Religion and body weight: a review of quantitative studies

Summary

Increasing interest in relationships between religion and health has encouraged research about religion and body weight, which has produced mixed findings. We systematically searched 11 bibliographic databases for quantitative studies of religion and weight, locating and coding 85 studies. We conducted a systematic review, analysing descriptive characteristics of the studies as well as relevant religion-body weight associations related to study characteristics. We summarized findings for two categories of religion variables: religious affiliation and religiosity. For religious affiliation, we found evidence for significant associations with body weight in both cross-sectional and longitudinal studies. In particular, Seventh-Day Adventists had lower body weight than other denominations in cross-sectional analyses. For religiosity, significant associations occurred between greater religiosity and higher body weight in both cross-sectional and longitudinal studies. In particular, greater religiosity was significantly associated with higher body weight in bivariate analyses but less so in multivariate analyses. A greater proportion of studies that used a representative sample, longitudinal analyses, and samples with only men reported significant associations between religiosity and weight. Evidence in seven studies suggested that health behaviours and psychosocial factors mediate religion–weight relationships. More longitudinal studies and analyses of mediators are needed to provide stronger evidence and further elucidate religion–weight relationships.

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Injury and Liability Associated With Spine Surgery.

Background: Although spine surgery is associated with significant morbidity, the anesthesia liability profile for spine surgery is not known. We examined claims for spine procedures in the Anesthesia Closed Claims Project database to evaluate patterns of injury and liability. Materials and Methods: A retrospective cohort study was performed. Inclusion criteria were anesthesia claims provided for surgical procedures in 2000 to 2014. We compared mechanisms of injury for cervical spine to thoracic or lumbar spine procedures using [chi]2 and the Fisher exact test. Univariate and multivariate logistic regression analyses were used to determine factors associated with permanent disabling injury in spine surgery claims. Results: The 207 spine procedure (73% thoracic/lumbar; 27% cervical) claims comprised >10% of claims. Permanent disabling injuries to nerves, the spinal cord, and the eyes or visual pathways were more common with spine procedures than in nonspine procedures. Hemorrhage and positioning injuries were more common in thoracic/lumbar spine claims, whereas difficult intubation was more common in cervical spine claims. Multiple logistic regression demonstrated prone positioning (odds ratio=3.50; 95% confidence interval, 1.30-9.43) and surgical duration of >=4 hours increased the odds of severe permanent injury in spine claims (odds ratio=2.73; 95% confidence interval, 1.11-6.72). Conclusions: Anesthesia claims related to spine surgery were associated with severe permanent disability primarily from nerve and eye injuries. Prone positioning and surgical duration of >=4 hours were associated with permanent disabling injuries. Attention to positioning, resuscitation during blood loss, and reducing length of surgery may reduce these complications. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved

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Comparison of 3% Hypertonic Saline and 20% Mannitol for Reducing Intracranial Pressure in Patients Undergoing Supratentorial Brain Tumor Surgery: A Randomized, Double-blind Clinical Trial.

Background: In the present study, we hypothesized that 3% hypertonic saline (HS) is more effective than 20% mannitol to reduce intracranial pressure (ICP) and to modify brain bulk in patients undergoing an elective supratentorial craniotomy. Materials and Methods: After institutional review board approval, patients scheduled to undergo supratentorial craniotomy were enrolled into this prospective, randomized, double-blind study. The patients were monitored for routine hemodynamic parameters, depth of anesthesia, and ICP. They received 5 mL/kg 20% mannitol (n=20) or 3% HS (n=19) as infusion for 15 minutes. The patients' ICP values were monitored during hypertonic fluid infusion and throughout 30 minutes after infusion as a primary outcome. Secondary outcomes were hemodynamic variables, serum sodium value, blood gases, and surgeon brain relaxation assessment score (1=relaxed, 2=satisfactory, 3=firm, 4=bulging). In addition, the length of intensive care unit and hospital stay were recorded. Results: Demographic and tumor characteristics were similar between groups. The basal (before hypertonic infusion, ICPT0) and last (30 min after hypertonic infusion finished, ICPT45) ICP values were 13.7+/-3.0 and 9.5+/-1.9 mm Hg, respectively, for the M group, which were comparable with the corresponding levels of 14.2+/-2.8 and 8.7+/-1.1 mm Hg in the HS group (P>0.05). The median amount of ICP reduction between T0 and T45 timepoints were 4 (1 to 7) and 5 (1 to 9) mm Hg for group M and group HS, respectively (P=0.035). Baseline central venous pressure, pulse pressure variation, and serum sodium and lactate values were similar between groups, but the last measured pulse pressure variation and lactate value were lower, and sodium value was higher in group HS than in group M (P

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Endovascular Treatment of Acute Ischemic Stroke Under General Anesthesia: Predictors of Good Outcome.

Background: The choice of anesthetic technique, general anesthesia (GA) versus Monitored Anesthesia Care, may impact the outcome of patients undergoing endovascular treatment of acute ischemic stroke (AIS). The aim of this study was to identify the factors associated with good discharge outcome in patients receiving GA for AIS. Materials and Methods: Electronic medical records of patients above 18 years old who underwent endovascular treatment of AIS under GA at a Comprehensive Stroke Center from 2010 to 2014 were reviewed. Good outcome was defined as discharge modified Rankin Score 0 to 2 and poor outcome as modified Rankin Score 3 to 6; logistic regression analysis was performed to examine the association between the clinical characteristics and the outcome. Results: In total, 88 patients (56 males), aged 63+/-15 years with median National Institute of Health Stroke Scale (NIHSS) score 16 (range, 4 to 38) were included. Nineteen (22%) patients had good outcome and 78 (88%) had systolic blood pressure below the guideline recommended 140 mm Hg under GA. After adjusting for age and NIHSS score, the independent predictors of good discharge outcomes were higher maximum end-tidal carbon dioxide (odds ratio [OR], 1.14; confidence interval [CI], 1.02-1.28; P=0.02) and extubation after endovascular treatment (OR, 26.31; CI, 4.80-144.12; P

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Strontium release from Sr2+-loaded bone cements and dispersion in healthy and osteoporotic rat bone

Publication date: 28 September 2017
Source:Journal of Controlled Release, Volume 262
Author(s): Marcus Rohnke, Stefanie Pfitzenreuter, Boris Mogwitz, Anja Henß, Jürgen Thomas, Dina Bieberstein, Thomas Gemming, Svenja K. Otto, Seemun Ray, Matthias Schumacher, Michael Gelinsky, Volker Alt
Drug functionalization of biomaterials is a modern and popular approach in biomaterials research. Amongst others this concept is used for the functionalization of bone implants to locally stimulate the bone healing process. For example strontium ions (Sr²⁺) are administered in osteoporosis therapy to stimulate bone growth and have recently been integrated into bone cements. Based on results of different analytical experiments we developed a two-phase model for the transport of therapeutically active Sr²⁺-ions in bone in combination with Korsmeyer-Peppas kinetics for the Sr²⁺ release from bone cement. Data of cement dissolution experiments into water in combination with inductively coupled plasma mass spectrometry (ICP-MS) analysis account for dissolution kinetics following Noyes-Whitney rule. For dissolution in α-MEM cell culture media the process is kinetically hindered and can be described by Korsmeyer-Peppas kinetics. Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to determine the Sr²⁺ diffusion coefficient in healthy and osteoporotic trabecular rat bone. Therefore, bone sections were dipped in aqueous Sr²⁺-solution by one side and the Sr²⁺-profile was measured by classical SIMS depth profiling. The Sr²⁺ mobility can be described by a simple diffusion model and we obtained diffusion coefficients of (2.28±2.97)⋅10⁻¹²cm²/s for healthy and of (1.55±0.93)⋅10⁻¹⁰cm²/s for osteoporotic bone. This finding can be explained by a different bone nanostructure, which was observed by focused ion beam scanning electron microscopy (FIB-SEM) and transmission electron microscopy (TEM). Finally, the time and spatially resolved drug transport was calculated by finite element method for the femur of healthy and osteoporotic rats. The obtained results were compared to mass images that were obtained from sections of in vivo experiments by ToF-SIMS. The simulated data fits quite well to experimental results. The successfully applied model for the description of drug dispersion can help to reduce the number of animal experiments in the future.

Graphical abstract

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The role of prasugrel in the management of acute coronary syndromes: a systematic review

L'articolo The role of prasugrel in the management of acute coronary syndromes: a systematic review sembra essere il primo su European Review.

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An unusual neck tumor in a young pregnant woman: challenge diagnosis and response to treatment

Abstract

We report the case of a 19-year-old woman 33 weeks pregnant who presented a painful mass of progressive growth in the neck, having also dysphonia and dyspnea. Physical examination revealed a primary laryngeal tumor. A neuroendocrine small-cell carcinoma was diagnosed after histopathology, immunohistochemistry and genetic studies. Chemo-radiotherapy with a cisplatin-etoposide schedule was administered. Despite obtaining a complete response, the patient relapsed and finally survived 35 months with successive cisplatin-based treatments. Small-cell neuroendocrine carcinoma of the larynx is an uncommon entity, differential diagnosis can be problematic and treatment is challenging.

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Penile Mondor's disease in a patient treated with radical chemoradiation for anal cancer

Abstract

Penile Mondor's disease is a rare condition characterized by sclerosing thrombophlebitis of the superficial dorsal penile vein. Usually its causes are benign, but it is also evident in cancer patients. We report the case of a 62-year-old man with a cT4 anal cancer (infiltration of corpora spongiosa and penile bulb), associated with extensive loco-regional lymphadenopathy, who developed painful lumps in the midline of the anterior penile surface while receiving radical chemoradiotherapy. Physical examination revealed two palpable cord-like swellings located 2 cm from the pubic symphysis. Color Doppler ultrasound established the diagnosis of Mondor's disease. The patient was successfully managed with non-steroidal anti-inflammatory drugs. The causative factors were pelvic malignancy and radiotherapy. The diagnosis was challenging since Mondor's disease is a rare condition and the differential diagnosis included malignancy progression. This is the first case report describing penile Mondor's disease in a patient with anal cancer under chemoradiotherapy.

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Huge teratoma in a teenager

Abstract

Mature cystic teratoma is the most common ovarian tumor in young females. We are presenting a 13-year-old African–American female with abdominal distension. Computed tomography of the abdomen showed midline cystic mass. Diagnosis was confirmed after laparoscopic left salpingo-oophorectomy. Malignant transformation of mature cystic teratoma is rare.

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Increased α5β1 integrin could improve tumour cell-killing performance in geriatric patients

A new report in the Journal of Leukocyte Biology describes an important step toward developing cancer treatments involving the body's immune system. Specifically, chimeric antigen receptor T cell (CAR-T) therapy involves collecting white blood cells from...

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Shock Mechanism Analysis and Simulation of High-Power Hydraulic Shock Wave Simulator

The simulation of regular shock wave (e.g., half-sine) can be achieved by the traditional rubber shock simulator, but the practical high-power shock wave characterized by steep prepeak and gentle postpeak is hard to be realized by the same. To tackle this disadvantage, a novel high-power hydraulic shock wave simulator based on the live firing muzzle shock principle was proposed in the current work. The influence of the typical shock characteristic parameters on the shock force wave was investigated via both theoretical deduction and software simulation. According to the obtained data compared with the results, in fact, it can be concluded that the developed hydraulic shock wave simulator can be applied to simulate the real condition of the shocking system. Further, the similarity evaluation of shock wave simulation was achieved based on the curvature distance, and the results stated that the simulation method was reasonable and the structural optimization based on software simulation is also beneficial to the increase of efficiency. Finally, the combination of theoretical analysis and simulation for the development of artillery recoil tester is a comprehensive approach in the design and structure optimization of the recoil system.

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Intercostal Artery Laceration: Rare Complication of Thoracentesis and Role of Ultrasound in Early Detection

Hemothorax is a rare but potentially fatal postthoracentesis complication. Early clinical signs may be nonspecific resulting in diagnostic delay. A high index of suspicion is vital for early diagnosis and intervention to avoid further bleeding. Following procedure, early bedside ultrasound findings can be vital for early detection. We report a case of massive hemothorax in a 63-year-old male following therapeutic thoracentesis. Diagnosis was made following highly suggestive sonographic findings prompting thoracotomy and lacerated intercostal artery cauterization.

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The Reliability and Validity of Using Ice to Measure Cold Pain Threshold

Cold pain threshold (CPT) measures an individual's pain threshold in response to a cold stimulus. CPT is most accurately determined with specialised equipment; however this technology is not readily accessible to clinicians. Instead, ice has been employed to measure CPT. An optimal ice protocol has not yet been identified. The aim of this study was to evaluate the reliability and validity of two CPT protocols using ice in a young, healthy population. Twenty-two participants aged 22.6 (SD 1.81) years underwent CPT measurements over 6 anatomical sites across 3 protocols, which were repeated in 2 sessions. One protocol measured pain (PVAS) following ice applied for a standardised period of 30 seconds; a second protocol measured time to onset of pain, and the reference standard measured CPT using laboratory equipment (TSA-II). The PVAS protocol demonstrated the best reliability (mean ICC 0.783, 95% CI 0.706 to 0.841), but the Timed protocol demonstrated superior validity compared to the reference standard (mean ICC −0.504, 95% CI −0.621 to −0.365).

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IL-10-Producing B Cells Suppress Effector T Cells Activation and Promote Regulatory T Cells in Crystalline Silica-Induced Inflammatory Response In Vitro

Long-term exposure to crystalline silica leads to silicosis, which is characterized by persistent lung inflammation and lung fibrosis. Multiple immune cells have been demonstrated to participate in crystalline silica-induced immune responses. Our previous study indicated that B10 could control lung inflammation through modulating the Th balance in experimental silicosis in mice. However, the regulatory mechanism of B10 on CD4+ T cells is still unclear. MACS-sorted CD19+ B cells from the three different groups were cultured with CD4+ T cells either with or without transwell insert plates to evaluate the effects of B10 on CD4+ T cells, including Teff and Treg. B10 was eliminated by anti-CD22 application in vivo. Flow cytometry was used to test the frequencies of CD4+ T cells, and the expressions of the related cytokines were detected by real-time PCR and CBA. Insufficient B10 elevated the levels of proinflammatory cytokines and promoted Th responses in a way independent upon cell-cell contact in the Teff and B cell coculture system. B10 could both increase Treg activity and enhance conversion of Teff into Treg. Our findings demonstrated that B10 could affect Th responses by the release of IL-10, enhancing Treg functions and converting Teff into Treg.

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Intrathecal Resiniferatoxin Modulates TRPV1 in DRG Neurons and Reduces TNF-Induced Pain-Related Behavior

Transient receptor potential vanilloid-1 (TRPV1) is a nonselective cation channel, predominantly expressed in sensory neurons. TRPV1 is known to play an important role in the pathogenesis of inflammatory and neuropathic pain states. Previous studies suggest interactions between tumor necrosis factor- (TNF-) alpha and TRPV1, resulting in a modulation of ion channel function and protein expression in sensory neurons. We examined the effect of intrathecal administration of the ultrapotent TRPV1 agonist resiniferatoxin (RTX) on TNF-induced pain-associated behavior of rats using von Frey and hot plate behavioral testing. Intrathecal injection of TNF induces mechanical allodynia (2 and 20 ng/kg) and thermal hyperalgesia (200 ng) 24 h after administration. The additional intrathecal administration of RTX (1.9 μg/kg) alleviates TNF-induced mechanical allodynia and thermal hyperalgesia 24 h after injection. In addition, TNF increases the TRPV1 protein level and number of TRPV1-expressing neurons. Both effects could be abolished by the administration of RTX. These results suggest that the involvement of TRPV1 in TNF-induced pain offers new TRPV1-based experimental therapeutic approaches and demonstrates the analgesic potential of RTX in inflammatory pain diseases.

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AQUACEL® Ag Surgical Dressing Reduces Surgical Site Infection and Improves Patient Satisfaction in Minimally Invasive Total Knee Arthroplasty: A Prospective, Randomized, Controlled Study

The use of modern surgical dressings to prevent wound complications and surgical site infection (SSI) after minimally invasive total knee arthroplasty (MIS-TKA) is lacking. In a prospective, randomized, controlled study, 240 patients were randomized to receive either AQUACEL Ag Surgical dressing (study group) or a standard dressing (control group) after MIS-TKA. The primary outcome was wound complication (SSI and blister). The secondary outcomes were wear time and number of dressing changes in the hospital and patient satisfaction (pain, comfort, and ease of use). In the intention-to-treat analysis, there was a significant reduction in the incidence of superficial SSI (0.8%, 95% CI 0.00–2.48) in the study group compared to 8.3% (95% CI 3.32–13.3) in the control group (). There were no differences in blister and deep/organ-space SSIs between the two groups. Multivariate analysis revealed that AQUACEL Ag Surgical dressing was an independent risk factor for reduction of SSI (odds ratio: 0.07, 95% CI: 0.01–0.58, ). The study group had longer wear time ( versus days, ) and lower number of dressing changes ( versus times, ). Increased patient satisfaction () was also noted in the study group. AQUACEL Ag Surgical dressing is an ideal dressing to provide wound care efficacy, patient satisfaction, reduction of SSI, and cost-effectiveness following MIS-TKA.

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Adaptive Geometry Images for Remeshing

Geometry images are a kind of completely regular remeshing methods for mesh representation. Traditional geometry images have difficulties in achieving optimal reconstruction errors and preserving manually selected geometric details, due to the limitations of parametrization methods. To solve two issues, we propose two adaptive geometry images for remeshing triangular meshes. The first scheme produces geometry images with the minimum Hausdorff error by finding the optimization direction for sampling points based on the Hausdorff distance between the original mesh and the reconstructed mesh. The second scheme produces geometry images with higher reconstruction precision over the manually selected region-of-interest of the input mesh, by increasing the number of sampling points over the region-of-interest. Experimental results show that both schemes give promising results compared with traditional parametrization-based geometry images.

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Arthroscopically Assisted Coracoclavicular Fixation Using a Single Flip Button Device Technique: What Are the Main Factors Affecting the Maintenance of Reduction?

Background. Among coracoclavicular (CC) fixation techniques, the use of flip button device was demonstrated to have successful outcomes with the advantage of being able to accommodate an arthroscopic procedure. Purpose. This study was conducted to investigate the factors associated with loss of fixation after arthroscopically assisted CC fixation using a single flip button device for acromioclavicular (AC) joint dislocations. Materials and Methods. We enrolled a total of 47 patients (35 men and 12 women). Plain radiography was performed at a mean of 24 months postoperatively to evaluate the final radiological outcome. The primary outcome measure was a long-term reduction of the AC joint for at least 24 months. Results. We found that 29 patients had a high quality reduction (61.7%) and 18 patients had a low quality reduction (38.3%) in initial postoperative CT findings. Our study showed that the duration (5 days) from injury to treatment and the quality of initial postoperative reduction were significantly associated with the maintenance of reduction at final follow-up. Conclusion. Our study showed that maintaining stable reduction after arthroscopically assisted CC fixation using a single flip button device technique is difficult especially in patients who received delayed treatment or whose initial reduction quality was poor.

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Recurrent urinary tract infections and low secretory IgA following CD19-directed CAR T-cell therapy for relapsed acute lymphoblastic leukemia

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Variations in pediatric emergency medicine physician practices for intravenous fluid management in children with sickle cell disease and vaso-occlusive pain: A single institution experience

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Prevalence of multi-drug resistant organisms in stool of paediatric patients with acute leukaemia and correlation with blood culture positivity: A single institution experience

Abstract

Background

Multi-drug resistant (MDR) bacteria are associated with increased morbidity and mortality in children with acute leukaemia. The present study was conducted to assess the prevalence of MDR bacteria in stool cultures of patients with acute leukaemia at presentation to the hospital. The results were then correlated with blood cultures when patients developed septicaemia.

Patients and methods

The study involved analysis of case records of patients with newly diagnosed acute leukaemia less than 18 years of age treated at our centre from January 2015 to December 2015. Stool cultures were sent within 72 hr of hospital admission and blood cultures were sent when clinically indicated. MDR was defined as resistance to at least one antibiotic in three or more following antimicrobial groups: cephalosporins, β-lactam/β-lactamase inhibitor, carbapenems, fluoroquinolones and aminoglycosides.

Results

The analysis included 85 patients with acute leukaemia, among whom 48 of 85 (56%) patients had positive stool cultures and 42 of 85 (50%) patients were positive for MDR bacteria. Blood cultures were positive in 13 of 48 patients (27%, seven MDR and six non-MDR) with positive stool cultures and three of 37 patients (8%, one MDR and two non-MDR) with negative stool cultures (P = 0.01). The concordance between stool and blood culture for similar organism was 61%. There were seven deaths in 48 stool culture positive patients and two deaths in 37 stool culture negative patients.

Conclusion

This study shows the high prevalence of MDR bacteria in newly diagnosed children with acute leukaemia. Colonisation with MDR bacteria in stools is associated with increased positivity of blood cultures and mortality.

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Folate deficiency in north Indian children undergoing maintenance chemotherapy for acute lymphoblastic leukemia—Implications and outcome

Abstract

Background

Treatment-related toxicity and mortality are not uncommon during maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL), especially in the low- and middle-income countries (LMIC). Undernutrition and micronutrient deficiencies are commonly seen in children from LMICs undergoing treatment for ALL. The present study examines the prevalence and clinical implications of folate deficiency in north Indian children with ALL during the maintenance phase of treatment in view of prolonged antifolate treatment and high population prevalence of folate deficiency.

Procedures

Pre-cycle folate levels/deficiency as well as weight for age z-score and serum albumin level were determined and correlated with complications of treatment and mortality encountered during the maintenance phase of treatment.

Results

Twenty-nine of 52 children enrolled in the study had folate deficiency at some point during maintenance chemotherapy. Neutropenia (18 of 29 vs. 4 of 23; P = 0.002), thrombocytopenia (17 of 29 vs. 4 of 23; P = 0.005), febrile neutropenia (17 of 29 vs. 4 of 23; P = 0.005), and need for chemotherapy dose reduction (20 of 29 vs. 7 of 21; P = 0.01) were more common in folate-deficient children. Maintenance deaths were higher (8 of 29 vs. 1 of 23; P = 0.03) and survival lower (P = 0.02) in deficient children. In multivariate analysis, hypoalbuminemia (P = 0.02) and folate deficiency (P = 0.01) were associated with febrile neutropenia, and folate deficiency with maintenance deaths (P = 0.03).

Conclusions

Folate deficiency was associated with treatment-related complications and adverse outcome in our patients. The risks and benefits of folate supplementation in deficient children during maintenance chemotherapy need to be explored with properly designed randomized studies in similar settings.

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Value of flow cytometric analysis of peripheral blood samples in children diagnosed with acute lymphoblastic leukemia

Abstract

Diagnostic procedures in children with acute lymphoblastic leukemia (ALL) are typically performed under general anesthesia. Anticipation of the diagnosis based on findings in peripheral blood allows scheduling of the first dose of intrathecal chemotherapy and diagnostic bone marrow (BM) aspirate during a single anesthetic. We retrospectively compared paired results of peripheral blood (PB) flow cytometric analysis and BM evaluation in 383 children with ALL diagnosed consecutively at a single center and found very high concordance of results between both tests. We conclude that PB flow cytometry may help streamline planning of procedure-related anesthetics during diagnosis and early treatment of childhood ALL.

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A cost analysis of individualized asparaginase treatment in pediatric acute lymphoblastic leukemia

Abstract

Background

Therapeutic drug monitoring (TDM) of asparaginase is necessary to respond to variability in asparaginase activity levels, detect silent inactivation, and distinguish between real allergies and allergic-like reactions with and without asparaginase neutralization, respectively. In this study, the costs of an individualized and fixed asparaginase dosing schedule were compared.

Procedure

Patients, treated according to the Dutch Childhood Oncology Group ALL-11 protocol (individualized PEGasparaginase treatment, starting dose: 1,500 IU/m²) or ALL-10 protocol (native Escherichia coli asparaginase followed by 2,500 IU/m² PEGasparaginase), were included. To focus on TDM of PEGasparaginase, the costs were also calculated excluding patients treated with Erwinia asparaginase and compared to a hypothetical protocol with a fixed dose of 1,500 IU/m² PEGasparaginase. Direct asparaginase-related medical costs, including costs for asparaginase use (calculated with the absolute dose), TDM, laboratory tests, daycare treatment, and outpatient clinic visits, were calculated.

Results

Eighty-three ALL-10 patients and 51 ALL-11 patients were included. The asparaginase-related costs were 30.8% lower in ALL-11 than in ALL-10 ($29,048 vs. $41,960). The ALL-11 costs of nonallergic patients were 20.4% lower, when using TDM, than the hypothetical protocol with a fixed dose of 1,500 IU/m² ($13,178 vs. $16,551). TDM accounted for 12.4% of the costs. Including asparaginase waste, TDM in ALL-11 will be cost saving if three doses can be prepared out of one vial compared to a fixed dose of 1,500 IU/m².

Conclusions

TDM of asparaginase is cost saving if calculated with the absolute asparaginase dose and will be if the waste is minimalized by preparing multiple doses out of one vial.

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High birth prevalence of sickle cell disease in Northwestern Tanzania

Abstract

Background

Worldwide, hemoglobinopathies affect millions of children. Identification of hemoglobin disorders in most sub-Saharan African countries is delayed until clinical signs of the disease are present. Limited studies have been conducted to understand their prevalence and clinical presentation among newborns in resource-limited settings.

Methodology

This was a prospective cohort study. Newborns (aged 0–7 days) at two hospitals in Northwestern Tanzania were enrolled and followed prospectively for 6 months. Clinical and laboratory information were collected at baseline. Participants were screened for hemoglobinopathies using high-performance liquid chromatography. Clinical and laboratory follow-up was performed at 3 and 6 months for those with hemoglobinopathies as well as a comparison group of participants without hemoglobinopathies.

Results

A total of 919 newborns were enrolled. Among these, 1.4% (13/919) had sickle cell anemia or Hb S/β⁰-thalassemia (Hb FS), and 19.7% (181/919) had sickle cell trait or Hb S/β⁺ thalassemia (Hb FAS). Furthermore, 0.2% (two of 919) had β⁺-thalassemia. Red cell indices compared between Hb FS, Hb FAS, and Hb FA were similar at baseline, but hemoglobin was lower and red cell distribution width was higher in children with Hb FS at 3- and 6-month follow-up. Febrile episodes were more common for children with Hb FS at 3- and 6-month follow-up.

Conclusion

The prevalence of sickle cell disease among neonates born in Northwestern Tanzania is one of the highest in the world. Newborn screening is needed early in life to identify neonates with hemoglobinopathies so that clinical management may commence and morbidity and mortality related to hemoglobinopathies be reduced.

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Transfusion-transmitted babesiosis leading to severe hemolysis in two patients with sickle cell anemia

Abstract

The intracellular parasites Babesia microti and Babesia duncani can be transmitted by blood transfusion and cause severe life-threatening hemolytic anemia in high-risk patients, including those with sickle cell disease. The rarity of the diagnosis, as well as its similar clinical presentation to delayed hemolytic transfusion reaction, may lead to a delay in diagnosis, as well as inappropriate treatment with steroids or other immunosuppressive agents. The morbidity caused by this disease in especially vulnerable populations justifies the need for a universal blood-screening program in endemic areas.

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How to optimize dose in hybrid operating rooms

A clinical team from Liverpool, U.K., has revealed a 14-point strategy for...

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A cross sectional study of the relationship between the exposure of pregnant women to military attacks in 2014 in Gaza and the load of heavy metal contaminants in the hair of mothers and newborns

Objective

Metal contamination of humans in war areas has rarely been investigated. Weaponry's heavy metals become environmentally stable war remnants and accumulate in living things. They also pose health risks in terms of prenatal intake, with potential long term risks for reproductive and children's health. We studied the contribution of military attacks to the load of 23 metals in the hair of Palestinian women in the Gaza Strip, who were pregnant at the time of the military attacks in 2014, and their newborns. We compared the metal load in the mothers with values for adult hair from outside the war area (RHS) as the reference. We investigated heavy metals trans-passing in utero, and assessed if the heavy metal intake could derive from sources unrelated to the war.

Design

Cross sectional study.

Participants and setting

Cross sectional convenience sample of 502 mothers delivering in the Gaza Strip and their newborns.

Main outcome measured

Measure of the load of heavy metals in mother and newborn hair by inductively coupled plasma-mass spectrometry (ICP-MS). Comparison of metal loads with the reference RHS, between groups with different exposures to attacks and house/agriculture chemicals, and between mothers and newborns. Data for birth registry and for exposures to war and other known risk factors were obtained at interview with the mothers. Photographic documentation of damage from military attacks was obtained.

Results

The whole cross sectional convenience sample had a significantly higher load of heavy metals than the reference RHS. Women exposed to military attacks had a significantly higher load of heavy metals than those not exposed; the load in newborns correlated positively with the mothers' load. No significant difference was found between users/non-users of house/agriculture chemicals. No other known confounder was identified.

Conclusions

High heavy metal loads in mothers, reflected in those of their newborns, were associated with exposure to military attacks, posing a risk of immediate and long term negative outcomes for pregnancy and child health. Surveillance, biomonitoring and further research are recommended. Implications for general and public health are discussed.

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Validation of Digital Pathology for Primary Histopathological Diagnosis of Routine, Inflammatory Dermatopathology Cases.

Background: Digital pathology (DP) systems have been validated for routine, histopathological diagnosis by several investigators. The diagnostic matter in previous studies is composed mostly of neoplasms. However, in dermatopathology, inflammatory diseases constitute a greater proportion of cases and have been under-represented in this literature. Herein, we report the results of a prospective, DP side-by-side validation study comparing the histologic assessment of routine, clinical inflammatory dermatopathology cases by whole slide imaging (WSI) and traditional light microscopy (LM). Methods: Glass slides were digitized at x40 magnification. Two dermatopathologists rendered diagnoses digitally and immediately thereafter by light microscopy. Additional recuts, special, and immunohistochemical stains obtained during workup were scanned and evaluated similarly. Morphological features used to make diagnoses and appreciable differences in histology were recorded. Results: A total of 332 slides representing 93 cases were examined, including 157 hematoxylin & eosin sections, 132 special stains, and 43 immunohistochemical slides. In total, 333 microscopic features important for rendering inflammatory diagnoses were identified. Two discrepant instances were noted wherein Gram-positive cocci were identified using traditional microscopy but not by DP (x40 scan). Eosinophils, melanin granules, and mucin were identified on both modalities but were noted to have different appearances. Conclusions: Our findings indicate that DP is sufficient for primary diagnosis in inflammatory dermatopathology. Higher magnification scanning may be required to identify submicron features, such as microorganisms. Subtle differences in image quality between these 2 modalities may contribute to varied histologic interpretations of which pathologists should be aware when validating clinical DP systems. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Metastatic Cutaneous Paraganglioma: A Case Report and Review of the Literature.

Paragangliomas are rare neoplasms that arise from chromaffin cells of the sympathetic and parasympathetic nervous system. These tumors are often cured by surgical resection but the risk for metastatic disease exists, particularly for extra-adrenal paragangliomas. The behavior of these tumors is unpredictable, and clinical and histopathological features associated with malignancy have not been determined. The most common sites of metastases include local and distant lymph nodes, bone, liver, and lung. Cutaneous metastases are exceedingly rare with only 2 reported cases, both of which presented on the scalp. Here we describe a 78-year-old woman with cutaneous metastatic paraganglioma presenting as a forehead nodule, which developed 15 years after her initial diagnosis of paraganglioma. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Bullous Erythema Nodosum Leprosum as the First Manifestation of Multibacillary Leprosy: A Rare Phenomenon.

Erythema nodosum leprosum (ENL) may uncommonly present before treatment in patients with multibacillary leprosy. Atypical manifestations are known in ENL and may be clinically misleading. Such wide variations in the clinical presentation of leprosy in reaction make histopathology an important tool for supporting clinical diagnosis. We report bullous ENL presenting as the first manifestation of leprosy in a 30-year-old Indian man diagnosed using histopathology. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Genetic-Metabolic Coupling for Targeted Metabolic Engineering

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Stefano Cardinale, Felipe Gonzalo Tueros, Morten Otto Alexander Sommer
Production of chemicals in microbes often employs potent biosynthetic enzymes, which can interact with the microbial native metabolism to affect cell fitness and product yield. However, production optimization largely relies on data collected from wild-type strains in the absence of metabolic perturbations, thus limiting their relevance to specific conditions. Here, we address this issue by coupling cell fitness to the production of thiamine diphosphate in Escherichia coli using a synthetic RNA biosensor. We use this strategy to interrogate a library of transposon mutants and elucidate the native gene network influencing both cell fitness and thiamine production. Ultimately, we identify effectors of the OxyR-Fur stress response that limit thiamine biosynthesis via alternative regulation of iron storage and Fe-S cluster inclusion in enzymes. This study presents a new approach for the reliable high-throughput identification of genetic targets of both known and unknown function that are directly relevant to a specific biosynthetic process.

Graphical abstract

Teaser

Cardinale et al. investigate the specific impact on the cell of synthetic metabolic pathways. By linking the growth of bar-coded mutants with end-product biosensing in E. coli, the authors identify genetic targets in the cellular Fe-S cluster biosynthesis specifically affecting the production of recombinant thiamine.


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Intrinsic Autophagy Is Required for the Maintenance of Intestinal Stem Cells and for Irradiation-Induced Intestinal Regeneration

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Jumpei Asano, Taku Sato, Shizuko Ichinose, Mihoko Kajita, Nobuyuki Onai, Shigeomi Shimizu, Toshiaki Ohteki
Autophagy is a lysosomal degradation pathway with important roles in physiological homeostasis and disease. However, the role of autophagy in intestinal stem cells (ISCs) is unclear. Here, we show that intrinsic autophagy in ISCs is important for ISC homeostasis. Mice lacking autophagy protein 5 (ATG5) in intestinal epithelial cells (iECs) (Villin-Cre: Atg5^fl/fl, hereafter Atg5^ΔIEC mice) or in all iECs except Paneth cells (Ah-Cre: Atg5^fl/fl mice) had significantly fewer ISCs than did control mice and showed impaired ISC-dependent intestinal recovery after irradiation. Crypt ISCs from Atg5^ΔIEC mice had significantly higher reactive oxygen species (ROS) levels than did those from control mice. A ROS-inducing reagent decreased the ISC number and impaired ISC regenerative capacity ex vivo, and treating Atg5^ΔIEC mice with an antioxidant rescued their defects. Our results show that intrinsic autophagy supports ISC maintenance by reducing excessive ROS. Optimizing autophagy may lead to autophagy-based therapies for intestinal injuries.

Graphical abstract

Teaser

Autophagy is a lysosomal degradation pathway with important roles in physiological homeostasis and disease. Asano et al. find that intrinsic autophagy is important for the maintenance of intestinal stem cells by reducing excessive reactive oxygen species. This stem cell maintenance is necessary to provide damage-induced intestinal regeneration.


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Time-Restricted Feeding Shifts the Skin Circadian Clock and Alters UVB-Induced DNA Damage

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Hong Wang, Elyse van Spyk, Qiang Liu, Mikhail Geyfman, Michael L. Salmans, Vivek Kumar, Alexander Ihler, Ning Li, Joseph S. Takahashi, Bogi Andersen
The epidermis is a highly regenerative barrier protecting organisms from environmental insults, including UV radiation, the main cause of skin cancer and skin aging. Here, we show that time-restricted feeding (RF) shifts the phase and alters the amplitude of the skin circadian clock and affects the expression of approximately 10% of the skin transcriptome. Furthermore, a large number of skin-expressed genes are acutely regulated by food intake. Although the circadian clock is required for daily rhythms in DNA synthesis in epidermal progenitor cells, RF-induced shifts in clock phase do not alter the phase of DNA synthesis. However, RF alters both diurnal sensitivity to UVB-induced DNA damage and expression of the key DNA repair gene, Xpa. Together, our findings indicate regulation of skin function by time of feeding and emphasize a link between circadian rhythm, food intake, and skin health.

Graphical abstract

Teaser

Little is known about the effect of time of feeding on skin function. Wang et al. find that time-restricted feeding schedules affect skin gene expression, epidermal progenitor cell proliferation, and UVB-induced DNA damage, pointing to a modulatory role for food-intake timing in skin biology.


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Blockage of Core Fucosylation Reduces Cell-Surface Expression of PD-1 and Promotes Anti-tumor Immune Responses of T Cells

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Masahiro Okada, Shunsuke Chikuma, Taisuke Kondo, Sana Hibino, Hiroaki Machiyama, Tadashi Yokosuka, Miyako Nakano, Akihiko Yoshimura
Programmed cell death 1 (PD-1) is highly expressed on exhausted T cells and inhibits T cell activation. Antibodies that block the interaction between PD-1 and its ligand prevent this inhibitory signal and reverse T cell dysfunction, providing beneficial anti-tumor responses in a substantial number of patients. Mechanisms for the induction and maintenance of high PD-1 expression on exhausted T cells have not been fully understood. Utilizing a genome-wide loss-of-function screening method based on the CRISPR-Cas9 system, we identified genes involved in the core fucosylation pathway as positive regulators of cell-surface PD-1 expression. Inhibition of Fut8, a core fucosyltransferase, by genetic ablation or pharmacologic inhibition reduced cell-surface expression of PD-1 and enhanced T cell activation, leading to more efficient tumor eradication. Taken together, our findings suggest that blocking core fucosylation of PD-1 can be a promising strategy for improving anti-tumor immune responses.

Graphical abstract

Teaser

Using a genome-wide loss-of-function screening method, Okada et al. identify genes involved in the core fucosylation pathway as positive regulators of cell-surface PD-1 expression.


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A Conserved Splicing Silencer Dynamically Regulates O-GlcNAc Transferase Intron Retention and O-GlcNAc Homeostasis

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Sung-Kyun Park, Xiaorong Zhou, Kathryn E. Pendleton, Olga V. Hunter, Jennifer J. Kohler, Kathryn A. O'Donnell, Nicholas K. Conrad
Modification of nucleocytoplasmic proteins with O-GlcNAc regulates a wide variety of cellular processes and has been linked to human diseases. The enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) add and remove O-GlcNAc, but the mechanisms regulating their expression remain unclear. Here, we demonstrate that retention of the fourth intron of OGT is regulated in response to O-GlcNAc levels. We further define a conserved intronic splicing silencer (ISS) that is necessary for OGT intron retention. Deletion of the ISS in colon cancer cells leads to increases in OGT, but O-GlcNAc homeostasis is maintained by concomitant increases in OGA protein. However, the ISS-deleted cells are hypersensitive to OGA inhibition in culture and in soft agar. Moreover, growth of xenograft tumors from ISS-deleted cells is compromised in mice treated with an OGA inhibitor. Thus, ISS-mediated regulation of OGT intron retention is a key component in OGT expression and maintaining O-GlcNAc homeostasis.

Graphical abstract

Teaser

O-GlcNAc transferase (OGT) modifies cellular proteins, but the mechanisms that regulate OGT expression remain unclear. Park et al. show intron retention of the OGT transcript is responsive to cellular O-GlcNAc levels. They further define an intronic splicing silencer that is necessary to maintain O-GlcNAc homeostasis in cells and tumors.


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Attenuation of Synaptic Potentials in Dendritic Spines

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Taekyung Kwon, Masayuki Sakamoto, Darcy S. Peterka, Rafael Yuste
Dendritic spines receive the majority of excitatory inputs in many mammalian neurons, but their biophysical properties and exact role in dendritic integration are still unclear. Here, we study spine electrical properties in cultured hippocampal neurons using an improved genetically encoded voltage indicator (ArcLight) and two-photon glutamate uncaging. We find that back-propagating action potentials (bAPs) fully invade dendritic spines. However, uncaging excitatory post-synaptic potentials (uEPSPs) generated by glutamate photorelease, ranging from 4 to 27 mV in amplitude, are attenuated by up to 4-fold as they propagate to the parent dendrites. Finally, the simultaneous occurrence of bAPs and uEPSPs results in sublinear summation of membrane potential. Our results demonstrate that spines can behave as electric compartments, reducing the synaptic inputs injected into the cell, while receiving bAPs are unmodified. The attenuation of EPSPs by spines could have important repercussions for synaptic plasticity and dendritic integration.

Graphical abstract

Teaser

Using genetically encoded voltage indicators and two-photon glutamate uncaging, Kwon et al. find that synaptic potentials are severely attenuated by dendritic spines.


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Dual Effects of TARP γ-2 on Glutamate Efficacy Can Account for AMPA Receptor Autoinactivation

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Ian D. Coombs, David M. MacLean, Vasanthi Jayaraman, Mark Farrant, Stuart G. Cull-Candy
Fast excitatory transmission in the CNS is mediated mainly by AMPA-type glutamate receptors (AMPARs) associated with transmembrane AMPAR regulatory proteins (TARPs). At the high glutamate concentrations typically seen during synaptic transmission, TARPs slow receptor desensitization and enhance mean channel conductance. However, their influence on channels gated by low glutamate concentrations, as encountered during delayed transmitter clearance or synaptic spillover, is poorly understood. We report here that TARP γ-2 reduces the ability of low glutamate concentrations to cause AMPAR desensitization and enhances channel gating at low glutamate occupancy. Simulations show that, by shifting the balance between AMPAR activation and desensitization, TARPs can markedly facilitate the transduction of spillover-mediated synaptic signaling. Furthermore, the dual effects of TARPs can account for biphasic steady-state glutamate concentration-response curves—a phenomenon termed "autoinactivation," previously thought to reflect desensitization-mediated AMPAR/TARP dissociation.

Graphical abstract

Teaser

AMPA receptors are regulated by accessory proteins, including TARP γ-2. Coombs et al. show how γ-2 can give rise to receptor behavior previously attributed to glutamate-induced dissociation of the AMPAR/TARP assembly. By favoring the gating of singly liganded receptors, γ-2 is predicted to facilitate synaptic signaling by low concentrations of glutamate.


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Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Véronique Lisi, Bhagat Singh, Michel Giroux, Elmer Guzman, Michio W. Painter, Yung-Chih Cheng, Eric Huebner, Giovanni Coppola, Michael Costigan, Clifford J. Woolf, Kenneth S. Kosik
Peripheral nerve regeneration after injury requires a broad program of transcriptional changes. We investigated the basis for the enhanced nerve regenerative capacity of the CAST/Ei mouse strain relative to C57BL/6 mice. RNA sequencing of dorsal root ganglia (DRG) showed a CAST/Ei-specific upregulation of Ascl1 after injury. Ascl1 overexpression in DRG neurons of C57BL/6 mice enhanced their neurite outgrowth. Ascl1 is regulated by miR-7048-3p, which is downregulated in CAST/Ei mice. Inhibition of miR-7048-3p enhances neurite outgrowth. Following injury, CAST/Ei neurons largely retained their mature neuronal profile as determined by single-cell RNA- seq, whereas the C57BL/6 neurons acquired an immature profile. These findings suggest that one facet of the enhanced regenerative phenotype is preservation of neuronal identity in response to injury.

Graphical abstract

Teaser

Lisi et al. find that increased Ascl1 expression is associated with the superior regenerative capacity of CAST/Ei mice. Single-cell RNA-seq demonstrated that CAST/Ei mice retained more mature neurons after injury than did C57BL/6 mice, thereby suggesting that genetic drivers of the enhanced regenerative phenotype include mechanisms to preserve neuronal identity after injury.


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Loss of Brap Results in Premature G1/S Phase Transition and Impeded Neural Progenitor Differentiation

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Alison A. Lanctot, Yan Guo, Yicong Le, Brittany M. Edens, Richard S. Nowakowski, Yuanyi Feng
Cells initiate fate decisions during G1 phase by converting extracellular signals into distinctive cell cycle kinetics. The DNA replication timing is determined in G1 phase; lengthened G1 and hastened S phases correlate with increased neurogenic propensity of neural progenitor cells (NPCs), although the underlying molecular control remains elusive. Here, we report that proper G1 phase completion in NPCs requires Brap, a Ras-Erk signaling modulator with ubiquitin E3 ligase activity. We identified Skp2 and Skp2-associated SCF ubiquitin ligase as a key target of Brap-mediated polyubiquitination. Loss of Brap resulted in elevated Skp2, which increased p27^Kip1 destruction, leading to G1 phase truncation and premature S phase entry. The aberrantly executed G1 in Brap-mutant NPCs, followed by hindered S phase progression and increased G2 phase arrest, which together prolonged the cell cycle, impeded neuronal differentiation and culminated in microcephaly. These findings demonstrate that neuronal differentiation is potentiated during G1 phase by Brap-directed cascade of events in cell signaling and protein turnover.

Graphical abstract

Teaser

Lanctot et al. show that the capacity of neural progenitors to generate cerebral cortical neurons relies on the integration of cell signaling and ubiquitin-mediated protein turnover to complete G1 phase of the cell cycle.


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CFP1 Regulates Histone H3K4 Trimethylation and Developmental Potential in Mouse Oocytes

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Chao Yu, Xiaoying Fan, Qian-Qian Sha, Hui-Han Wang, Bo-Tai Li, Xing-Xing Dai, Li Shen, Junping Liu, Lie Wang, Kui Liu, Fuchou Tang, Heng-Yu Fan
Trimethylation of histone H3 at lysine-4 (H3K4me3) is associated with eukaryotic gene promoters and poises their transcriptional activation during development. To examine the in vivo function of H3K4me3 in the absence of DNA replication, we deleted CXXC finger protein 1 (CFP1), the DNA-binding subunit of the SETD1 histone H3K4 methyltransferase, in developing oocytes. We find that CFP1 is required for H3K4me3 accumulation and the deposition of histone variants onto chromatin during oocyte maturation. Decreased H3K4me3 in oocytes caused global downregulation of transcription activity. Oocytes lacking CFP1 failed to complete maturation and were unable to gain developmental competence after fertilization, due to defects in cytoplasmic lattice formation, meiotic division, and maternal-zygotic transition. Our study highlights the importance of H3K4me3 in continuous histone replacement for transcriptional regulation, chromatin remodeling, and normal developmental progression in a non-replicative system.

Graphical abstract

Teaser

Yu et al. define CFP1 as a key regulator of oocyte chromatin changes and developmental potential. Deletion of CFP1 in oocytes causes decreased H3K4me3 levels and transcription, in turn, leading to cytoskeletal defects, meiotic division, maternal-zygotic transition, and, ultimately, infertility.


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Human TFIIH Kinase CDK7 Regulates Transcription-Associated Chromatin Modifications

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Christopher C. Ebmeier, Benjamin Erickson, Benjamin L. Allen, Mary A. Allen, Hyunmin Kim, Nova Fong, Jeremy R. Jacobsen, Kaiwei Liang, Ali Shilatifard, Robin D. Dowell, William M. Old, David L. Bentley, Dylan J. Taatjes
CDK7 phosphorylates the RNA polymerase II (pol II) C-terminal domain CTD and activates the P-TEFb-associated kinase CDK9, but its regulatory roles remain obscure. Here, using human CDK7 analog-sensitive (CDK7as) cells, we observed reduced capping enzyme recruitment, increased pol II promoter-proximal pausing, and defective termination at gene 3′ ends upon CDK7 inhibition. We also noted that CDK7 regulates chromatin modifications downstream of transcription start sites. H3K4me3 spreading was restricted at gene 5′ ends and H3K36me3 was displaced toward gene 3′ ends in CDK7as cells. Mass spectrometry identified factors that bound TFIIH-phosphorylated versus P-TEFb-phosphorylated CTD (versus unmodified); capping enzymes and H3K4 methyltransferase complexes, SETD1A/B, selectively bound phosphorylated CTD, and the H3K36 methyltransferase SETD2 specifically bound P-TEFb-phosphorylated CTD. Moreover, TFIIH-phosphorylated CTD stimulated SETD1A/B activity toward nucleosomes, revealing a mechanistic basis for CDK7 regulation of H3K4me3 spreading. Collectively, these results implicate a CDK7-dependent "CTD code" that regulates chromatin marks in addition to RNA processing and pol II pausing.

Graphical abstract

Teaser

Ebmeier et al. use targeted proteomics to identify distinct interactomes for full-length mammalian pol II CTD phosphorylated by TFIIH or P-TEFb. In vitro and cell-based assays uncover expanded roles for the TFIIH-associated kinase CDK7, including regulation of SETD1A/B methyltransferase activity and regulation of transcription-associated histone modifications (i.e., H3K4me3 and H3K36me3).


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Dual RNA Processing Roles of Pat1b via Cytoplasmic Lsm1-7 and Nuclear Lsm2-8 Complexes

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Caroline Vindry, Aline Marnef, Helen Broomhead, Laure Twyffels, Sevim Ozgur, Georg Stoecklin, Miriam Llorian, Christopher W. Smith, Juan Mata, Dominique Weil, Nancy Standart
Pat1 RNA-binding proteins, enriched in processing bodies (P bodies), are key players in cytoplasmic 5′ to 3′ mRNA decay, activating decapping of mRNA in complex with the Lsm1-7 heptamer. Using co-immunoprecipitation and immunofluorescence approaches coupled with RNAi, we provide evidence for a nuclear complex of Pat1b with the Lsm2-8 heptamer, which binds to the spliceosomal U6 small nuclear RNA (snRNA). Furthermore, we establish the set of interactions connecting Pat1b/Lsm2-8/U6 snRNA/SART3 and additional U4/U6.U5 tri-small nuclear ribonucleoprotein particle (tri-snRNP) components in Cajal bodies, the site of snRNP biogenesis. RNA sequencing following Pat1b depletion revealed the preferential upregulation of mRNAs normally found in P bodies and enriched in 3′ UTR AU-rich elements. Changes in >180 alternative splicing events were also observed, characterized by skipping of regulated exons with weak donor sites. Our data demonstrate the dual role of a decapping enhancer in pre-mRNA processing as well as in mRNA decay via distinct nuclear and cytoplasmic Lsm complexes.

Graphical abstract

Teaser

Pat1 RNA-binding proteins, enriched in P bodies, are key players in cytoplasmic 5′ to 3′ mRNA decay. Vindry et al. demonstrate an additional role of human Pat1b in alternative splicing via the nuclear Lsm complex and identify distinct mRNA targets of Pat1b-dependent splicing and decay regulation.


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Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Hao Song, Jianxun Qi, Haixia Xiao, Yuhai Bi, Wei Zhang, Ying Xu, Fei Wang, Yi Shi, George F. Gao
Low-pathogenicity avian influenza viruses (LPAIVs) have caused a global concern to public health since the first novel LPAIV H7N9 outbreak occurred. The receptor-binding properties of the viral hemagglutinin are one key factor for efficient transmission and infection in humans. Recent evidence shows that H4 subtype viruses have been widely circulating in domestic poultry and human asymptomatic infections might have occurred. Here, we evaluated the receptor-binding properties of two representative isolates, avian H4N6 (containing Q226 and G228) and swine H4N6 (containing L226 and S228), and found that the avian isolate preferentially binds to avian receptors, whereas the swine isolate preferentially binds to human receptors. The Q226L and G228S substitutions are pivotal for the receptor-binding switch, which resulted in similar human receptor-binding features to the pandemic H2 and H3, implying that H4 has the potential to cause human infections. This early-warning study calls for future extensive surveillance.

Graphical abstract

Teaser

The shift in the receptor-binding specificity of avian influenza virus is critical for the jump from avian to human hosts. Based on receptor-binding analysis and structural studies, Song et al. report the mechanisms behind the avian-to-human receptor-binding adaptation by influenza A virus hemagglutinin H4.


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Single-Cell Landscape of Transcriptional Heterogeneity and Cell Fate Decisions during Mouse Early Gastrulation

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Hisham Mohammed, Irene Hernando-Herraez, Aurora Savino, Antonio Scialdone, Iain Macaulay, Carla Mulas, Tamir Chandra, Thierry Voet, Wendy Dean, Jennifer Nichols, John C. Marioni, Wolf Reik
The mouse inner cell mass (ICM) segregates into the epiblast and primitive endoderm (PrE) lineages coincident with implantation of the embryo. The epiblast subsequently undergoes considerable expansion of cell numbers prior to gastrulation. To investigate underlying regulatory principles, we performed systematic single-cell RNA sequencing (seq) of conceptuses from E3.5 to E6.5. The epiblast shows reactivation and subsequent inactivation of the X chromosome, with Zfp57 expression associated with reactivation and inactivation together with other candidate regulators. At E6.5, the transition from epiblast to primitive streak is linked with decreased expression of polycomb subunits, suggesting a key regulatory role. Notably, our analyses suggest elevated transcriptional noise at E3.5 and within the non-committed epiblast at E6.5, coinciding with exit from pluripotency. By contrast, E6.5 primitive streak cells became highly synchronized and exhibit a shortened G1 cell-cycle phase, consistent with accelerated proliferation. Our study systematically charts transcriptional noise and uncovers molecular processes associated with early lineage decisions.

Graphical abstract

Teaser

Mohammed et al. chart mouse embryonic development from implantation to early gastrulation at single-cell resolution. They describe regulatory processes associated with lineage commitment. An increased level of transcriptional noise is observed prior to lineage commitment, an observation that provides fresh insights into cell fate decision-making processes.


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Impact of Alternative Splicing on the Human Proteome

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Yansheng Liu, Mar Gonzàlez-Porta, Sergio Santos, Alvis Brazma, John C. Marioni, Ruedi Aebersold, Ashok R. Venkitaraman, Vihandha O. Wickramasinghe
Alternative splicing is a critical determinant of genome complexity and, by implication, is assumed to engender proteomic diversity. This notion has not been experimentally tested in a targeted, quantitative manner. Here, we have developed an integrative approach to ask whether perturbations in mRNA splicing patterns alter the composition of the proteome. We integrate RNA sequencing (RNA-seq) (to comprehensively report intron retention, differential transcript usage, and gene expression) with a data-independent acquisition (DIA) method, SWATH-MS (sequential window acquisition of all theoretical spectra-mass spectrometry), to capture an unbiased, quantitative snapshot of the impact of constitutive and alternative splicing events on the proteome. Whereas intron retention is accompanied by decreased protein abundance, alterations in differential transcript usage and gene expression alter protein abundance proportionate to transcript levels. Our findings illustrate how RNA splicing links isoform expression in the human transcriptome with proteomic diversity and provides a foundation for studying perturbations associated with human diseases.

Graphical abstract

Teaser

Liu et al. have developed an integrative approach to ask whether perturbations in mRNA splicing patterns alter the composition of the proteome. Their findings illustrate how RNA splicing links isoform expression in the human transcriptome with proteomic diversity and provides a foundation for studying perturbations associated with human diseases.


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Multi-level Strategy for Identifying Proteasome-Catalyzed Spliced Epitopes Targeted by CD8+ T Cells during Bacterial Infection

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Anouk C.M. Platteel, Juliane Liepe, Kathrin Textoris-Taube, Christin Keller, Petra Henklein, Hanna H. Schalkwijk, Rebeca Cardoso, Peter M. Kloetzel, Michele Mishto, Alice J.A.M. Sijts
Proteasome-catalyzed peptide splicing (PCPS) generates peptides that are presented by MHC class I molecules, but because their identification is challenging, the immunological relevance of spliced peptides remains unclear. Here, we developed a reverse immunology-based multi-level approach to identify proteasome-generated spliced epitopes. Applying this strategy to a murine Listeria monocytogenes infection model, we identified two spliced epitopes within the secreted bacterial phospholipase PlcB that primed antigen-specific CD8⁺ T cells in L. monocytogenes-infected mice. While reacting to the spliced epitopes, these CD8⁺ T cells failed to recognize the non-spliced peptide parts in the context of their natural flanking sequences. Thus, we here show that PCPS expands the CD8⁺ T cell response against L. monocytogenes by exposing spliced epitopes on the cell surface. Moreover, our multi-level strategy opens up opportunities to systematically investigate proteins for spliced epitope candidates and thus strategies for immunotherapies or vaccine design.

Graphical abstract

Teaser

Proteasomes both degrade proteins and ligate generated products, creating "spliced peptides" composed of distant protein parts. Platteel et al. now describe a multi-level strategy for identifying proteasome-generated spliced T cell epitopes. This work suggests ways of defining spliced epitopes within any antigen of interest and to determine their immunological relevance.


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Measurement accuracy of alveolar soft tissue contour using a laboratory laser scanner

Abstract

Steric analysis of morphological changes is important for evaluation of surgical techniques. This study was performed to assess the measurement accuracy of alveolar soft tissue contour with a laboratory laser scanner. The width of the maxillary alveolar soft tissue contour was evaluated in 20 volunteers. Measurement sites were established in the alveolar soft tissue contour of the maxillary incisor and canine areas. Each site was evaluated by direct measurement with a microcaliper for each subject (DMM) and image measurement using a laboratory laser scanner (IMS). The accuracy of measurement methods was evaluated. Additionally, two plaster models obtained from the same subjects were scanned and superimposed, and the nonoverlapping areas were measured. Each measurement method exhibited a strong correlation (r = 0.89). The interclass correlation coefficient (single measure) between examiners was also high for each measurement method (PMM 0.978; IMS 0.997). In the superimposed images of the two plaster models, the distance of the nonoverlapping region was only 0.06 ± 0.08 mm in the labial aspect and 0.07 ± 0.09 mm in the palatal aspect. The image measurement of the scanning data shows high accuracy in evaluation of the alveolar soft tissue contour. This technique is useful for evaluation of chronological changes in the alveolar contour after soft and hard tissue augmentation.

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A stepwise under-prepared osteotomy technique improves primary stability in shallow-placed implants: a preliminary study for simultaneous vertical ridge augmentation

Abstract

Simultaneous vertical ridge augmentation (VRA) can reduce treatment procedures and surgery time, but the concomitant reduction in primary stability (PS) of a shallow-placed implant imparts risk to its prognosis. Although several studies have reported improvements in PS, there is little information from any simultaneous VRA model. This study aimed to evaluate whether tapered implants with stepwise under-prepared osteotomy could improve the PS of shallow-placed implants in an in vitro model of simultaneous VRA. Tapered implants (Straumann^® Bone Level Tapered implant; BLT) and hybrid implants (Straumann^® Bone Level implant; BL) were investigated in this study. A total of 80 osteotomies of different depths (4, 6, 8, 10 mm) were created in rigid polyurethane foam blocks, and each BLT and BL was inserted by either standard (BLT-S, BL-S) or a stepwise under-prepared (BLT-U, BL-U) osteotomy protocol. The PS was evaluated by measuring maximum insertion torque (IT), implant stability quotient (ISQ), and removal torque (RT). The significance level was set at P < 0.05. There were no significant differences in IT, ISQ or RT when comparing BLT-S and BL-S or BLT-U and BL-U at placement depths of 6 and 8 mm. When comparison was made between osteotomy protocols, IT was significantly greater in BLT-U than in BLT-S at all placement depths. A stepwise under-prepared osteotomy protocol improves initial stability of a tapered implant even in a shallow-placed implant model. BLT-U could be a useful protocol for simultaneous VRA.

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Uncertain Associations of Major Bleeding and Concurrent Use of Antiplatelet Agents and Chinese Medications: A Nested Case-Crossover Study

Despite the evidence that some commonly used Chinese medications (CMs) have antiplatelet/anticoagulant effects, many patients still used antiplatelets combined with CMs. We conducted a nested case-crossover study to examine the associations between the concomitant use of antiplatelets and CMs and major bleeding using population-based health database in Taiwan. Among the cohort of 79,463 outpatients prescribed antiplatelets (e.g., aspirin and clopidogrel) continuously, 1,209 patients hospitalized with new occurring bleeding in 2012 and 2013 were included. Those recruited patients served as their own controls to compare different times of exposure to prespecified CMs (e.g., Asian ginseng and dong quai) and antiplatelet agents. The periods of case, control 1, and control 2 were defined as 1–4 weeks, 6–9 weeks, and 13–16 weeks before hospitalization, respectively. Conditional logistic regression analyses found that concurrent use of antiplatelet drugs with any of the prespecified CMs in the case period might not significantly increase the risks of bleeding over that in the control periods (OR = 1.00, 95% CI 0.51 to 1.95 and OR = 1.13, 95% CI 0.65 to 1.97). The study showed no strong relationships between hospitalization for major bleeding events and concurrent use of antiplatelet drugs with the prespecified CMs.

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Tibetan Microblog Emotional Analysis Based on Sequential Model in Online Social Platforms

With the development of microblogs, selling and buying appear in online social platforms such as Sina Weibo and Wechat. Besides Mandarin, Tibetan language is also used to describe products and customers' opinions. In this paper, we are interested in analyzing the emotions of Tibetan microblogs, which are helpful to understand opinions and product reviews for Tibetan customers. It is challenging since existing studies paid little attention to Tibetan language. Our key idea is to express Tibetan microblogs as vectors and then classify them. To express microblogs more fully, we select two kinds of features, which are sequential features and semantic features. In addition, our experimental results on the Sina Weibo dataset clearly demonstrate the effectiveness of feature selection and the efficiency of our classification method.

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A comparison of the tongue-in-groove and columellar strut in creating and maintaining tip projection and rotation: a randomized single blind trial

Abstract

Background

Rhinoplasty is one of the most challenging esthetic operations. The ability to achieve precise and predictable changes in the shape and position of the nasal tip is still among the demanding areas of rhinoplasty. Tongue in groove (TIG) and columellar strut are two of the many techniques to ensure an adequate nasal tip projection and rotation; however, there is little evidence to support long-term efficacy of these techniques.

Methods

In a clinical trial, 80 cases who were rhinoplasty candidates were studied prospectively. They were randomly divided into two groups according to the use of columellar strut and TIG. The outcome measures were gaining and maintaining tip projection and rotation in the long term. Standardized photographs before and 6 and 12 months after the surgery were the measurements to compare the results between the two groups, which were evaluated for nasolabial angle and projection. Also, the patients' satisfaction with beauty and nasal obstruction were assessed using the VAS (Visual Analogue Scale).

Results

Forty patients were operated using the columellar strut technique while the TIG method was used in 40 cases. Preoperatively, tip rotation, tip projection, and other characteristics were not significantly different between the two groups. Postoperatively, the patients' esthetic satisfaction was significantly greater in the TIG group 6 and 12 months after the surgery (P value = 0.001). The rest of the evaluated variables did not have any significant differences between the two groups.

Conclusions

It seems that both columellar strut and tongue in groove methods are effective techniques in maintaining tip projection and/or rotation in rhinoplasty. Using the tongue in groove technique in qualified hands may give significantly better esthetic satisfaction to patients than the columellar strut technique.

Level of evidence: Level I, therapeutic study.

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First reported case of magnesium-made bioresorbable scaffold to treat spontaneous left anterior descending coronary artery dissection

Abstract

Spontaneous coronary artery dissection (SCAD) is a rare cause of Acute Coronary Syndrome. Although its treatment is still debated, use of Bioreasorbable Scaffold was recently advocated as an attractive option in this setting. We report the first case, to our knowledge, of a new magnesium-made Bioresorbable Scaffold implantation in a young woman presenting with Non-ST- Elevation Myocardial Infarction and a rapid worsening SCAD.

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Doppler echocardiography underestimates the prevalence and magnitude of mid-cavity obstruction in patients with symptomatic hypertrophic cardiomyopathy

Abstract

Objectives

To evaluate utility of Doppler echocardiography in the assessment of left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy (HCM).

Background

LVMCO is a relatively under-diagnosed complication of HCM and may occur alone or in combination with LV outflow tract obstruction (LVOTO). Identifying and quantifying LVMCO and differentiating it from LVOTO has important implications for patient management. We aimed to assess diagnostic performance of Doppler echocardiography in the assessment of suspected LV obstruction.

Methods

Forty symptomatic HCM patients with suspected obstruction underwent cardiac catheterization, and comparison of location and magnitude of Doppler derived gradients with synchronous invasive measurements (reference standard), at rest and isoprenaline stress (IS).

Results

Doppler's diagnostic accuracy for any obstruction (≥30 mmHg) in this cohort was 75% with false positive and false negative rates of 2.5 and 22.5%, respectively. During subanalysis, Doppler's diagnostic accuracy for isolated LVOTO in this selected cohort is 83% with false positive and false negative rates of 4 and 12.5%, respectively. For LVMCO, the accuracy is only 50%, with false positive and false negative rates of 10 and 40%, respectively.

Doppler gradients for isolated LVOTO were similar to invasive: 85 ± 51 and 87 ± 35 mmHg, respectively (P = 0.77). Doppler gradients in LVMCO were consistently lower than invasive: 45 ± 38 and 81 ± 31 mmHg, respectively (P = 0.0002). Mid-systolic flow cessation and/or contamination of spectral signals were identified as causes of Doppler-derived inaccuracies.

Conclusions

Doppler echocardiography under-diagnoses and underestimates severity of LVMCO in symptomatic HCM patients. Recognition of abrupt mid-systolic flow cessation and invasive measurements may improve detection of LVMCO in HCM.

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Techniques and outcomes of paravalvular leak repair after transcatheter aortic valve replacement

Abstract

Objectives

To investigate the feasibility, procedural success, and outcomes of paravalvular leak (PVL) closure in patients with prior transcatheter aortic valve replacement (TAVR).

Background

PVL after TAVR is associated with adverse patient outcomes and increased mortality. Percutaneous PVL closure has emerged as a therapeutic strategy for addressing this issue, but data for transcatheter PVL repair after TAVR remains limited.

Methods

This is a single center retrospective review of PVL closure after TAVR. Patients with balloon-expandable or self-expanding prostheses were included. Baseline patient demographics, procedural characteristics, complications, and clinical outcomes were reviewed.

Results

A total of 18 patients with clinically significant PVL after TAVR referred for PVL closure were identified during the study period. Procedural success resulting in successful transcatheter occluder plug delivery was 78% (14 cases). Balloon postdilatation (2/4) and valve-in-valve (2/4) were used effectively in the remaining patients after an unsuccessful PVL closure attempt. PVL grading by echocardiography decreased from moderate or severe to < moderate in 13 patients (72%). Adverse events including cardiac tamponade and acute kidney injury occurred in 1 case each. One-month all-cause mortality was 11%.

Conclusion

In selected patients, percutaneous PVL repair following TAVR is feasible and effective for both balloon-expandable and self-expanding prostheses. Most patients undergoing PVL closure after TAVR require a single occluder plug placement for reduction in PVL to mild or less.

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Transulnar cardiac catheterization and percutaneous coronary intervention: techniques, transradial comparisons, anatomical considerations, and comprehensive literature review

Abstract

Ulnar arterial access for cardiac catheterization and intervention is an alternative approach compared with radial or femoral access. Ulnar access is infrequently performed since the radial artery is readily palpable and is commonly used worldwide to minimize vascular complications from femoral access. Nevertheless, ulnar access provides a suitable access site in patients who are poor candidates for femoral access, have pre-existing radial occlusion, radial artery hypoplasia or hyperplasia from prior radial artery procedures, radial stenosis, radial loops, radial tortuosity, small radial arteries, and/or have future need for radial graft for dialysis or coronary artery bypass graft. Furthermore, femoral access is the standard default option if radial access fails. Consequently, learning ulnar access provides a suitable forearm alternative to avoid femoral access when deemed high risk or undesirable. This review discusses the techniques of ulnar access, advantages and disadvantages of ulnar versus radial access, the clinical trials on ulnar cardiac catheterization and its associated complications.

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Transseptal puncture using surgical electrocautery in children and adults with and without complex congenital heart disease

Abstract

Background

Atrial transseptal puncture (TSP) for cardiac catheterization procedures remain challenging in children and adults with complex congenital heart disease (CHD).

Objectives

We sought to evaluate our experience using radiofrequency (RF) current via surgical electrocautery needle for TSP to facilitate diagnostic and interventional procedures.

Methods

Retrospective chart review of all patients (pts) who underwent TSP using RF energy (10–25 W) via surgical electrocautery from three centers from January 2011 to January 2017 were evaluated. Echocardiograms were reviewed to define the atrial septum as normal and complex (thin aneurysmal, thick/fibrotic, synthetic patch material, and extra cardiac conduit).

Results

A total of 54 pts underwent 55 successful TSP. Median age was 12.5 years (1 day–54 years) and weight was 52.7 kg (2–162). Indications for TSP included; EP study and ablation procedures in structurally normal hearts (n = 24) and in complex atrial septum/CHD and structural heart disease pts (n = 30): Electrophysiology study and ablation in 4, diagnostic catheterization in 9, and interventional procedures in 17 pts were performed. Atrial TSP was successful in 54/55 (98%). Atrial perforation with tiny-small pericardial effusion not requiring intervention was noted in 2 pts. TSP was unsuccessful in one critically ill neonate with unobstructed TAPVR and restricted atrial septum who experienced cardiac arrest requiring CPR, ECMO, and emergent surgery.

Conclusions

RF current delivery using surgical electrocautery for TSP is a feasible and an effective option in patients with complex CHD for diagnostic, interventional, and electrophysiology procedures.

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Coronary atherectomy is associated with improved procedural and clinical outcomes among patients with calcified coronary lesions: Insights from the VA CART program

Abstract

Objectives

We sought to evaluate the prevalence of calcified coronary lesions and the association between the use of atherectomy and clinical outcomes.

Background

Calcified coronary arteries are associated with an increased risk of procedural complications during percutaneous coronary intervention (PCI). The outcomes of coronary atherectomy for adjunctive treatment of calcified coronary lesions are not well described.

Methods

We identified all patients treated for calcified coronary lesions at VA hospitals. A propensity weighted cohort was created for those treated with or without adjunctive atherectomy to evaluate the complications and outcomes between groups.

Results

From 2007 to 2015, 9,719 patients underwent single-vessel PCI for treatment of naïve native calcific coronary lesions. The proportion of patients undergoing revascularization of calcified lesions increased over the study period (P = 0.03) and 1,731 patients (18%) were treated with atherectomy. Adjunctive atherectomy was more likely to be used in high-risk lesions (76.5% vs. 46.8%, P < 0.001). After propensity weighting, coronary atherectomy was associated with a 38% decrease in the odds of procedural complications and a 54% decrease in the odds of clinical complications (both P = 0.005). There was no difference in rates of 2-year death (HR: 1.07; 95% CI: 0.92–1.24), myocardial infarction (HR: 0.96; 95% CI: 0.75–1.23) or target vessel revascularization (HR: 0.96; 95% CI: 0.78–1.19)

Conclusions

Percutaneous treatment of calcified coronary lesions has increased over time. The adjunctive use of coronary atherectomy was associated with a reduction in procedural complications among patients with calcified coronary arteries. Two-year TVR, MI and overall mortality were similar between the two groups.

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The relationship between the basal coronary translesional pressure gradient and fractional flow reserve

Aim

Fractional flow reserve (FFR) allows for physiological definition of coronary lesion severity but requires induction of maximal coronary circulation hyperemia with administration of adenosine leading to coronary resistive vessel vasodilatation. However, the hyperemic response to adenosine, and therefore the calculation of FFR, may be affected by dysfunction of the coronary microvasculature. The aim was to define the relationship between basal P_d/P_a and FFR and identify lesion-independent predictors of the change in P_d/P_a with hyperemia.

Methods and Results

One hundred and sixty-six consecutive patients undergoing FFR measurement were prospectively enrolled (mean age 62.6 ± 10.3 years, 27% females). Basal P_d/P_a, FFR, and delta P_d/P_a (difference between basal P_d/P_a and FFR) were recorded. Independent predictors of delta P_d/P_a included angiographic lesion severity, lesion length, gender, body mass index, and total cholesterol:HDL cholesterol ratio. The best basal P_d/P_a cutoff value to predict lesion physiological significance was 0.87 (positive predictive value of 100% for an FFR value ≤0.80) and the best cutoff for nonsignificance was 0.93 (negative predictive value of 98% for an FFR value >0.80).

Conclusion

The delta P_d/P_a may be affected by patient gender, body mass index, and cholesterol profile. A basal P_d/P_a value of ≥0.93 is highly predictive of an FFR >0.80. Conversely, a basal P_d/P_a value of ≤0.87 is highly predictive of an FFR ≤0.80. © 2017 Wiley Periodicals, Inc.

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Factors associated with performing urgent coronary angiography in out-of-hospital cardiac arrest patients

Abstract

Objectives

Factors associated with performing urgent coronary angiography (UCA) in patients with out-of-hospital cardiac arrest (OHCA) were identified.

Background

Current guidelines for resuscitated OHCA patients recommend UCA if there is ST-elevation on post-arrest electrocardiogram or high suspicion of acute myocardial infarction. Some have advocated for UCA in all OHCA regardless of suspected etiology. The reasons for variations in performing UCA are not well understood.

Methods

A retrospective analysis of subjects presenting with resuscitated OHCA to a single academic medical center from 12/15/2007 to 8/31/2014 was conducted. Demographic and clinical characteristics of patients undergoing UCA, defined as angiography within 6 hr of presentation, were compared with those not undergoing UCA. Logistic regression was used to determine predictors of UCA.

Results

A total of 323 resuscitated OHCA patients (mean age, 64 years; women, 35%) were included in the analysis; 107 (33.1%) underwent coronary angiography during their hospitalization and 66 (20.4%) underwent UCA. Multivariable adjusted factors associated with UCA were ST-elevation [odds ratio (OR) 14.66, 95% confidence interval (CI) 6.28–34.24, P < 0.001], initial shockable rhythm (OR 3.69, 95% CI 1.52–8.97, P = 0.004), and history of coronary artery disease (CAD) (OR 3.37, 95% CI 1.43–7.95, P = 0.005). Higher age (OR 0.71 per decade, 95% CI 0.55–0.92, P = 0.01) and obvious non-cardiac cause of arrest (OR 0.08, 95% CI 0.02–0.38, P = 0.001) were negatively associated with UCA.

Conclusions

In resuscitated out-of-hospital cardiac arrest patients, ST-elevation, shockable rhythm, and history of CAD were associated with performing urgent coronary angiography; older patients and those with obvious non-cardiac causes of arrest were negatively associated.

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Angiographic and clinical performance of polymer-free biolimus-eluting stent in patients with ST-segment elevation acute myocardial infarction in a metropolitan public hospital: The BESAMI MUCHO study

Abstract

Objectives

This study aimed at assessing the performance of a new generation polymer-free biolimus-eluting stent (BES) in real-world patients with ST-segment elevation myocardial infarction (STEMI).

Background

Polymers components of early-generation drug-eluting stents have been implicated in the pathogenesis of delayed arterial healing, vessel remodeling, and delayed stent thrombosis. Recently, a novel polymer-free BES has shown excellent clinical performance in clinical trial setting.

Methods

Overall, 175 consecutive patients (64 ± 14 years, 141 men) treated with the BioFreedom (Biosensors Europe, Morges, Switzerland) polymer-free BES because of STEMI were included in this study. The primary endpoint was the rate of major adverse cardiac events (MACE), a composite of cardiac death, recurrent myocardial infarction, and ischemia-driven target vessel revascularization at 1 year follow-up. A subgroup of patients underwent 6-month angiographic follow-up. Dual antiplatelet therapy was prescribed for 12 months after STEMI.

Results

At 1 year, the cumulative rate of MACE was 4.6%. One patient (0.6%) had an arrhythmic cardiac death and five (2.9%) had ischemia-driven target vessel revascularization, although only three (1.7%) had target lesion revascularization. Two (1.1%) patients had acute stent thrombosis yielding nonfatal myocardial infarction. In 70 patients (63 ± 14 years, 61 men), quantitative coronary angiography at 6-month follow-up revealed diameter stenosis of 24.1 ± 13.7% and minimal lumen diameter of 2.29 ± 0.56 mm, yielding a late lumen loss of 0.13 ± 0.14 mm.

Conclusions

In real-world setting, implantation of a new-generation polymer-free BES during STEMI is associated with favorable clinical and angiographic results, pointing toward the overall efficacy and safety of the device in complex clinical scenarios.

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Simulation-based education leads to decreased use of fluoroscopy in diagnostic coronary angiography

Abstract

Objectives

The aim of this study is to determine whether simulation-based education (SBE) translates into reduced procedure time, radiation, and contrast use in actual clinical care.

Background

As a high volume procedure often performed by novice cardiology fellows, diagnostic coronary angiography represents an excellent target for SBE. Reports of SBE in interventional cardiology are limited and there is little understanding of the potential downstream clinical impact of these interventions.

Methods

All diagnostic coronary angiograms performed at a single center between January 1, 2011 and June 30, 2015 were analyzed. Random effects linear regression models were used to compare outcomes between procedures performed by 12 cardiology fellows who underwent simulation-based training and those performed by 20 traditionally trained fellows.

Results

Thirty-two cardiology fellows performed 2,783 diagnostic coronary angiograms. Procedures performed by fellows trained with SBE were shorter (mean of 23.98 min vs. 24.94 min, P = 0.034) and were performed with decreased radiation (mean of 56,348 mGycm² vs. 66,120 mGycm², P < 0.001). After controlling for year in training, procedure year, access site, and supervising attending physician, training on the simulator was independently associated with 117 fewer seconds of fluoroscopy time per procedure (P = 0.04).

Conclusions

Diagnostic coronary angiography SBE is associated with decreased use of fluoroscopy in downstream clinical care. SBE may be a useful tool to reduce radiation exposure in the cardiac catheterization laboratory

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