in the tumor and spleen; these cells produced elevated levels of cytokines months after infusion and expressed markers of long-lived stem and central memory cells such as Tcf7 and CD62L. Conversely, untreated cells mainly exhibited effector phenotypes in the tumor. Cured mice previously treated with agonist-primed T cells were protected from tumor re-challenge. Collectively, our work reveals that in vitro treatment with a RORγ agonist generates potent anti-tumor Type 17 effector cells that persist as long-lived memory cells in vivo.
https://ift.tt/2IqTvFL
Long chain n-3 fatty acids attenuate oncogenic KRas-driven proliferation by altering plasma membrane nanoscale proteolipid composition
Ras signaling originates from transient nanoscale compartmentalized regions of the plasma membrane composed of specific proteins and lipids. The highly specific lipid composition of these nanodomains, termed nanoclusters, facilitates effector recruitment and therefore influences signal transduction. This suggests that Ras nanocluster proteolipid composition could represent a novel target for future chemoprevention interventions. There is evidence that consumption of fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) such as eicosapentaenoic acid (EPA, 20:5Δ5,8,11,14,17) and docosahexaenoic acid (DHA, 22:6Δ4,7,10,13,16,19) may reduce colon cancer risk in humans, yet the mechanism underlying this effect is unknown. Here we demonstrate that dietary n-3 PUFA reduce the lateral segregation of cholesterol-dependent and -independent nanoclusters, suppressing phosphatidic acid-dependent oncogenic KRas effector interactions, via their physical incorporation into plasma membrane phospholipids. This results in attenuation of oncogenic Ras-driven colonic hyperproliferation in both Drosophila and murine models. These findings demonstrate the unique properties of dietary n-3 PUFA in the shaping of Ras nanoscale proteolipid complexes and support the emerging role of plasma membrane-targeted therapies.
https://ift.tt/2rN5VMN
Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients
Hyperpolarized (HP) magnetic resonance imaging using [1-13C] pyruvate is a novel method that can characterize energy metabolism in the human brain and brain tumors. Here we present the first dynamically acquired human brain HP 13C metabolic spectra and spatial metabolite maps in cases of both untreated and recurrent tumors. In vivo production of HP lactate from HP pyruvate by tumors was indicative of altered cancer metabolism, while production of HP lactate in the entire brain was likely due to baseline metabolism. We correlated our results with standard clinical brain MRI, MRI DCE perfusion, and in one case FDG PET/CT. Our results suggest that HP 13C pyruvate-to-lactate conversion may be a viable metabolic biomarker for assessing tumor response.
https://ift.tt/2L6B0E7
Mathematical modeling predicts response to chemotherapy and drug combinations in ovarian cancer
Platinum-based chemotherapy constitutes the backbone of clinical care in advanced solid cancers such as high-grade serous ovarian cancer (HGSOC) and has prolonged survival of millions of cancer patients. Most of these patients, however, become resistant to chemotherapy, which generally leads to a fatal refractory disease. We present a comprehensive stochastic mathematical model and simulator approach to describe platinum resistance and standard-of-care (SOC) therapy in HGSOC. We used pre- and post-treatment clinical data, including 18F-FDG-PET/CT images, to reliably estimate the model parameters and simulate "virtual HGSOC patients." Treatment responses of the virtual patients generated by our mathematical model were indistinguishable from real-life HGSOC patients. We demonstrated the utility of our approach by evaluating the survival benefit of combination therapies that contain up to six drugs targeting platinum resistance mechanisms. Several resistance mechanisms were already active at diagnosis, but combining SOC with a drug that targets the most dominant resistance subpopulation resulted in a significant survival benefit. This work provides a theoretical basis for a cancer treatment paradigm in which maximizing platinum's killing effect on cancer cells requires overcoming resistance mechanisms with targeted drugs. This freely available mathematical model and simulation framework enable rapid and rigorous evaluation of the benefit of a targeted drug or combination therapy in virtual patients before clinical trials, which facilitates translating preclinical findings into clinical practice.
https://ift.tt/2rPaTZm
Cancer-associated fibroblasts drive glycolysis in a targetable signaling loop implicated in head and neck squamous cell carcinoma progression
Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted hepatocyte growth factor (HGF) facilitates HNSCC progression, however very little is known about the role of CAFs in HNSCC metabolism. Here we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis. CAF-secreted HGF induced basic fibroblast growth factor (bFGF) secretion from HNSCC. CAFs were more efficient than HNSCC in using lactate as a carbon source. HNSCC-secreted bFGF increased mitochondrial oxidative phosphorylation (OXPHOS) and HGF secretion from CAFs. Combined inhibition of c-Met and FGFR significantly inhibited CAF-induced HNSCC growth in vitro and in vivo (p<0.001). Our cumulative findings underscore reciprocal signaling between CAF and HNSCC involving bFGF and HGF. This contributes to metabolic symbiosis and a targetable therapeutic axis involving c-Met and FGFR.
https://ift.tt/2L8q7kX
An in vivo screen identifies PYGO2 as a driver for metastatic prostate cancer
Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen. Among the top positive hits, we conducted an in-depth functional analysis on Pygopus family PHD finger 2 (PYGO2), located in the amplicon at 1q21.3. PYGO2 overexpression enhances primary tumor growth and local invasion to draining lymph nodes. Conversely, PYGO2 depletion inhibits prostate cancer cell invasion in vitro and progression of primary tumor and metastasis in vivo. In clinical samples, PYGO2 upregulation associated with higher Gleason score and metastasis to lymph nodes and bone. Silencing PYGO2 expression in patient-derived xenograft models impairs tumor progression. Lastly, PYGO2 is necessary to enhance the transcriptional activation in response to ligand-induced Wnt/β-catenin signaling. Together, our results indicate that PYGO2 functions as a driver oncogene in the 1q21.3 amplicon and may serve as a potential prognostic biomarker and therapeutic target for metastatic prostate cancer.
https://ift.tt/2rMPWhS
Osteocyte-Driven Downregulation of Snail Restrains Effects of Drd2 Inhibitors on Mammary Tumor Cells
While bone is a frequent target of breast cancer-associated metastasis, little is known about the effects of tumor-bone interactions on the efficacy of tumor-suppressing agents. Here we examined the effect of two FDA-approved dopamine modulators, Fluphenazine (FP) and Trifluoperazine (TFP), on mammary tumor cells, osteoclasts, osteoblasts, and osteocytes. These agents suppressed proliferation and migration of mammary tumor cells chiefly by antagonizing dopamine receptor D2 and reduced bone resorption by downregulating nuclear factor of activated T-cells, cytoplasmic 1 (Nfatc1). Three-dimensional spheroid formation assays revealed that tumor cells have high affinity to osteocytes and type I collagen, and interactions with osteocytes as well as administration of FP and TFP downregulated Snail and suppressed migratory behaviors. Unlike the inhibitory action of FP and TFP on tumor growth, tumor-osteocyte interactions stimulated tumor proliferation by upregulating NFκB and Akt. In the bone microenvironment, osteocytes downregulated Snail and acted as an attractant as well as a stimulant to mammary tumor cells. These results demonstrate that tumor-osteocyte interactions strengthen dopamine receptor-mediated suppression of tumor migration but weaken its inhibition of tumor proliferation in the osteocyte-rich bone microenvironment.
https://ift.tt/2IqNOqY
Explaining Resistance to CAR T Cells [News in Brief]
Memory T-cell phenotype more common in patients who have complete remission.
https://ift.tt/2IqTilX
Little Benefit to Breakthrough Cancer Drugs [News in Brief]
Approved more quickly, breakthrough therapies no more effective, safe, or novel than drugs approved via traditional pathway, study finds.
https://ift.tt/2GqswUz
Addition of Cannabidiol May Cut Drop Seizures in Lennox-Gastaut
WEDNESDAY, May 16, 2018 -- The addition of cannabidiol to conventional antiepileptic medication is associated with a reduction in the frequency of drop seizures among patients with Lennox-Gastaut syndrome, according to a study published in the May...
https://ift.tt/2IOHclG
Better Diet Quality Associated With Larger Brain Volume
WEDNESDAY, May 16, 2018 -- Better diet quality, including high intake of vegetables, fruit, whole grains, dairy, nuts, and fish, is associated with larger brain volume, according to a study published online May 16 in Neurology. Pauline H. Croll,...
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New Rabies Test Could Radically Change Testing, Treatment
WEDNESDAY, May 16, 2018 -- A new rapid rabies test for animals could revolutionize screening and spare humans unnecessary painful treatment, according to a U.S. Centers for Disease Control and Prevention study published online May 16 in PLOS...
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Nonprofit Manufacturer Could Keep Generic Drug Costs Down
WEDNESDAY, May 16, 2018 -- A nonprofit manufacturer could help keep generic drug prices down and maintain their supply, according to a perspective piece published in the May 17 issue of the New England Journal of Medicine. Dan Liljenquist, J.D.,...
https://ift.tt/2KxxHVt
Infusion of alloanergized donor lymphocytes after CD34-selected haploidentical myeloablative hematopoietic stem cell transplantation
Purpose: Allogeneic haematopoietic stem-cell transplantation (HSCT) is a curative treatment for many haematologic cancers. Use of haploidentical (mismatched) donors increases HSCT availability but is limited by severe graft-versus-host disease (GvHD) and delayed immune reconstitution. Alloanergization of donor T-cells is a simple approach to rebuild immunity whilst limiting GvHD after haploidentical HSCT but the optimal T-cell dose and impact on immune reconstitution remain unknown. Experimental Design: We performed a multicentre Phase 1 trial of alloanergized donor lymphocyte infusion (aDLI) after CD34-selected myeloablative haploidentical HSCT. The primary aim was feasibility and safety with secondary aims of assessing the less frequently addressed issue of impact on immune reconstitution. Results: Nineteen high-risk acute leukemia or myelodysplasia patients were enrolled. Engraftment occurred in 18/19 patients (95%). Pre-aDLI, twelve patients (63%) had bacteremia, 9/17 at-risk patients (53%) reactivated CMV and one developed acute GvHD. Sixteen patients received aDLI at dose-levels 1 (103 T-cells/kg, n=4), 2 (104, n=8), and 3 (105, n=4). Post-aDLI, 5 patients developed clinically significant acute GvHD and 4/14 at-risk patients (29%) reactivated CMV. T-cell recovery was significantly greater and functional virus- and tumor-associated antigen-specific T-cells were detectable earlier in patients receiving dose-level 2 or 3 vs dose-level 1/no aDLI. Alloanergization of donor cells expanded the CD4+ T-regulatory cell frequency within aDLI which increased further in vivo without impeding expansion of virus- and tumor-associated antigen-specific T-cells. Conclusions: These data demonstrate safety and a potential role for aDLI in contributing to immune reconstitution and expanding tolerogenic regulatory T-cells in vivo after CD34-selected myeloablative haploidentical HSCT.
https://ift.tt/2IorGd2
Mitigating SOX2-potentiated immune escape of Head and Neck Squamous Cell Carcinoma with a STING-inducing nanosatellite vaccine
Purpose: The response rates of Head and Neck Squamous Cell Carcinoma (HNSCC) to checkpoint blockade are below 20%. We aim to develop a mechanism-based vaccine to prevent HNSCC immune escape. Experimental Design: We performed RNA-Seq of sensitive and resistant HNSCC cells to discover central pathways promoting resistance to immune killing. Using biochemistry, animal models, HNSCC microarray and immune cell deconvolution, we assessed the role of SOX2 in inhibiting STING-type I interferon (IFN-I) signaling-mediated anti-tumor immunity. To bypass SOX2-potentiated STING suppression, we engineered a novel tumor antigen-targeted nanosatellite vehicle to enhance the efficacy of STING agonist and sensitize SOX2-expressing HNSCC to checkpoint blockade. Results: The DNA-sensing defense response is the most suppressed pathway in immune-resistant HNSCC cells. We identified SOX2 as a novel inhibitor of STING. SOX2 facilitates autophagy-dependent degradation of STING and inhibits IFN-I signaling. SOX2 potentiates an immunosuppressive microenvironment and promotes HNSCC growth in vivo in an IFN-I-dependent fashion. Our unique nanosatellite vehicle significantly enhances the efficacy of STING agonist. We show that the E6/E7-targeted nanosatellite vaccine expands the tumor-specific CD8+ T-cells by over 12-fold in the tumor microenvironment and reduces tumor burden. A combination of nanosatellite vaccine with anti-PD-L1 significantly expands tumor-specific CTL and limits the populations expressing markers for exhaustion, resulting in more effective tumor control and improved survival. Conclusion: SOX2 dampens the immunogenicity of HNSCC by targeting the STING pathway for degradation. The nanosatellite vaccine offers a novel and effective approach to enhance the adjuvant potential of STING agonist and break cancer tolerance to immunotherapy.
https://ift.tt/2k1od9C
Time-to-event Bayesian Optimal Interval Design to Accelerate Phase I Trials
Late-onset toxicity is common for novel molecularly targeted agents and immunotherapy. It causes major logistic difficulty for existing adaptive phase I trial designs, which require the observance of toxicity early enough to apply dose escalation rules for new patients. The same logistic difficulty arises when the accrual is rapid. We propose the time-to-event Bayesian optimal interval (TITE-BOIN) design to accelerate phase I trials by allowing for real-time dose assignment decisions for new patients while some enrolled patients' toxicity data are still pending. Similar to the rolling six design, the TITE-BOIN dose escalation/de-escalation rule can be tabulated before the trial begins, making it transparent and simple to implement, but is more flexible in choosing the target DLT rate and has higher accuracy to identify the MTD. Compared to the more complicated model-based time-to-event continuous reassessment method (TITE-CRM), the TITE-BOIN has comparable accuracy to identify the MTD, but is simpler to implement with substantially better overdose control. As the TITE-CRM is more aggressive, it is less likely to underdose patients. A numerical study shows that the TITE-BOIN design supports continuous accrual, without sacrificing patient safety nor the accuracy of identifying the MTD, and therefore has great potential to accelerate early phase drug development.
https://ift.tt/2Iprr1i
Playing the melanoma endgame
Treatments for melanoma are of two main types: targeted therapies and immune checkpoint inhibitors. However, both are only effective in a subset of patients and are limited by acquired resistance. Here, the authors present the preclinical basis to broadly target different forms of therapy-resistant melanoma.
https://ift.tt/2k5B9vc
Targeting the IDH2 Pathway in Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis. A large percentage of patients succumb to this disease, in spite of aggressive treatments with chemotherapy. Recent advances with mutational analysis led to the discovery of isocitrate dehydrogenase (IDH) mutations in AML. IDH2 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate; its mutated version leads to the accumulation of the oncometabolite (R)-2 hydroxyglutarate, which disrupts several cell processes and leads to a blockage in differentiation. Targeting IDH2 is compelling, as it is an early and stable mutation in AML. Enasidenib, a specific small molecule inhibitor of IDH2, recently gained FDA approval for the treatment of patients with relapsed/refractory IDH2-mutated AML. In this review, we will focus on the indications and efficacy of enasidenib in the treatment of IDH2-mutated AML patients.
https://ift.tt/2Ip2EKJ
Comment on 'Domestic light at night and breast cancer risk: a prospective analysis of 105 000 UK women in the Generations Study'
Comment on 'Domestic light at night and breast cancer risk: a prospective analysis of 105 000 UK women in the Generations Study'
Comment on 'Domestic light at night and breast cancer risk: a prospective analysis of 105 000 UK women in the Generations Study', Published online: 17 May 2018; doi:10.1038/s41416-018-0060-7
Comment on 'Domestic light at night and breast cancer risk: a prospective analysis of 105 000 UK women in the Generations Study'https://ift.tt/2IHYQrk
Reply to ‘Comment on ‘Domestic light at night and breast cancer risk: a prospective analysis of 105 000 UK women in the Generations Study”
Reply to 'Comment on 'Domestic light at night and breast cancer risk: a prospective analysis of 105 000 UK women in the Generations Study"
Reply to 'Comment on 'Domestic light at night and breast cancer risk: a prospective analysis of 105 000 UK women in the Generations Study", Published online: 17 May 2018; doi:10.1038/s41416-018-0092-z
Reply to 'Comment on 'Domestic light at night and breast cancer risk: a prospective analysis of 105 000 UK women in the Generations Study"https://ift.tt/2wMFxZa
A Comprehensive Evaluation of the Predictive Abilities of Fetal Electrocardiogram-Derived Parameters during Labor in Newborn Acidemia: Our Institutional Experience
This study aimed to identify cardiotocography patterns that discriminate fetal acidemia newborns by comprehensively evaluating the parameters obtained from Holter monitoring during delivery. Between June 1, 2015, and August 1, 2016, a prospective observational study of 85 patients was conducted using fetal Holter monitoring at the Beijing Obstetrics and Gynecology Hospital, Capital Medical University, China. Umbilical cord blood was sampled immediately after delivery and fetal acidemia was defined as umbilical cord arterial blood pH 0.50), STV (AUC = 0.84, ), DC (AUC = 0.84, ), AC (AUC = 0.80, ), and PELV (AUC = 0.71, ) were more strongly associated with fetal acidemia. Our institutional experience suggests that FECG-derived parameters from Holter monitoring are beneficial in reducing the incidence of neonatal acidemia.
https://ift.tt/2k1EnQj
Using CRISPR/Cas9 to Knock out Amylase in Acinar Cells Decreases Pancreatitis-Induced Autophagy
Pancreatic cancer is a malignant neoplasm that originates from acinar cells. Acinar cells get reprogrammed to become duct cells, resulting in pancreatic cancer. Pancreatitis is an acinar cell inflammation, leading to "impaired autophagy flux". Pancreatitis promotes acinar-to-ductal transdifferentiation. Expression of amylase gets eliminated during the progression of pancreatic cancer. Amylase is considered as an acinar cell marker; however, its function in cells is not known. Thus, we investigated whether amylase affects the acinar cell autophagy and whether it plays any role in development of pancreatitis. Here, we knocked out ATG12 in a pancreatic cancer cells and acinar cells using CRISPR/Cas9. Autophagy inhibition led to an increase in the expression of duct cell markers and a simultaneous decrease in that of acinar cell markers. It also caused an increase in cell viability and changes in mitochondrial morphology. Next, we knocked out amylase in acinar cells. Amylase deficiency decreased autophagy induced by pancreatitis. Our results suggest that amylase controls pancreatitis-induced autophagy. We found that eliminating amylase expression contributes to pancreatic cancer etiology by decreasing autophagy. Furthermore, our results indicate that amylase plays a role in selective pancreatitis-induced autophagy of pancreatic enzyme vesicles.
https://ift.tt/2k2WMvZ
Going Bone Deep: Osseous Rosai–Dorfman Disease in an Adult with Recurrent, Culture-Negative Osteomyelitis
A patient presented for medical care on three separate occasions over the course of two years with recurrent right knee pain attributed to chronic osteomyelitis. Careful assessment revealed that his symptoms were caused by osseous Rosai–Dorfman disease. This case presents an alternative diagnostic possibility for culture-negative chronic osteomyelitis.
https://ift.tt/2IuqX9Z
A systematic review of physical activity-based behaviour change interventions reaching men with prostate cancer
Abstract
Purpose
Men who are survivors of prostate cancer report a variety of psychological and physical factors contributing to a lower quality of life, and physical activity can assist to mitigate these issues. This review aims to provide a summary of physical activity behaviour change trials targeting prostate cancer survivors, assess the feasibility of these interventions and, if possible, identify intervention and study characteristics associated with significant intervention effects.
Method
Four databases (PubMed, CINAHL, PsycINFO and EMBASE) were systematically searched for randomised controlled trials containing at least one behavioural outcome relating to physical activity published up until July 2016. Forward and backwards, hand, key author citation searching and known research were also considered.
Results
From a total of 13, 828 titles, the search resulted in 12 studies (6 prostate cancer only and 6 mixed cancer interventions), eight of which found positive results most often related immediately to post-intervention aerobic activity. Factors relating to efficacy were not conclusive due to the heterogeneity of studies and lack of cancer-specific data in mixed cancer trials. Future research focusing on intervention reach, maintenance of intervention effects and resistance training outcomes is needed.
Conclusion
There is preliminary evidence to suggest that a variety of physical activity behaviour change interventions targeting men with a history of prostate cancer can be efficacious, at least in the short term. Experimental studies are required to identify key intervention features.
Implications for Cancer Survivors
Physical activity interventions can assist prostate cancer survivors in relation to short-term lifestyle change, though more evidence is required to improve the clarity of factors related to efficacy.
https://ift.tt/2wMub7A
The relationship between physical impairments, quality of life and disability of the neck and upper limb in patients following neck dissection
Abstract
Purpose
The purpose of this study was to examine the relationship between physical impairments, quality of life and disability in patients following neck dissection, with consideration of patient and clinical characteristics.
Methods
Cross-sectional study of patients < 5 years after neck dissection for head and neck cancer. Quality of life and self-reported disability were measured with the Neck Dissection Impairment Index, Quick Disabilities of the Arm, Shoulder and Hand, and Neck Disability Index. Active neck and shoulder range of motion and isometric muscle strength were also assessed. Generalised linear modelling was used to explore relationships between variables.
Results
Eighty-four participants (68% male, median age 61 years) demonstrated reduced quality of life (median (interquartile range) score = 76 (49, 93) from 0 (worst) to 100 (best)), and mild levels of upper limb (14 (2, 32)) and neck disability (14 (6, 28)) (from 0 (best) to 100 (worst)). Bilateral neck dissection was associated with reduced quality of life (coeff (95% CI) = − 12.49 (− 24.69, − 0.29)). Post-operative chemoradiation therapy was associated with reduced quality of life (− 21.46 (− 37.57, − 5.35)) and neck disability (0.71 (0.10, 1.32)). Measures of shoulder flexibility or strength were associated with quality of life and self-reported disability.
Conclusions
Quality of life and musculoskeletal disability after neck dissection are associated with factors from multiple domains including physical motor function and treatment modality.
Implications for Cancer Survivors
Having reduced shoulder flexibility or strength is related to functional deficits and quality of life after neck dissection for head and neck cancer.
https://ift.tt/2rHFucf
Weight-Loss Cognitive-Behavioural Treatment and Essential Amino Acid Supplementation in a Patient with Spinal Muscular Atrophy and Obesity
Spinal muscular atrophy is a genetic neuromuscular disease characterised by muscle atrophy, hypotonia, weakness, and progressive paralysis. Usually, these patients display increased fat mass deposition and reductions in fat-free mass and resting energy expenditure—an unfavourable condition that facilitates the development of obesity. However, weight management of these patients remains poorly described. Hence, the aim of this case report was to describe the clinical presentation and weight management of a 31-year-old male patient with spinal muscular atrophy type III, class I obesity, and metabolic syndrome treated for 1 year by means of a personalised multistep cognitive-behavioural treatment for obesity. The treatment produced a weight loss of 7.2 kg (7.1%), which was associated with a marked improvement in both the patient's self-reported general conditions and obesity-related cardiometabolic profile, and no adverse effects in terms of spinal muscular atrophy (i.e., reductions in fat-free mass or resting energy expenditure).
https://ift.tt/2rMbcVL
The Surgeon Volume-outcome Relationship: Not Yet Ready for Policy
Objective: Increasing surgeon volume may improve outcomes for index operations. We hypothesized that there may be surrogate operative experiences that yield similar outcomes for surgeons with a low-volume experience with a specific index operation, such as esophagectomy. Background: The relationship between surgeon volume and outcomes has potential implications for credentialing of surgeons. Restrictions of privileges based on surgeon volume are only reasonable if there is no substitute for direct experience with the index operation. This study was aimed at determining whether there are valid surrogates for direct experience with a sample index operation—open esophagectomy. Methods: The Nationwide Inpatient Sample (2003–2009) was utilized. Surgeons were stratified into low and high-volume groups based on annual volume of esophagectomy. Surrogate volume was defined as the aggregate annual volume per surgeon of upper gastrointestinal operations including excision of esophageal diverticulum, gastrectomy, gastroduodenectomy, and repair of diaphragmatic hernia. Results: In all, 26,795 esophagectomies were performed nationwide (2003–2009), with a crude inhospital mortality rate of 5.2%. Inhospital mortality decreased with increasing volume of esophagectomies performed annually: 7.7% and 3.8% for low and high-volume surgeons, respectively (Phttps://ift.tt/2GQkpWK
Effect of cilostazol in experimental model of degloving injuries in rat limbs
Abstract Purpose: To evaluate the effect of the cilostazol on the evolution of partially avulsed flaps, using experimental model of cutaneous degloving in rat limbs. Methods: A controlled and randomized experimental study was carried out in which the blood flow and the percentage of flap necrosis were evaluated. We compared the study group, which received cilostazol, and the control group, which received enteral saline solution in the postoperative period. The blood flow in the flap was evaluated through Laser Doppler flowmetry, and a planimetry using the IMAGE J® software was employed for the calculation of the area of necrosis. Results: Enteral administration of cilostazol was associated with a higher mean blood flow in all regions of the flap, with a statistically significant difference in the proximal and middle regions (p<0.001) and a lower percentage of necrotic area in the flap (p<0.001). Conclusion: Postoperative enteral administration of cilostazol increased blood flow and decreased the total area of necrosis of avulsed cutaneous flaps of rat limbs.
https://ift.tt/2rP9RfZ
Investigation of the effect of gestational diabetes on fetal cardiac tissue in streptozotocin ınduced in rats
Abstract Purpose: To investigate the cause of congenital anomalies resulted from gestational diabetes on fetal cardiac tissue in experimental animal study model. Methods: Totally 12 female Wistar albino rats were divided into two groups, each consisting of 6 rats. Streptozotocin (60 mg/kg) was administered intraperitoneally to the study group by dissolving in citrate solution. The rats with a blood glucose level of 200 mg/dL and above were considered to be diabetic rats. Total antioxidant status (TAS), total oxidative stress (TOS) and oxidative stress index (OSI) values were calculated in the cardiac tissues and maternal serum samples of the fetuses delivered by cesarean section after the mating process. The cardiac tissues were also subjected to histopathological examination. Results: TOS and OSI values in fetal cardiac tissues of the diabetic rats were found to be significantly higher than that of the control group (p=0.026 and p=0.005). Histopathological examination revealed that the mitotic index was lower and the cell organization was found to be damaged in the fetuses of the study group rats. Conclusion: Increased levels of free oxygen radicals considered to be due to hyperglycemia may cause congenital anomalies, especially during organogenesis period, by disrupting cell homeostasis and adversely affecting mitosis.
https://ift.tt/2Ipl5TG
Impact of dexmedetomidine on hemodynamics in rabbits
Abstract Purpose: To evaluate the effects of single intravenous administration of Dexmedetomidine (DEX) on hemodynamics in rabbits. Methods: A total of 32 New Zealand white rabbits were randomly divided into the control group (Group C), Group D1 (2.75 μg/kg), Group D2 (5.5 μg/kg), and Group D3 (8.25 μg/kg) to compare systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), central venous pressure (CVP), left ventricular systolic pressure (LVSP), left ventricular end-stage diastolic pressure (LVEDP), left ventricular developmental pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax at different time points. Results: The levels of SBP, DBP, HR, LVSP, and LVEDP in Group D1, D2, and D3 were lower than that of Group C from T1 to T5 (P<0.05), but there was no significant difference at T6 and T7 (P>0.05). Compared with T0, the levels of SBP, DBP, HR, LVSP, LVEDP, and left arterial pressure (LAP) from T1 to T7 were decreased (P<0.05), but there was no significant difference in the other indexes (P>0.05). Conclusion: Dexmedetomidine can decrease blood pressure and heart rate in rabbits in a dose-dependent manner, but there is no effect on the myocardial systolic and diastolic function.
https://ift.tt/2rOBUfp
Action of a deproteinized xenogenic biomaterial in the process of bone repair in rats submitted to inhalation of cigarette smoke
Abstract Purpose: To investigate if the inorganic bovine bone matrix changes the bone formation in rats submitted to inhalation of cigarette smoke. Methods: Twenty Wistar rats were divided into two groups: Cigarette Clot Group (CCG), which in the inhalation chamber received the smoke of 10 cigarettes, 3 times a day, 10 minutes, for 30 days and had the surgical cavity filled by clot; Cigarette Biomaterial Group (CBG), submitted to the same inhalation technique but with the cavity filled by biomaterial. Results: In CCG there was a significant difference of new bone tissue in the analyzed periods (15 and 45 days), and in 15 days, there was 4.8 ± 0.42 of bone formed and 11.73 ± 0.59 (p <0.05) in 45 days. The CBG also showed a significant difference between the periods of 15 to 45 days, being respectively 6.16 ± 0.30 and 11.60 ± 0.61. However, when the groups were compared, within the same analyzed periods, a significant difference was observed only in the period of 15 days, with the new bone percentage being greater in the CBG. Conclusion: The bone matrix acted as an osteoinductive biomaterial, biocompatible and aided in the repair process, mainly in the initial period of recovery.
https://ift.tt/2L8uj4j
Comparison of platelet rich plasma versus fibrin glue on colonic anastomoses in rats
Abstract Purpose: To compare platelet rich plasma (PRP) and fibrin glue about the effect of anastomotic healing. Methods: Thirty six Wistar-Albino male rats diveded into 3 groups according to control(Group1), PRP (Group 2) and fibrin glue(Tisseel VH) (Group 3). The colon was transected with scissor and subsequently an end to end anastomosis was performed using continuous one layer 6/0 vicryl sutures. Postoperative 7th day effect of anastomotic healing measuring with tissue hydroxyproline(TH) level and anastomotic bursting pressure(ABP); moreover comparison of cytokine (IL-6 and IL-10) and procalcitonin levels on 1st,3rd and 7th days. Results: There was no statistically significant difference of the ABP and hydroxyproline levels between PRP and fibrin glue on the 7th day. There was no statistically significant difference between levels of proinflammatory cytokine (IL-6) (P=0.41), anti-inflammatory cytokine (IL-10) (P=0.35), and procalcitonin levels (P=0.63) on 1, 3 and 7 days. Conclusion: Fibrin glue and platelet rich plasma are shown to be effective in healing intestinal anastomoses without superior to each other.
https://ift.tt/2rOBF3Z
The protection effect and mechanism of hyperbaric oxygen therapy in rat brain with traumatic injury
Abstract Purpose: To investigate the effect of hyperbaric oxygen therapy (HBOT) on traumatic brain injury (TBI) outcome. Methods: The modified Marmarou's weight drop device was used to generate non-lethal moderate TBI rat model, and further developed in vitro astrocytes culturing system. Then, we analyzed the expression changes of interested genes and protein by quantitative PCR and western blot. Results: Multiple HBO treatments significantly reduced the expression of apoptosis promoting genes, such as c-fos, c-jun, Bax and weakened the activation of Caspase-3 in model rats. On the contrary, HBOT alleviated the decrease of anti-apoptosis gene Bcl-2 and promoted the expression of neurotrophic factors (NTFs), such as NGF, BDNF, GDNF and NT-3 in vivo. As a consequent, the neuropathogenesis was remarkably relied with HBOT. Astrocytes from TBI brain or those cultured with 21% O2 density expressed higher NTFs than that of corresponding controls, from sham brain and cultured with 7% O2, respectively. The NTFs expression was the highest in astrocytes form TBI brain and cultured with 21% O2, suggesting a synergistic effect existed between TBI and the following HBO treatment in astrocytes. Conclusion: Our findings provided evidence for the clinical usage of HBO treating brain damages.
https://ift.tt/2ImSDlh
Demineralized bone matrix and calcium-phosphate cement in bone regeneration in rats
Abstract Purpose: To compare bone regeneration in critical-sized defects in rat calvarium using demineralized bone matrix and calcium phosphate cement. Methods: Thirty Wistar rats were divided into 3 groups of 10 animals each. Two defects of 5-mm were made in the parietal bones of each animal. Group I had calcium phosphate cement placed in the experimental defect, Group II had filled with demineralized bone matrix and Group III had with the combination of the matrix and cement in equal parts. All animals had one defect left unfilled to serve as controls. Five animals in each group were sacrificed at 4 and 8 weeks. Histomorphometric analysis was used to quantify the amount of new bone within the defects. Results: The results showed that demineralized bone matrix-treated defects had significantly more new bone at 4 weeks compared to calcium phosphate cement-treated defects (p=0.03) and also had significantly more new bone at 8 weeks compared to unfilled defects (p=0.04). Conclusions: The demineralized bone matrix was superior to calcium phosphate cement in bone regeneration. It seems that calcium phosphate cement acted by inhibiting the osteogenesis when associated with a demineralized bone matrix and this combination should not be recommended.
https://ift.tt/2rNFOFp
Evaluation of prophylactic and therapeutic effects of sildenafil on acute radiation proctitis in rats
Abstract Purpose: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP). Methods: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis. Results: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group. While the prophylaxis group and the treatment group had significantly lower scores. High-dose group showed similar results as prophylaxis group. Histopathological findings of the prophylaxis group was more significant than the treatment group. Immunoreactivities of IL-1β, FGF-2, TNF- α and HIF-1α increased in the control group especially in the epithelial and cryptic regions. On the contrary, sildenafil application caused significant decreases of inflammatory markers in all treatment groups, specifically better results in the prophylaxis group. Conclusion: The sildenafil has anti-inflammatory effects on ARP, as well as protective effects against ARP and the protective effect of sildenafil surpasses its therapeutic effect histopathologically.
https://ift.tt/2L9okMO
Effect of melatonin on antioxidant capacity, ınflammation and apoptotic cell death in lung tissue of diabetic rats
Abstract Purpose: To investigate the effects of melatonin on antioxidant capacity, inflammation and apoptotic cell death (through expression of cleaved-caspase 3) in lung tissue samples of diabetic rats. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group) was made up of healthy rats. Group 2 (diabetes group) received streptozotocin at a dose of 50 mg/kg/day for 5 days.Group 3 (diabetes plus melatonin group) received streptozotocin at a dose of 50 mg/kg/day for 5 days and then they received melatonin at a dose of 20 mg/kg/day between 28thand 35thdays of the study. Results: Tissue MDA and MPO levels were found to be significantly higher in diabetes group compared to control group (p<0.05) whilst administration of melatonin was found to significantly lower this increase down to normal levels (p<0.05). Bronchus associated lymphoid tissue (BALT) was more severe in diabetics whereas administration of melatonin alleviated this hyperplasia. Cleaved caspase 3 activity was severe in hyperplastic BALT in diabetic rats however in lowered down to moderate level when melatonin was administered. Conclusion: The melatonin caused an increase in antioxidant capacity and decreased the expression of cleaved-caspase 3.
https://ift.tt/2rMQCnj
Vascular endothelial growth factor association with angiopoietin 1 promotes improvement in ventricular function after ischemic cardiomyopathy induced in mini pigs
Abstract Purpose: To investigate the safety and clinical, hemodynamic and tissue improvement ability in mini pigs undergoing cell and gene therapy for the treatment of acute myocardial infarction. Methods: Thirty-two mini pigs Br1 lineage, 12 months old, undergoing induction of acute myocardial infarction by occlusion of the diagonal branch of the paraconal coronary. They were divided into 4 groups: one control group and 3 treatment groups (cell therapy and gene cell therapy). Echocardiography reviews were performed on three occasions and histopathological analysis was performed after 4 weeks. Analysis of variance (ANOVA), Tukey and Wilcoxon tests, were performed. Results: Association of vascular endothelial growth factor (VEGF) with angiopoietin1 (Ang1) presented satisfactory results in the improvement of ventricular function following ischemic cardiomyopathy in mini pigs when compared to the results of the other treated groups. Conclusion: The therapy with VEGF and the combination of VEGF with Ang1, promoted recovered function of the myocardium, characterized by reduced akinetic area and induction of neovascularization.
https://ift.tt/2ImFl8o
Discrete linear canonical wavelet transform and its applications
The continuous generalized wavelet transform (GWT) which is regarded as a kind of time-linear canonical domain (LCD)-frequency representation has recently been proposed. Its constant-Q property can rectify the...
https://ift.tt/2wLaGfz
Sarcomatoid Carcinoma of Urinary Bladder: a Case Report
Abstract
Sarcomatoid carcinoma is an extremely rare aggressive tumor variant comprising about 0.3% of all primary tumors of the urinary bladder and carries an overall dismal prognosis. Diagnosis is important and is sometimes difficult. Immunohistochemistry plays an important role in establishing diagnosis. We report a case with sarcomatoid variant of bladder urothelial carcinoma and review the pathologic features. A 65-year-old male on evaluation of long standing obstructive voiding symptoms and intermittent hematuria found to have a bladder mass. Magnetic resonance urography revealed a 35 × 45 mm mass at dome of urinary bladder with perivesical fat infiltration. He underwent transurethral resection and histopathology revealed pT1 high-grade malignant spindle cell tumor. He underwent radical cystoprostatectomy with bilateral extended pelvic lymphadenectomy with EPLND with ileal conduit urine diversion. Histopathology revealed high-grade muscle invasive spindle cell tumor. The diagnosis was uncertain and two differential diagnosis were kept, sarcomatoid carcinoma and pleomorphic sarcoma. Finally, IHC confirmed the final diagnosis of sarcomatoid carcinoma as it was positive for cytokeratin, CK – 8/18, GATA 3. All lymph nodes were negative for metastasis (pT2, N0, Mx). Recognition of the rare variants of the urinary bladder urothelial tumors is imperative as it is affects the overall management and hence prognosis. Immunohistochemistry plays a paramount role in establishing the diagnosis.
https://ift.tt/2Iq2McQ
Determinants of Lactic Acidosis in Acute Cyanide Poisonings
Objectives: To investigate the magnitude of lactic acidosis in response to cyanide poisoning compared with the secondary response caused by cardiovascular shock. Design: Retrospective case-control observational study. Setting: University Hospital of Assistance Publique – Hôpitaux de Paris. Subjects: Patients admitted for suspicion of cyanide poisoning or drug overdose. Medical charts provided by Assistance Publique - Hôpitaux de Paris of patients between January 1988 and December 2015. Intervention: None. Measurements and Main Results: Twelve cyanide poisoned patients were matched to 48 controls by age, sex, systolic blood pressure, catecholamine administration, and outcome at discharge from ICU. Extracted data included age, sex, vital signs, symptoms, biochemical parameters, toxicological analysis, treatment, and outcome. Non-parametric tests were used. Multivariable analysis was used to adjust for confounders causing hyperlactacidemia. The median blood lactate concentration was significantly greater in the cyanide group (15.6 mmol/L) compared to the control group (4.1 mmol/L; p = 0.0003). Similarly, blood lactate concentration greater than or equal to 8 mmol/l was observed in 83% of the cyanide cases versus 27% of the matched controls. Multivariate analysis conferred hyperlactacidemia as the lone factor which significantly predicted cyanide poisoning at an odds of 73.0 (5.7-936.1). Moreover, blood cyanide level significantly correlated with the increase of blood lactate (p = 0.0033). Conclusions: This study supports the hypothesis lactic acidosis primarily results from the direct toxicity of cyanide.https://ift.tt/2IRASKa
Sedation Intensity in the First 48 Hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study*
Objectives: In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. Design: Harmonized data from prospective multicenter international longitudinal cohort studies Setting: Diverse mix of ICUs. Patients: Critically ill patients expected to be ventilated for longer than 24 hours. Interventions: Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively. Measurements and Main Results: Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and sensitivity analysis accounting for immortal time bias using the same variables within 120 and 168 hours. The main outcome was 180-day survival. We assessed 703 patients in 42 ICUs with a mean (SD) Acute Physiology and Chronic Health Evaluation II score of 22.2 (8.5) with 180-day mortality of 32.3% (227). The median (interquartile range) ventilation time was 4.54 days (2.47–8.43 d). Delirium occurred in 273 (38.8%) of patients. Sedation intensity, in an escalating dose-dependent relationship, independently predicted increased risk of death (hazard ratio [95% CI], 1.29 [1.15–1.46]; phttps://ift.tt/2k0KNza
Impact of Preadmission Opioid Treatment on 1-Year Mortality Following Nonsurgical Intensive Care*
Objectives: Compare all-cause mortality following nonsurgical ICU admission for opioid users with nonusers. Design: Nationwide register-based cohort study. Setting: All 43 ICUs in Denmark (7,028,668 citizens cumulatively during the study period). The Danish National Health Service provides universal healthcare, guaranteeing equal access to healthcare along with partial reimbursement for prescribed drugs. Patients: All 118,388 nonsurgical patients admitted to an ICU from 2005 to 2014. Intervention: Patients were categorized according to timing of last redeemed opioid prescription before admission: current user (prior 0–30 d), recent user (prior 31–365 d), former user (prior 365+ d), or nonuser (no prescription since 1994). Measurements: All-cause mortality 0–30 days and 31–365 days following ICU admission was calculated using the Kaplan-Meier method. Crude and adjusted hazard ratios with 95% CIs were computed using Cox regression, comparing users with nonusers. Adjusted models included age, gender, socioeconomic factors, comedications, and comorbidity. Main Results: Fifteen percent of the patients were current opioid users, 15% recent users, 30% former users, and 40% nonusers. Zero- to 30-day mortality was 35% for current users, 29% for recent users, 24% for former users, and 21% for nonusers. After confounder adjustment, current users remained at elevated risk during the first 30 days following ICU admission (hazard ratio, 1.20; 95% CI, 1.15–1.24). No association remained for recent or former users. A similar pattern was evident for 31–365-day all-cause mortality: 24% for current users, 19% for recent users, 13% for former users, and 10% for nonusers. During 31–365 days of follow-up, both current users and recent users remained at elevated risk of mortality after adjustment (hazard ratio, 1.47; 95% CI, 1.39–1.55 and hazard ratio, 1.20; 95% CI, 1.13–1.27, respectively). Conclusions: Current opioid users experience increased mortality during the first year following ICU admission.https://ift.tt/2wMtjj5
Interleukin-34 Ameliorates Survival and Bacterial Clearance in Polymicrobial Sepsis*
Objectives: Sepsis is a devastating condition with a high mortality rate and limited treatments. Sepsis is characterized by a failed host immune response to contain the infection, resulting in organ dysfunction. Interleukin-34 is new cytokine involved in infection and immunity. Whether interleukin-34 is beneficial or deleterious to sepsis and the underlying mechanisms remains unknown. Design: Prospective randomized animal investigation and in vitro studies. Setting: Research laboratory at a university hospital. Subjects: Wild-type C57BL/6 mice were used for in vivo studies, and septic human patients and healthy human subjects were used to obtain blood for in vitro studies. Interventions: Interleukin-34 concentrations were measured in human sepsis patients and healthy individuals. The effects of interleukin-34 administration on survival, bacterial burden, organ injury, and inflammatory response were assessed in a murine model of cecal ligation and puncture–induced polymicrobial sepsis. Measurements and Main Results: Interleukin-34 levels were significantly elevated in human sepsis and cecal ligation and puncture–induced experimental sepsis. Interleukin-34 administration improved survival and bacterial clearance, although suppressed vascular leakage and organ injury after cecal ligation and puncture–induced polymicrobial sepsis. Neutralization of interleukin-34 increased mortality rate and decreased bacterial clearance in septic mice. An increased neutrophil and macrophage influx were developed in interleukin-34–treated mice at the site of infection, accompanied by elevated production of neutrophil chemokine chemokine (C-X-C motif) ligand 1 and macrophage chemokine C-C motif chemokine ligand 2 in the peritoneal cavity. Depletion of neutrophils or macrophages reversed interleukin-34–mediated protection against polymicrobial sepsis. Conclusions: We reported for the first time a potential therapeutic role for interleukin-34 in sepsis and suggested that interleukin-34 is a novel target for the development of therapeutic agents against sepsis.https://ift.tt/2IRAxHo
Trends of Incidence and Risk Factors of Ventilator-Associated Pneumonia in Elderly Patients Admitted to French ICUs Between 2007 and 2014*
Objectives: To assess trends and risk factors of ventilator-associated pneumonia according to age, particularly in the elderly admitted to French ICUs between 2007 and 2014. Design: Multicenter, prospective French national Healthcare-Associated Infection surveillance network of ICUs ("Réseau REA-Raisin"). Settings: Two-hundred fifty six ICUs in 246 settings in France. Patients: Included were all adult patients hospitalized greater than or equal to 48 hours in ICUs participating in the network. Interventions: Ventilator-associated pneumonia surveillance over time. Measurements and Main Results: Overall and multidrug-resistant organism–related ventilator-associated pneumonia incidence rates were expressed per 1,000 intubation days at risk. Age was stratified into three groups: young (18–64 yr old), old (65–74 yr old), and very old (75+ yr old). Age-stratified multivariate mixed-effects Poisson regressions were undertaken to assess trends of ventilator-associated pneumonia incidence over time, with center as the random effect. Ventilator-associated pneumonia risk factors were also evaluated. Of 206,223 patients, 134,510 were intubated: 47.8% were young, 22.3% were old, and 29.9% were very old. Ventilator-associated pneumonia incidence was lower in the very old group compared with the young group (14.51; 95% CI, 16.95–17.70 vs 17.32; 95% CI, 16.95–17.70, respectively, phttps://ift.tt/2IFEqiT
Society of Critical Care Medicine Presidential Address−47th Annual Congress, February 2018, San Antonio, Texas
No abstract availablehttps://ift.tt/2IKBtxu
Racial Differences in Sepsis Mortality at U.S. Academic Medical Center–Affiliated Hospitals*
Objectives: To determine the racial disparities in severe sepsis hospitalizations and outcomes in U.S. academic medical center–affiliated hospitals. Design: Retrospective analysis of sepsis hospitalizations. Settings: U.S. academic medical center–affiliated hospitals participating in Vizient Consortium from 2012 to 2014. Patients: Sepsis hospitalizations using International Classification of Diseases, Ninth revision, discharge diagnoses codes defined by the Angus method. Interventions: None. Measurements and Main Results: We compared rates of sepsis hospitalization, ICU admission, organ dysfunction, and hospital mortality between blacks and whites. We repeated the analyses stratified by community-acquired, healthcare-associated, and hospital-acquired sepsis subtypes. Of 10,244,780 hospitalizations in our cohort, 1,114,386 (10.9%) had sepsis. Sepsis subtypes included community-acquired sepsis (61.8%), healthcare-associated sepsis (23.8%), and hospital-acquired sepsis (14.4%). Although the proportion of discharges with sepsis was lower for blacks than whites (106.72 vs 109.43 per 1,000 hospitalizations; phttps://ift.tt/2KwSZm7
Ultrasound-Guided Laryngeal Air Column Width Difference as a New Predictor for Postextubation Stridor in Children
Objectives: To assess the efficacy of ultrasound-guided laryngeal air column width difference in predicting postextubation stridor in children. Design: Prospective observational study. Setting: Single, tertiary care pediatric hospital. Patients: This study was carried out at PICU and surgical ICU, Tanta University Hospital on 400 ventilated children between January 2015 and May 2017. Patients who received mechanical ventilation and met criteria for a weaning trial were included. Intervention: Laryngeal ultrasound and cuff leak test. Measurements and Main Results: Ultrasound-guided laryngeal air column width and cuff leak test were measured before extubation. Laryngeal air column width is the width of air between the vocal cords seen by laryngeal ultrasonography. Laryngeal air column width difference is the width difference of air column passed through vocal cords with the balloon cuff inflated and deflated. Three-hundred fifty six patients (89%) had no postextubation stridor, whereas 44 patients (11%) developed postextubation stridor. Postextubation stridor was associated with younger age, less weight, female gender, prolonged duration of intubation, and ICU stay (phttps://ift.tt/2wP8eVq
An Exploratory Reanalysis of the Randomized Trial on Efficacy of Corticosteroids as Rescue Therapy for the Late Phase of Acute Respiratory Distress Syndrome*
Objectives: In the Acute Respiratory Distress Syndrome Network randomized controlled trial, methylprednisolone treatment was associated with increased return to mechanical ventilation with partial loss of early improvements. We hypothesize a causal relationship between protocol-driven rapid discontinuation of methylprednisolone post extubation and return to mechanical ventilation. To explore this possibility, we investigated the timing that events occurred in each treatment arm during active treatment intervention (efficacy) and after stopping therapy. Design and Settings: Retrospective intention-to-treat analysis of multicenter randomized controlled trial. Patients and Interventions: Patients were randomized to methylprednisolone (2 mg/kg/d) or placebo (89 vs 91). The target sample size was reduced post hoc and provided 80% power for an optimistic 50% mortality reduction. Measurements and Main Results: Findings are reported as methylprednisolone versus placebo. By day 28, fewer patients died before achieving extubation (15.7% vs 25.3% and risk ratio, 0.62; 95% CI, 0.34–1.13), more achieved successful extubation (71.9% vs 49.5% and risk ratio, 1.45; CI, 1.14–1.85), time to successful extubation was shorter (hazard ratio, 2.05; CI, 1.42–2.96), and more were discharged alive from the ICU (65.2% vs 48.3%; risk ratio, 1.35; CI, 1.04–1.75). After treatment discontinuation, more methylprednisolone-treated patients returned to mechanical ventilation (26.6% vs 6.7%; risk ratio, 3.98; CI, 1.24–12.79)—consistent with reconstituted systemic inflammation in the presence of adrenal suppression. Participants returning to mechanical ventilation without reinstitution of methylprednisolone had increased risk of ventilator dependence and mortality. Despite loss of early benefits, methylprednisolone was associated with sizable and significant improvements in all secondary outcomes and reduction in serious complications (shock and severe infections). Conclusions: During active intervention, methylprednisolone was safe and effective in achieving disease resolution. Our findings support rapid glucocorticoid discontinuation post extubation as likely cause of disease relapse. Gradual tapering might be necessary to preserve the significant improvements achieved during methylprednisolone administration.https://ift.tt/2IMJ8v3
RBC Transfusion Practice in Pediatric Extracorporeal Membrane Oxygenation Support
Objectives: To determine RBC transfusion practice and relationships between RBC transfusion volume and mortality in infants and children treated with extracorporeal membrane oxygenation. Design: Secondary analysis of a multicenter prospective observational study. Setting: Eight pediatric institutions within the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Collaborative Pediatric Critical Care Research Network. Patients: Patients age less than 19 years old treated with extracorporeal membrane oxygenation at a participating center. Interventions: None. Measurements and Main Results: Clinical data and target hemoglobin or hematocrit values (if set) were recorded daily by trained bedside extracorporeal membrane oxygenation specialists and research coordinators. Laboratory values, including hemoglobin and hematocrit, were recorded daily using the value obtained closest to 8:00 AM. RBC transfusion was recorded as total daily volume in mL/kg. Multivariable logistic regression was used to determine the relationship between RBC transfusion volume and hospital mortality, accounting for potential confounders. Average goal hematocrits varied across the cohort with a range of 27.5–41.3%. Overall, actual average daily hematocrit was 36.8%, and average RBC transfusion volume was 29.4 mL/kg/d (17.4–49.7 mL/kg/d) on extracorporeal membrane oxygenation. On multivariable analysis, each additional 10 mL/kg/d of RBC transfusion volume was independently associated with a 9% increase in odds of hospital mortality (adjusted odds ratio, 1.09 [1.02–1.16]; p = 0.009). Conclusions: In this multicenter cohort of pediatric extracorporeal membrane oxygenation patients, daily hematocrit levels were maintained at normal or near-normal values and RBC transfusion burden was high. RBC transfusion volume was independently associated with odds of mortality. Future clinical studies to identify optimum RBC transfusion thresholds for pediatric extracorporeal membrane oxygenation are urgently needed.https://ift.tt/2rHsdQX
Is Overall Mortality the Right Composite Endpoint in Clinical Trials of Acute Respiratory Distress Syndrome?*
Objectives: Overall mortality in patients with acute respiratory distress syndrome is a composite endpoint because it includes death from multiple causes. In most acute respiratory distress syndrome trials, it is unknown whether reported deaths are due to acute respiratory distress syndrome or the underlying disease, unrelated to the specific intervention tested. We investigated the causes of death after contracting acute respiratory distress syndrome in a large cohort. Design: A secondary analysis from three prospective, multicenter, observational studies. Setting: A network of multidisciplinary ICUs. Patients: We studied 778 patients with moderate-to-severe acute respiratory distress syndrome treated with lung-protective ventilation. Interventions: None. Measurements and Main Results: We examined death in the ICU from individual causes. Overall ICU mortality was 38.8% (95% CI, 35.4–42.3). Causes of acute respiratory distress syndrome modified the risk of death. Twenty-three percent of deaths occurred from refractory hypoxemia due to nonresolving acute respiratory distress syndrome. Most patients died from causes unrelated to acute respiratory distress syndrome: 48.7% of nonsurvivors died from multisystem organ failure, and cancer or brain injury was involved in 37.1% of deaths. When quantifying the true burden of acute respiratory distress syndrome outcome, we identified 506 patients (65.0%) with one or more exclusion criteria for enrollment into current interventional trials. Overall ICU mortality of the "trial cohort" (21.3%) was markedly lower than the parent cohort (relative risk, 0.55; 95% CI, 0.43–0.70; phttps://ift.tt/2KuI5x1
Survival and Safety Outcomes of ICU Patients Discharged Directly Home—A Direct From ICU Sent Home Study*
Objectives: Evaluate outcomes (mortality, morbidity, unplanned return visits) of patients who are discharged directly to home from the ICU. Design: Prospective cohort study. Setting: Two tertiary care medical-surgical-trauma ICUs at Canadian hospitals over 1 year (February 2016–2017). Subjects: All adult patients who were either discharged directly to home (Recruited and Nonrecruited cohorts) from ICU or discharged home within 24 hours after ward transfer (Ward Transfer cohort). Interventions: Direct discharge home from ICU or discharge home within 24 hours of ward transfer from ICU. Measurements and Main Results: One-hundred ninety-eight patients were in the study, 100 patients in the discharged directly to home Recruited arm, 37 patients in the discharged directly to home Nonrecruited arm, and 61 patients in the Ward cohort. All three patient cohorts had 0% mortality at 8 weeks post discharge. The unplanned return visit rate for the Recruited cohort was 24% (emergency department 18%, Ward 4%, ICU 1%), whereas the rate for the Nonrecruited cohort was 52% (emergency department 34%, Ward 14%, ICU 3%) and the Ward Transfer cohort was 46% (emergency department 17%, Ward 26%, ICU 3%) (p = 0.005). No home support was available for 7% of the discharged directly to home Recruited cohort. Twenty-four percent of patients had funded home care nursing, but the majority of patients (81%) relied on help from friends/family. Conclusions: Recruited discharged directly to home patients experienced very good 8-week postdischarge outcomes with 0% mortality and a low rate of ICU readmission (1%) or ward readmission (4%), but not an insignificant rate of emergency department visits (18%). Recruited discharged directly to home patients had better outcomes compared with nonrecruited discharged directly to home patients and patients transferred briefly to the ward prior to discharge home. Future work should include derivation of a clinical prediction tool to identify patient characteristics that make discharged directly to home safe and a randomized control trial to compare discharged directly to home with short stay ward transfers.https://ift.tt/2k0UVYF
Open Lung Biopsy in Nonresolving Acute Respiratory Distress Syndrome Commonly Identifies Corticosteroid-Sensitive Pathologies, Associated With Better Outcome*
Objectives: Approximately half of the patients undergoing lung biopsy for nonresolving acute respiratory distress syndrome exhibit another histologic pattern than diffuse alveolar damage, with some of the pathologies characterized by a potential response to corticosteroids. This study aimed to assess whether open lung biopsy performed in the ICU for nonresolving acute respiratory distress syndrome was able to identify steroid-sensitive diseases and whether patients with a steroid-sensitive pathology experienced different clinical courses and outcomes. Design: Retrospective analysis. Setting: One 22-bed mixed ICU within a tertiary medical center. Patients: Patients age greater than or equal to 16 years old who met the Berlin definition for acute respiratory distress syndrome and underwent open lung biopsy from January 2007 to January 2017. Interventions: None. Measurements and Main Results: During the study period, 695 patients diagnosed with acute respiratory distress syndrome were identified, 51 (7%) of whom underwent open lung biopsy. An alternative diagnosis to diffuse alveolar damage was found in 29 patients (57%), and a steroid-sensitive pathology was identified in 19 (37%). In-hospital and 180-day mortality rates were 55% and 61%, respectively. There was a significant difference in hospital mortality and 180-day mortality rates between patients with steroid-sensitive pathology and those with steroid-resistant pathology (37% vs 65%; phttps://ift.tt/2KrfsAX
Screening of melatonin, α-tocopherol, folic acid, acetyl-l-carnitine and resveratrol for anti-dengue 2 virus activity
Infections with the mosquito transmitted dengue virus (DENV) are a significant public health burden in many parts of the world. Despite the introduction of a commercial vaccine in some parts of the world, the ...
https://ift.tt/2IuLfAx
Prevalence and determinants of selected cardio-metabolic risk factors among people living with HIV/AIDS and receiving care in the South West Regional Hospitals of Cameroon: a cross-sectional study
Metabolic disorders and cardiovascular risk factors are not routinely assessed in the care of HIV patients in developing countries, known to have the highest disease burden. We described the prevalence and fac...
https://ift.tt/2k0JpMZ
Hypertension and its associated factors in Hosanna town, Southern Ethiopia: community based cross-sectional study
This study was conducted to determine the prevalence of hypertension and its associated factors among residents of Hosanna town in Hadiya Zone.
https://ift.tt/2Iqv5rD
Granulomatosis with polyangiitis: a 17 year experience from a tertiary care hospital in Pakistan
Granulomatosis with Polyangiitis (GPA) is an autoimmune, multi-system, small and medium vessel vasculitis with granulomatous inflammation. Aim of this study was to assess the clinical and radiological presenta...
https://ift.tt/2k1fTXp
Predictors of back disorder among Almeda textile factory workers, North Ethiopia
To guide the development of targeted interventions for the prevention of work-related back pain, this manuscript estimates the prevalence of back pain and its association with a variety of risk factors among A...
https://ift.tt/2IskRHs
Notch inhibition counteracts Paneth cell death in absence of caspase-8
Abstract
Opposing activities of Notch and Wnt signaling regulate mucosal barrier homeostasis and differentiation of intestinal epithelial cells. Specifically, Wnt activity is essential for differentiation of secretory cells including Wnt3-producing Paneth cells, whereas Notch signaling strongly promotes generation of absorptive cells. Loss of caspase-8 in intestinal epithelium (casp8∆int) is associated with fulminant epithelial necroptosis, severe Paneth cell death, secondary intestinal inflammation, and an increase in Notch activity. Here, we found that pharmacological Notch inhibition with dibenzazepine (DBZ) is able to essentially rescue the loss of Paneth cells, deescalate the inflammatory phenotype, and reduce intestinal permeability in casp8∆int mice. The secretory cell metaplasia in DBZ-treated casp8∆int animals is proliferative, indicating for Notch activities partially insensitive to gamma-secretase inhibition in a casp8∆int background. Our data suggest that casp8 acts in the intestinal Notch network.
https://ift.tt/2Im8ArT
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
