Πέμπτη 6 Σεπτεμβρίου 2018
Reply: Two cases of CLIPPERS with increased number of perivascular CD20-positive B lymphocytes
Sir,
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Two cases of CLIPPERS with increased number of perivascular CD20-positive B lymphocytes
Sir,
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Feasibility study of mindfulness-based cognitive therapy for anxiety disorders in a Japanese setting
Mindfulness-based cognitive therapy (MBCT) could be a treatment option for anxiety disorders. Although its effectiveness under conditions of low pharmacotherapy rates has been demonstrated, its effectiveness u...
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Initial value problems for system of differential-algebraic equations in Maple
In this paper, we discuss a Maple package, deaSolve, of the symbolic algorithm for solving an initial value problem for the system of linear differential-algebraic equations with constant coefficients.
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Darbepoietin alpha ameliorates oxidative/nitrosative stress, decreases apoptosis, and improves clinical outcome in chronic canine monocytic ehrlichiosis
Abstract
Canine monocytic ehrlichiosis (CME) is an important hemoprotozoan disease of dogs associated with anemia, leucopenia, and thrombocytopenia. The present study was conducted with the aim of assessing the status of oxidative/nitrosative stress and apoptosis in naturally occurring cases of chronic canine monocytic ehrlichiosis, to investigate potential of darbepoietin alpha in ameliorating oxidative/nitrosative stress and apoptosis associated with CME and to assess the impact of darbepoietin alpha administration on clinical outcome in chronic canine monocytic ehrlichiosis. Thirty naturally occurring cases of chronic CME were allotted randomly in two treatment groups, groups I and II. Animals in group I were treated with doxycycline @10 mg/kg, PO, sid, for 28 days, and other supportive therapy. Whereas, animals in group II received darbapoietin alpha in addition to doxycycline and supportive therapy. Six apparently healthy dogs acted as healthy control. All these animals were monitored closely till 28 days of post treatment. Normocytic normochromic anemia, thrombocytopenia, decreased leukocyte count, increased levels of blood urea nitrogen (BUN), creatinine, alanine transaminase (ALT), and alkaline phosphatase (SAP) were observed in dogs suffering from chronic CME. There was significant increase in the levels of lipid peroxidation (LPO), nitric oxide (NO), and apoptosis percentage in dogs suffering from chronic CME. Levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase were significantly reduced in dogs suffering from chronic CME. Rapid improvement in the hematological values, oxidative, and nitrosative stress markers and percent apoptosis were observed in group II as compared to group I. Rapid clinical recovery and reduced hospital stay were observed in animals belonging to group II as compared to group I. No adverse effects of darbepoietin alpha administration were observed in the present study.
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Sleep-Wake Disorders in Stroke—Increased Stroke Risk and Deteriorated Recovery? An Evaluation on the Necessity for Prevention and Treatment
Abstract
Purpose of Review
Sleep-wake disorders (SWD) are common not only in the general population but also in stroke patients, in whom SWD may be pre-existent or appear "de novo" as a consequence of brain damage. Despite increasing evidence of a negative impact of SWD on cardiocerebrovascular risk, cognitive functions, and quality of life, SWD are insufficiently considered in the prevention and management of patients with stroke. This narrative review aims at summarizing the current data on the bidirectional link between SWD and stroke.
Recent Findings
Several studies have demonstrated that sleep-disordered breathing (SDB) is an independent risk factor for stroke and has a detrimental effect on stroke recovery. Short and long sleep duration and possibly other SWD (e.g., insomnia, circadian rhythm disorders) may also increase the risk of stroke and influence its outcome. Data on SDB treatment increasingly indicate a benefit on stroke risk and evolution while treatment of other SWD is still limited.
Summary
A systematic search for SWD in stroke patients is justified due to their high frequency and their negative impact on stroke outcomes. Clinicians should actively consider available treatment options.
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Unusual Techniques for Preserving Surgical and Oncologic Safety in Hepatectomy of Advanced Adrenal Malignancy with Vena Cava and Liver Invasion
Abstract
Background
Status in terms of major vascular structure invasion is a crucial factor for successful major hepatic resection. In particular, surgery for advanced tumors with inferior vena cava (IVC) invasion is difficult and may even be dangerous for the patient, having high risk of massive bleeding and greater chance of embolic complications such as stroke, bowel ischemia, and pulmonary venous thrombosis. For such reasons, many surgeons hesitate to carry out such surgical resection, and even if they do so, may not totally remove the tumor including the part inside the IVC, achieving R1 resection. For safe and radical surgery, various surgical techniques are required. We report herein three cases of major hepatectomy with IVC invasion and discuss several surgical tips.
Patients and Methods
From March 2011 to February 2014, we retrospectively reviewed three cases of adrenal malignancy with liver and IVC invasion. Based on the severity of the malignant tumor, each case illustrates a different method to address surgical complications and maintain oncologic safety. Case 1: A 34-year-old woman was diagnosed with adrenocortical tumor during medical examination. Tumor invaded the right lobe of the liver and very close to the IVC. Fortunately, there was little thrombosis inside the IVC; we performed right hemihepatectomy and adrenalectomy, then resected the IVC wall close to the tumor and repaired the IVC side wall using 4-0 Prolene. Case 2: A 54-year-old woman who complained of abdominal discomfort visited our hospital. Abdominal computed tomography (CT) scan revealed huge adrenal mass with liver and IVC invasion. Thrombosis inside the IVC extended to the right atrium. We decided to carry out veno-veno bypass during operation in collaboration with heart surgeon. After application of veno-veno bypass, the right atrium wall was opened and the tumor thrombus removed. We then carried out right hemihepatectomy and adrenalectomy. Supra- and infrahepatic vena cava were clamped during tumor thrombectomy to prevent embolic complications. Case 3: A 51-year-old woman who complained of headache and hypertension visited our hospital and was diagnosed with huge adrenal tumor. Tumor invaded to the right lobe of the liver and encased the IVC. The tumor totally invaded the IVC, and massive bleeding was expected during dissection. We resected the tumor including IVC en bloc, and reconstructed IVC with artificial graft (Dacron) under veno-veno bypass.
Results
In case 1, there was no surgical complication. The patient was discharged 7 days postoperatively and underwent adjuvant chemotherapy (Mitotane) after discharge. Unfortunately, multiple hepatic metastases were identified 4 months after operation. She died 6 months after surgery. In case 2, there was no surgical complication after surgery. The patient was discharged 10 days postoperatively. Multiple liver and lung metastases were identified 4 months after operation, and pulmonary embolism was also diagnosed on chemotherapy. She died 16 months after operation. In case 3, the patient had no surgical complication in the immediate postoperative period and was discharged 14 days after surgery. Pheochromocytoma was confirmed in pathologic report. One month after discharge, she underwent interventional balloon dilatation due to short segmental collapse of suprahepatic IVC. At 42 months after surgery, she was still alive with no relapse.
Discussion
In advanced-stage malignant tumor, the conflict between achieving oncologic R0 resection and patient safety remains an unsolved issue. In particular, more advanced surgical technique is required when the tumor invades large vessels such as the vena cava. Previous reports on cases of advanced tumor invading liver and IVC have described the technical difficulties.1,2 Wakayama et al. reported cases of successful thrombectomy under veno-veno bypass in hepatocellular carcinoma with IVC and right atrium invasion,3 and Vicente et al.4 reported surgical resection of IVC thrombus without cardiopulmonary bypass. Major vascular invasion of the tumor is known to be a poor prognostic factor for survival. However, some reports state that, if the tumor invades major vascular structure, complete tumor removal might be helpful for patient survival due to the biologic features of the tumor.2,5,6 This video report does not describe any new techniques, but is more helpful for junior surgeons in educational terms. The limitation of this report is that we could not show good oncologic long-term survival after surgery. However, no fatal complications related to the surgical procedure occurred, by managing the tumor thrombus during the operation. We present three techniques with differing aggressiveness. The techniques illustrated in this video represent a good option to achieve patient surgical safety.
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The Distal Predilection of Small Bowel Neuroendocrine Tumors
Abstract
Background
The small bowel (SB) is the most common site of neuroendocrine tumors (NETs) of the GI tract. These are described as being predominantly jejunoileal, but their exact locations within the SB have not been well defined. We sought to determine prospectively the spectrum of SBNET locations.
Methods
Patients undergoing exploration for SBNET primaries had measurement of bowel length, tumor locations, and resection length recorded. Correlations of clinicopathologic factors were performed, and analysis done utilizing Welch's t test, Chi square test, and the Kaplan–Meier method.
Results
Measurements were recorded in 123 patients, 107 of whom had complete information. Multifocal tumors (MTs) were found in 69 (56%) and unifocal (UTs) in 54 (44%) patients. Only 1 of 107 patients had a tumor within 100 cm of the ligament of Treitz (LT), whereas 77 of 107 (72%) had tumors within 100 cm of the ileocecal valve (ICV). No MTs were found within 100 cm of LT, whereas 41 of 60 (68%) patients had all (10) or at least one tumor (31) located within 100 cm of the ICV. MTs required a mean resection length of 108 versus 59 cm for UTs (p < 0.01). Seventy-seven percent of UTs (36/47) were within 100 cm of ICV. Tumors occurring only between > 100 cm from the LT and ICV were seen in 29 of 107 (27%) patients.
Conclusions
SBNETs are frequently multifocal and most commonly located within 100 cm of the ICV. SBNETs are less prevalent proximally in the small bowel, which may result from anatomic differences in enterochromaffin cell density, hormonal factors, or environmental exposures in the distal SB.
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Pharmacologic Properties of the Carrier Solutions for Hyperthermic Intraperitoneal Chemotherapy: Comparative Analyses Between Water and Lipid Carrier Solutions in the Rat Model
Abstract
Background
Carrier solutions play an important role in the distribution, plasma absorption, chemical stability, and solubility of anticancer agents during hyperthermic intraperitoneal chemotherapy (HIPEC). In the current study, lipophilic properties of carrier solutions were evaluated to determine whether they improved anticancer drug absorption rates using mitomycin-C (MMC) or oxaliplatin HIPEC as compared to hydrophilic carrier solutions.
Methods
Sprague-Dawley rats were divided into two groups: MMC and oxaliplatin treatment groups. Each group was then further subdivided by carrier solution: Dianeal® PD-2 peritoneal dialysis solution, 5% dextrose solution and 20% lipid solution (Lipision®). HIPEC was performed over 60 min at 41–42 °C using the anticancer drugs MMC (35 mg/m2) or oxaliplatin (460 mg/m2). The plasma area under the curve (AUC; AUCplasma), peritoneal AUC (AUCperitoneum), and peritoneal/plasma AUC ratios were compared among HIPEC carrier solutions.
Results
Plasma drug concentrations were significantly different among carrier solutions, varying by time. In contrast, peritoneal drug concentrations did not change with carrier solution. In the MMC group, the peritoneal/plasma AUC ratio of a lipid solution was three times higher than Dianeal® (p < 0.001). In the oxaliplatin group, the peritoneal/plasma AUC ratio was significantly different between carrier solutions (p = 0.046). Although the oxaliplatin AUCperitoneum did not vary (p = 0.941), the AUCplasma of a lipid solution was lower than that of 5% dextrose solution (p = 0.039).
Conclusions
The lipid carrier solution increases the peritoneal/plasma AUC ratio and decreases plasma absorption rates. However, further study is required before clinical uses, considering its pharmacologic properties and possible risks after HIPEC.
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Dose-Dependent Effect of Red Blood Cells Transfusion on Perioperative and Long-Term Outcomes in Peritoneal Surface Malignancies Treated with Cytoreduction and HIPEC
Abstract
Background
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are associated with increased red blood cell transfusion (RBT) demand. Although the deleterious effects of RBT are documented in various settings, its effect in this setting is obscure. In this study, we evaluated the effects of different-grade RBT on the short- and long-term outcomes of CRS and HIPEC.
Methods
We analyzed 231 patients with diffuse malignant peritoneal mesothelioma (DMPM) and 273 patients with pseudomyxoma peritonei (PMP) operated in our unit. RBT was categorized according to the amount of packed red blood cell units (PRBCs) administered (0, 1–2, 3–5, > 6). The effects of RBT on long-term oncological outcomes [progression-free survival (PFS) and overall survival (OS)] were assessed by using multivariate analysis.
Results
Overall, 74% of the patients were transfused with a median of 2 PRBCs (range 0–37). Transfusion level correlated with operative time, surgical extent (as measured by the peritoneal carcinomatosis index), and age. Postoperatively, patients with major transfusion (> 6 PRBCs) had increased mortality rate (11.1%, p = 0.01) and length of hospital stay (31.2 ± 16.8 days, p = 0.01) compared with other levels of RBT. RBT was dose-dependently associated with oncological outcomes in both DMPM and PMP for both PFS [hazard ratio (HR) = 1.40, 95% confidence interval (CI) 1.12–1.74, p = 0.003; HR = 1.44, 95% CI 1.15–1.81, p = 0.001, respectively] and OS (HR = 1.57, 95% CI 1.21–2.03, p = 0.001; HR = 1.43, 95% CI 1.15–1.90, p = 0.01, respectively).
Conclusions
Our data show a dose-dependent relationship between RBT and oncological outcomes. Further research to develop transfusion sparing protocols is needed in this extensive surgical procedure.
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Skeletal Muscle Attenuation (Sarcopenia) Predicts Reduced Overall Survival in Patients with Advanced Epithelial Ovarian Cancer Undergoing Primary Debulking Surgery
Abstract
Background
Sarcopenia was reported as a prognostic factor in cancer patients. Using computed tomography (CT), we analyzed the impact of sarcopenia on overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) after primary debulking surgery (PDS).
Methods
Preoperative CT scans of consecutive EOC patients (n = 323) were retrospectively assessed for skeletal muscle index (SMI) and muscle attenuation (MA; Hounsfield units [HU]). The optimal cut-off point for MA (32 HU) was calculated using the Martingale residuals method, and previously reported cut-offs for SMI were used. Logistic regression was used to determine univariate and multivariate factors associated with OS.
Results
Sarcopenia defined as SMI < 38.5, < 39, and 41 cm2/m2 was detected in 29.4, 33.7, and 47.1% of patients, respectively; however, none of these SMI cut-off levels were associated with OS. MA < 32 HU was present in 21.1% (68/323) of the total cohort. Significant differences between patients with MA < 32 and ≥ 32 HU were detected for median age (67 vs. 57 years), Eastern Cooperative Oncology Group (ECOG) > 0 (13.2 vs. 3.1%), comorbidity (age-adjusted Charlson Comorbidity Index [ACCI] ≥ 4; 36.8 vs. 13.3%), median body mass index (BMI; 27 vs. 24 kg/m2), International Federation of Gynecology and Obstetrics (FIGO) stage, histology (high-grade serous 95.6 vs. 84.7%), and complete resection (38.2 vs. 68.2%). MA < 32 HU remained a significant prognostic factor for OS in multivariate Cox regression analysis (hazard ratio 1.79, p = 0.003). Median OS in patients with MA < 32 HU versus MA ≥ 32 HU was 28 versus 56 months (p < 0.001). Furthermore, MA < 32 HU was significantly associated with OS in the prognostically poor population of patients with residual tumor (p = 0.015).
Conclusions
Low MA was significantly associated with poor survival, especially in patients with residual tumor after PDS. MA assessment could be used for risk stratification after PDS.
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Image-Guided Surgery in Patients with Pancreatic Cancer: First Results of a Clinical Trial Using SGM-101, a Novel Carcinoembryonic Antigen-Targeting, Near-Infrared Fluorescent Agent
Abstract
Background
Near-infrared (NIR) fluorescence is a promising novel imaging technique that can aid in intraoperative demarcation of pancreatic cancer (PDAC) and thus increase radical resection rates. This study investigated SGM-101, a novel, fluorescent-labeled anti-carcinoembryonic antigen (CEA) antibody. The phase 1 study aimed to assess the tolerability and feasibility of intraoperative fluorescence tumor imaging using SGM-101 in patients undergoing a surgical exploration for PDAC.
Methods
At least 48 h before undergoing surgery for PDAC, 12 patients were injected intravenously with 5, 7.5, or 10 mg of SGM-101. Tolerability assessments were performed at regular intervals after dosing. The surgical field was imaged using the Quest NIR imaging system. Concordance between fluorescence and tumor presence on histopathology was studied.
Results
In this study, SGM-101 specifically accumulated in CEA-expressing primary tumors and peritoneal and liver metastases, allowing real-time intraoperative fluorescence imaging. The mean tumor-to-background ratio (TBR) was 1.6 for primary tumors and 1.7 for metastatic lesions. One false-positive lesion was detected (CEA-expressing intraductal papillary mucinous neoplasm). False-negativity was seen twice as a consequence of overlying blood or tissue that blocked the fluorescent signal.
Conclusion
The use of a fluorescent-labeled anti-CEA antibody was safe and feasible for the intraoperative detection of both primary PDAC and metastases. These results warrant further research to determine the impact of this technique on clinical decision making and overall survival.
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Rheumatoid meningitis presenting with a stroke-like attack treated with recombinant tissue plasminogen activator: a case presentation
Rheumatoid meningitis presenting with a stroke-like attack (RMSA) is a rare manifestation of rheumatoid arthritis (RA). When the patients arrive within the time-window for recombinant tissue plasminogen activa...
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Efficacy of Sida pilosa Retz aqueous extract against Schistosoma mansoni – induced granulomatous inflammation in the liver and the intestine of mice: histomorphometry and gastrointestinal motility evaluation
The macerate of Sida pilosa aerial parts is used empirically for the treatment of intestinal helminthiasis. Previous studies have shown that Sida pilosa aqueous extract (SpAE) has schistosomicidal, antioxidant, a...
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Epigallocatechin gallate inhibits hepatitis B virus infection in human liver chimeric mice
Persistent hepatitis B virus (HBV) infection causes liver cirrhosis and hepatocellular carcinoma and constitutes a major worldwide health problem. Currently, anti-HBV drugs are limited to peginterferon and nuc...
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Chlorhexidine-coated surgical gloves influence the bacterial flora of hands over a period of 3 hours
The risk of SSI increases in the presence of foreign materials and may be caused by organisms with low pathogenicity, such as skin flora derived from hands of surgical team members in the event of a glove brea...
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DigitalMe: a journey towards personalized health and thriving
The use of information and communication technologies for health (eHealth) delivered via mobile-based or digitally enhanced solutions (mHealth) have rapidly evolved. When used together across various mobile ap...
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A Phase II and Biomarker Study of Sorafenib Combined with FOLFOX in Patients with Advanced Hepatocellular Carcinoma (HCC)
PURPOSE: Sorafenib is a standard first-line treatment for advanced HCC. The phase III SHARP trial showed a median time-to-progression(mTTP) of 5.5 months, overall response rate(ORR) of 2%, and median overall survival(mOS) of 10.7 months with sorafenib. FOLFOX4 has shown modest activity in advanced HCC. We evaluated the combination of sorafenib and modified (m)FOLFOX in a single-arm, multicenter phase II study. METHODS: The study included Child-Pugh A patients with advanced HCC and no prior systemic therapies. Patients received sorafenib 400mg BID for 2 weeks, followed by concurrent mFOLFOX (5-FUCI 1200mg/m2/day for 46 hours, leucovorin 200mg/m2 and oxaliplatin 85mg/m2 biweekly). The primary endpoint was mTTP with an alternative hypothesis of 7 months, and secondary endpoints included ORR, mOS, and circulating biomarkers. RESULTS: The study enrolled 40 patients: HCV/Etoh/HBV, 43%/28%/13%; Child-Pugh A5, 70%. Notable grade 3/4 adverse events included AST/ALT elevation(28%/15%), diarrhea(13%), hyperbilirubinemia(10%), hand-foot syndrome(8%), and bleeding(8%). mTTP was 7.7 months[95%CI: 4.4-8.9], ORR 18%, and mOS 15.1 months[7.9-16.9]. Sorafenib+mFOLFOX increased plasma PlGF, VEGF-D, sVEGFR1, IL-12p70 and CAIX and CD4+ and CD8+ effector T lymphocytes and decreased plasma sVEGFR2 and s-c-KIT and Tregs. Shorter TTP was associated with high baseline sVEGFR1. Shorter TTP and OS were associated with increases in Tregs and CD56Dim NK cells after sorafenib alone and plasma sMET after combination treatment (all p<0.05). CONCLUSIONS: Sorafenib+mFOLFOX met the pre-specified endpoint with encouraging efficacy but moderate hepatotoxicity. Thus, this regimen may be effective in select patients with adequate liver reserve. Biomarker evaluations suggested a correlation between TTP and angiogenic biomarkers and circulating Tregs.
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Dietary protein restriction reprograms tumor associated macrophages and enhances immunotherapy
Purpose: Diet and healthy weight are established means of reducing cancer incidence and mortality. However, the impact of diet modifications on the tumor microenvironment (TME) and antitumor immunity are not well-defined. Immunosuppressive tumor-associated macrophages (TAMs) are associated with poor clinical outcomes and are potentially modifiable through dietary interventions. We tested the hypothesis that dietary protein restriction modifies macrophage function toward antitumor phenotypes. Experimental design: Macrophage functional status under different tissue culture conditions and in vivo was assessed by Western blot, immunofluorescence, qRT-PCR, and cytokine array analyses. Tumor growth in the context of protein or amino acid (AA)-restriction and immunotherapy, namely a survivin peptide-based vaccine or a PD-1 inhibitor, was examined in animal models of prostate (RP-B6Myc) and renal (RENCA) cell carcinoma. All tests were two-sided. Results: Protein or AA-restricted macrophages exhibited enhanced tumoricidal, pro-inflammatory phenotypes, and in two syngeneic tumor models, protein or AA-restricted diets elicited reduced TAM infiltration, tumor growth, and increased response to immunotherapies. Further, we identified a distinct molecular mechanism by which AA-restriction reprograms macrophage function via a ROS/mTOR centric cascade. Conclusions: Dietary protein restriction alters TAM activity and enhances the tumoricidal capacity of this critical innate immune cell type, providing the rationale for clinical testing of this supportive tool in patients receiving cancer immunotherapies.
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Clinical Pharmacology of Tisagenlecleucel in B-Cell Acute Lymphoblastic Leukemia
Purpose: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Experimental Design: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across 2 studies in pediatric B-ALL (ELIANA; ENSIGN). Results: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (n = 62) had 2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders (n = 7; 73.5% and 104% higher geometric mean Cmax and AUC0-28d, respectively) with persistence measurable beyond 2 years in responding patients. Cmax increased with occurrence and severity of cytokine release syndrome (CRS) and neurological events. Tisagenlecleucel continued to expand and persist following tocilizumab, used to manage CRS. Patients with B cell recovery within 6 months had earlier loss of the transgene compared with patients with sustained clinical response. Clinical responses were seen across the entire dose range evaluated (patients ≤50 kg: 0.2 to 5.0 x 106/kg; patients >50 kg: 0.1 to 2.5 x 108 CAR positive viable T cells) with no relationship between dose and safety. Neither preexisting nor treatment-induced anti-murine CAR19 antibodies impacted the persistence or clinical response. Conclusions: Response to tisagenlecleucel was associated with increased expansion across a wide dose range. These results highlight the importance of cellular kinetics in understanding determinants of response to chimeric antigen receptor T-cell therapy.
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Structural Variants and Selective Sweep Foci Contribute to Insecticide Resistance in the Drosophila Genetic Reference Panel
Patterns of nucleotide polymorphism within populations of Drosophila melanogaster suggest that insecticides have been the selective agents driving the strongest recent bouts of positive selection. However, there is a need to explicitly link selective sweeps to the particular insecticide phenotypes that could plausibly account for the drastic selective responses that are observed in these non-target insects. Here, we screen the Drosophila Genetic Reference Panel with two common insecticides; malathion (an organophosphate) and permethrin (a pyrethroid). Genome-wide association studies map survival on malathion to the two of the largest sweeps in the D. melanogaster genome; Ace and Cyp6g1. Malathion survivorship also correlates with lines which have high levels of Cyp12d1, Jheh1 and Jheh2 transcript abundance. Permethrin phenotypes map to the largest cluster of P450 genes in the Drosophila genome, however in contrast to a selective sweep driven by insecticide use, the derived allele seems to be associated with susceptibility. These results underscore previous findings that highlight the importance of structural variation to insecticide phenotypes: Cyp6g1 exhibits copy number variation and transposable element insertions, Cyp12d1 is tandemly duplicated, the Jheh loci are associated with a Bari1 transposable element insertion, and a Cyp6a17 deletion is associated with susceptibility
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Signatures of Insecticide Selection in the Genome of Drosophila melanogaster
Resistance to insecticides has evolved in multiple insect species, leading to increased application rates and even control failures. Understanding the genetic basis of insecticide resistance is fundamental for mitigating its impact on crop production and disease control. We performed a GWAS approach with the Drosophila Genetic Reference Panel (DGRP) to identify the mutations involved in resistance to two widely used classes of insecticides: organophosphates (OPs, parathion) and pyrethroids (deltamethrin). Most variation in parathion resistance was associated with mutations in the target gene Ace, while most variation in deltamethrin resistance was associated with mutations in Cyp6a23, a gene encoding a detoxification enzyme never previously associated with resistance. A "nested GWAS" further revealed the contribution of other loci: Dscam1 and trpl were implicated in resistance to parathion, but only in lines lacking Wolbachia. Cyp6a17, the paralogous gene of Cyp6a23, and CG7627, an ATP-binding cassette transporter, were implicated in deltamethrin resistance. We observed signatures of recent selective sweeps at all of these resistance loci and confirmed that the soft sweep at Ace is indeed driven by the identified resistance mutations. Analysis of allele frequencies in additional population samples revealed that most resistance mutations are segregating across the globe, but that frequencies can vary substantially among populations. Altogether, our data reveal that the widely used OP and pyrethroid insecticides imposed a strong selection pressure on natural insect populations. However, it remains unclear why, in Drosophila, resistance evolved due to changes in the target site for OPs, but due to a detoxification enzyme for pyrethroids.
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Beaumont Bio Med, Inc. Issues Voluntary Nationwide Recall of all their Homeopathic Aqueous/Alcohol-Based Medicines due to the Nationwide Recall by the Contract Manufacturer, King Bio, of all their Aqueous-Based Products due to Possible Microbial Contamination
Audience: Consumer, Health Professional, Pharmacy Beaumont Bio Med, Inc. is voluntarily recalling its entire aqueous/alcohol-based product line for human use, within expiry, to the consumer level. All products manufactured by the contract...
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Hospitals Using Two Strategies to Up Quality, Lower Costs
THURSDAY, Sept. 6, 2018 -- Hospitals receiving bundled payments are reducing skilled nursing facility (SNF) use and improving care integration to improve quality and control costs, according to a report published in the August issue of Health...
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Better Training Needed to Boost LGBTQ Patient Health Care
THURSDAY, Sept. 6, 2018 -- High-quality health care needs to be provided to lesbian, gay, bisexual, transgender, and queer (LGBTQ) patients, and improved training is necessary to deliver that care, according to a report published in the American...
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Hospital Groups Launch Own Generic Drug Company
THURSDAY, Sept. 6, 2018 -- Three U.S. health care foundations and seven hospital groups have formed a generic drug company to combat high prices and chronic shortages of medicines. The company, Civica Rx, will start with 14 widely used hospital...
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Goop Reaches Settlement in False Advertising Lawsuit
THURSDAY, Sept. 6, 2018 -- A $145,000 settlement will be paid by actress Gwyneth Paltrow's company, Goop, in a lawsuit over unfounded claims that some of its products improve women's sexual and emotional health. The lawsuit was filed by prosecutors...
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Opioid Maker to Pay for Overdose Antidote Development
THURSDAY, Sept. 6, 2018 -- A $3.4 million grant to help a non-profit company develop a less expensive opioid overdose antidote was announced by Purdue Pharma, which makes the opioid painkiller OxyContin. The grant is being given to Pittsburgh-based...
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Beaumont Bio Med, Inc. Issues Voluntary Nationwide Recall of all their Homeopathic Aqueous/Alcohol-Based Medicines due to the Nationwide Recall by the Contract Manufacturer, King Bio, of all their Aqueous-Based Products due to Possible Microbial Contamination
Audience: Consumer, Health Professional, Pharmacy Beaumont Bio Med, Inc. is voluntarily recalling its entire aqueous/alcohol-based product line for human use, within expiry, to the consumer level. All products manufactured by the contract...
https://ift.tt/2QbcJ21
The Emergency Department Diagnosis and Management of Urinary Tract Infection
Urinary tract infection (UTI) is a common infection seen in the emergency department. The spectrum of UTI includes simple versus complicated infection and lower versus upper UTI. No one history or examination finding is definitive for diagnosis. Testing often includes urinalysis and/or urine dipstick, and several pitfalls may occur in interpretation. Urine cultures should be obtained in complicated or upper UTIs but not simple and lower tract UTIs, unless a patient is pregnant. Imaging often is not required. Most patients with simple cystitis and pyelonephritis are treated as outpatients. A variety of potentially dangerous conditions may mimic UTI and pyelonephritis.
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Management of Patients with Sexually Transmitted Infections in the Emergency Department
Sexually transmitted infections (STI) are very common infections in the United States. Most patients with STIs are evaluated and treated in primary care settings; however, many also present to the Emergency Department (ED) for initial care. Management of STIs in the ED includes appropriate testing and treatment per CDC Sexually Transmitted Diseases Treatment Guidelines. Although most patients with STIs are asymptomatic or may only exhibit mild symptoms, serious complications from untreated infection are possible. Pregnant women with STIs are particularly vulnerable to serious complications; therefore, empiric ED treatment combined with close follow-up care and referral to obstetrics are paramount.
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Antimicrobial Stewardship in the Emergency Department
The emergency department (ED) is the hub of the US health care system. Acute infectious diseases are frequently encountered in the ED setting, making this a critical setting for antimicrobial stewardship efforts. Systems level and behavioral stewardship interventions have demonstrated success in the ED setting but successful implementation depends on institutional support and the presence of a physician champion. Antimicrobial stewardship efforts in the ED should target high-impact areas: antibiotic prescribing for nonindicated respiratory tract conditions, such as bronchitis and sinusitis; overtreatment of asymptomatic bacteriuria; and using two antibiotics (double coverage) for uncomplicated cases of cellulitis or abscess.
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Management of Human Immunodeficiency Virus in the Emergency Department
Over the past 30 years, significant advances have transformed the landscape of human immunodeficiency virus (HIV) care in the emergency department. Diagnosis and management of HIV has improved, resulting in a decline in the incidence of acquired immunodeficiency syndrome (AIDS)-defining infections. Advances in pharmacology have led to fewer serious medication toxicities and more tolerable regimens. Emergency providers have played an increasingly important role in HIV screening and diagnosis of acute infection. Provision of postexposure prophylaxis is expanding from a focus on occupational exposure to include all high-risk cases.
https://ift.tt/2Q5N5f8
Infectious Disease Emergencies in Oncology Patients
Oncology patients are a unique patient population in the emergency department (ED). Malignancy and associated surgical, chemotherapeutic, or radiation therapies put them at an increased risk for infection. The most ominous development is neutropenic fever, which happens often and may not present with signs or symptoms other than fever. A broad differential diagnosis is essential when considering infectious disease pathology in both neutropenic and non-neutropenic oncology patients in the ED.
https://ift.tt/2NUIE5g
Infectious Diseases After Hydrologic Disasters
Hydrologic disasters, including hurricanes, tsunamis, and severe flooding, have been associated with infectious diseases, particularly among vulnerable and displaced populations in resource-poor settings. Skin and soft tissue infections, gastrointestinal infections, respiratory infections, zoonotic infections, and vector-borne diseases each present unique threats to human health in this setting. Increased emergency physician awareness of these infectious diseases and their diagnosis and management helps optimize medical care for survivors after a hydrologic disaster and safeguard the health of disaster responders.
https://ift.tt/2Qc1arF
Musculoskeletal Infections in the Emergency Department
Bone and joint infections are potentially limb-threatening or even life-threatening diseases. Emergency physicians must consider infection when evaluating musculoskeletal complaints, as misdiagnosis can have significant consequences. Patients with bone and joint infections can have heterogeneous presentations with nonspecific signs and symptoms. Staphylococcus aureus is the most commonly implicated microorganism. Although diagnosis may be suggested by physical examination, laboratory testing, and imaging, tissue sampling for Gram stain and microbiologic culture is preferable, as pathogen identification and susceptibility testing help optimize long-term antibiotic therapy. A combination of medical and surgical interventions is often necessary to effectively manage these challenging infections.
https://ift.tt/2NUWKnm
Protecting Our Nutrient Safety Net
Food insecurity, part of the complex matrix of poverty and toxic stress, is a significant health risk. Embarrassingly, the US ranks among the highest of the developed countries in the prevalence of food insecurity, with the prevalence of food insecurity higher than Canada, Australia, Germany, France, Denmark, Spain, and the United Kingdom.1 In 2016, 16.5% of US households with children reported food insecurity2; that is, 4.2 million households were unable to provide adequate food for their children.
https://ift.tt/2NUTWGQ
Maternal Lifetime Trauma and Birthweight: Effect Modification by In Utero Cortisol and Child Sex
To evaluate associations between maternal lifetime traumatic stress and offspring birthweight and examine modifying effects of third trimester cortisol and fetal sex.
https://ift.tt/2wS2eYC
Early Postnatal Ventricular Dysfunction Is Associated with Disease Severity in Patients with Congenital Diaphragmatic Hernia
To assess patterns of postnatal ventricular function and their relationship to prenatal and postnatal markers of disease severity in infants with congenital diaphragmatic hernia (CDH).
https://ift.tt/2NlF3Ak
Early Glycemic Profile Is Associated with Brain Injury Patterns on Magnetic Resonance Imaging in Hypoxic Ischemic Encephalopathy
To investigate whether the early glycemic profile in infants with hypoxic ischemic encephalopathy is associated with distinct patterns of brain injury on magnetic resonance imaging (MRI).
https://ift.tt/2MSVe8F
Risk of Bacterial Coinfections in Febrile Infants 60 Days Old and Younger with Documented Viral Infections
To determine the risk of serious bacterial infections (SBIs) in young febrile infants with and without viral infections.
https://ift.tt/2MSVgNP
Polaris® expands its public safety line to include all-electric GEM® vehicles
MINNEAPOLIS — Polaris® Government and Defense is adding all-electric GEM® vehicles to its line of highly mobile, affordable, and professional public safety vehicles. Polaris firefighting, law enforcement, and rescue RANGER® and GENERAL® vehicles are proven effective and can go places cars, trucks, helicopters, and other alternatives can't. Now,...
https://ift.tt/2NUgJ5H
The Emergency Department Diagnosis and Management of Urinary Tract Infection
Urinary tract infection (UTI) is a common infection seen in the emergency department. The spectrum of UTI includes simple versus complicated infection and lower versus upper UTI. No one history or examination finding is definitive for diagnosis. Testing often includes urinalysis and/or urine dipstick, and several pitfalls may occur in interpretation. Urine cultures should be obtained in complicated or upper UTIs but not simple and lower tract UTIs, unless a patient is pregnant. Imaging often is not required. Most patients with simple cystitis and pyelonephritis are treated as outpatients. A variety of potentially dangerous conditions may mimic UTI and pyelonephritis.
https://ift.tt/2NUX2KY
Management of Patients with Sexually Transmitted Infections in the Emergency Department
Sexually transmitted infections (STI) are very common infections in the United States. Most patients with STIs are evaluated and treated in primary care settings; however, many also present to the Emergency Department (ED) for initial care. Management of STIs in the ED includes appropriate testing and treatment per CDC Sexually Transmitted Diseases Treatment Guidelines. Although most patients with STIs are asymptomatic or may only exhibit mild symptoms, serious complications from untreated infection are possible. Pregnant women with STIs are particularly vulnerable to serious complications; therefore, empiric ED treatment combined with close follow-up care and referral to obstetrics are paramount.
https://ift.tt/2Q8YHy1
Antimicrobial Stewardship in the Emergency Department
The emergency department (ED) is the hub of the US health care system. Acute infectious diseases are frequently encountered in the ED setting, making this a critical setting for antimicrobial stewardship efforts. Systems level and behavioral stewardship interventions have demonstrated success in the ED setting but successful implementation depends on institutional support and the presence of a physician champion. Antimicrobial stewardship efforts in the ED should target high-impact areas: antibiotic prescribing for nonindicated respiratory tract conditions, such as bronchitis and sinusitis; overtreatment of asymptomatic bacteriuria; and using two antibiotics (double coverage) for uncomplicated cases of cellulitis or abscess.
https://ift.tt/2M2EI0B
Management of Human Immunodeficiency Virus in the Emergency Department
Over the past 30 years, significant advances have transformed the landscape of human immunodeficiency virus (HIV) care in the emergency department. Diagnosis and management of HIV has improved, resulting in a decline in the incidence of acquired immunodeficiency syndrome (AIDS)-defining infections. Advances in pharmacology have led to fewer serious medication toxicities and more tolerable regimens. Emergency providers have played an increasingly important role in HIV screening and diagnosis of acute infection. Provision of postexposure prophylaxis is expanding from a focus on occupational exposure to include all high-risk cases.
https://ift.tt/2Q5N5f8
Infectious Disease Emergencies in Oncology Patients
Oncology patients are a unique patient population in the emergency department (ED). Malignancy and associated surgical, chemotherapeutic, or radiation therapies put them at an increased risk for infection. The most ominous development is neutropenic fever, which happens often and may not present with signs or symptoms other than fever. A broad differential diagnosis is essential when considering infectious disease pathology in both neutropenic and non-neutropenic oncology patients in the ED.
https://ift.tt/2NUIE5g
Infectious Diseases After Hydrologic Disasters
Hydrologic disasters, including hurricanes, tsunamis, and severe flooding, have been associated with infectious diseases, particularly among vulnerable and displaced populations in resource-poor settings. Skin and soft tissue infections, gastrointestinal infections, respiratory infections, zoonotic infections, and vector-borne diseases each present unique threats to human health in this setting. Increased emergency physician awareness of these infectious diseases and their diagnosis and management helps optimize medical care for survivors after a hydrologic disaster and safeguard the health of disaster responders.
https://ift.tt/2Qc1arF
Musculoskeletal Infections in the Emergency Department
Bone and joint infections are potentially limb-threatening or even life-threatening diseases. Emergency physicians must consider infection when evaluating musculoskeletal complaints, as misdiagnosis can have significant consequences. Patients with bone and joint infections can have heterogeneous presentations with nonspecific signs and symptoms. Staphylococcus aureus is the most commonly implicated microorganism. Although diagnosis may be suggested by physical examination, laboratory testing, and imaging, tissue sampling for Gram stain and microbiologic culture is preferable, as pathogen identification and susceptibility testing help optimize long-term antibiotic therapy. A combination of medical and surgical interventions is often necessary to effectively manage these challenging infections.
https://ift.tt/2NUWKnm
Mebendazole potentiates radiation therapy in triple-negative breast cancer
Triple-negative breast cancer (TNBC) remains one of the most challenging breast cancers to treat, despite aggressive treatment approaches including radiation therapy. In this study, a common antihelminthic drug, mebendazole (MBZ) is shown to deplete breast cancer stem cells in a TNBC model and act as a potent radiosensitizer in vitro and in vivo. These results strongly support the repurposing of MBZ as a radiosensitizer for the treatment of TNBC patients in combination with radiation therapy.
https://ift.tt/2oLGM3T
Periodic Limb Movements in Sleep: Prevalence and Associated Sleepiness in the Wisconsin Sleep Cohort
Periodic limb movements in sleep (PLMS)1 are repetitive bursts of muscle activity, typically in the lower limbs, which may be accompanied by an arousal or sleep fragmentation(Pollmacher et al., 1993). Although PLMS are believed to increase with age(Ancoli-Israel et al., 1985, Ferri et al., 2008), until recently, the prevalence of PLMS in the general population had not been reliably estimated. Small studies have reported prevalence rates between 5 and 11%(Hornyak et al., 2006, Scofield et al., 2008), including a community-based sample of 592 participants recruited from the general population of tri-country Detroit which reported 7.6% (Hornyak et al., 2006, Scofield et al., 2008).
https://ift.tt/2Q74ZhP
EEG coherence in a mental arithmetic task performance in first episode schizophrenia and schizoaffective disorder
Current theories of schizophrenia (SZ) have emphasized that the pathophysiology arises from a 'dysconnectivity' between and within cortical areas of the brain (Friston, 1999, Uhlhaas and Singer, 2010, Stephan et al., 2009). Studies of functional connectivity in patients with schizophrenia using PET and functional MRI data both during cognitive tasks (Potkin and Ford, 2009 for a review) and at rest (for a review see Greicius, 2008) vastly support this hypothesis. However, less attention has been paid to the particular disorders within the schizophrenia spectrum.
https://ift.tt/2CA73fA
The utility and application of electrophysiological methods in the study of visual hallucinations
Visual hallucinations (VH) are a common symptom in both clinical and non-clinical populations, including a wide range of psychiatric, neurological, and ophthalmologic conditions such as schizophrenia, neurodegenerative dementias, eye disease, delirium and drug-induced hallucinosis (Abraham and Duffy 1996; Menon et al. 2003; Collerton et al. 2005; Armstrong (2012); ffytche and Wible 2014).
https://ift.tt/2Q74Nz7
Atypical perceptual and neural processing of emotional prosodic changes in children with Autism Spectrum Disorders
Deficient social communication skills, narrow interests, and repetitive behavior are the main diagnostic features of autism spectrum disorders (ASD) (APA, 2013). Some individuals with ASD show significant delays and abnormalities in their language development (later referred to as children with ASD (LI) in this article), whereas some individuals with ASD show rather typical formal language development (later referred to as children with ASD (no LI)) (WHO, 1993; Rapin and Dunn, 2003; Gillberg and Coleman, 2000).
https://ift.tt/2CqJCVH
Influence of Early Life, Diet, and the Environment on the Microbiome
Advances in sequencing technology and bioinformatics have greatly enhanced our ability to understand the human microbiome. Over the last decade, a growing body of literature has linked nutrition and the environment to the microbiome and is now thought to be an important contributor to overall health. This paper reviews the literature from the past 10 years to highlight the influence of environmental factors such as diet, early life adversity and stress in shaping and modifying our microbiome towards health and disease.
https://ift.tt/2Qb6WcN
Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function
The gut microbiome, a diverse microbial community in the gastrointestinal tract, plays a pivotal role in the maintenance of health. The gut microbiome metabolizes dietary and host-derived molecules to produce bioactive metabolites, which have a wide array of effects on host metabolism and immunity. 'Dysbiosis' of the gut microbiome, commonly considered as perturbation of microbiome diversity and composition, has been associated with intestinal and extra-intestinal diseases, including nonalcoholic fatty liver disease (NAFLD).
https://ift.tt/2M7iAlK
Range of Normal Liver stiffness and Predictors of Suspected Advanced Fibrosis in Apparently Healthy Individuals: A Pooled Analysis of 16,082 Participants
Transient elastography (TE) is a noninvasive technique that measures liver stiffness (LSM) as a surrogate of fibrosis severity. LSM range in healthy and susceptible individuals is unclear. We aim to define the range of LSM in healthy individuals, delineating the impact of metabolic abnormalities on LSM.
https://ift.tt/2M5qPPl
Low Prevalence of Suspected Barrett’s Esophagus in Gastroesophageal Reflux Disease Without Alarm Symptoms
Esophagogastroduodenoscopy (EGD) is frequently used to evaluate gastroesophageal reflux disease (GERD) without alarm symptoms, although the benefits are not clear. We aimed determine the prevalence of uncomplicated GERD as an indication for EGD, the demographic characteristics of these patients, and the endoscopic outcomes of these procedures.
https://ift.tt/2NUSZ1e
Pulsara adds key communication features to its healthcare mobile platform
Pulsara is proud to announce the release of two new ingenious elements of its application, Video Chat and Audio Clips, that will enable clinicians to communicate in a much broader way. 2018 has shown to be a breakthrough year for this company with a number of major feature releases, including the recent Consult/Transfer component. These features further enhance regional communication amongst...
https://ift.tt/2CD2elJ
Delivery Assist Catheters
Abstract
Purpose
To report in vivo experience of a delivery assist catheter as ascending aid for a large-bore catheter for intracranial thromboaspiration.
Methods
Retrospective data collection and analysis of stroke databases of two comprehensive stroke centers focusing on technical and angiographic parameters – primary endpoint defined as reaching the occlusion with a large-bore reperfusion catheter – from patients receiving endovascular stroke treatment using an AXS Offset™ delivery assist catheter (Stryker, Fremont, CA, USA) between May 2017 and November 2017.
Results
Using the delivery assist catheter, a 6F catheter could be advanced to an intracranial occlusion for direct thromboaspiration in 30 (88.2%) out of a total of 34 patients (male: n = 14 out of 34 [41.2%], age in years: mean [SD]: 75 [11], median baseline NIHSS [National Institutes of Health stroke scale]: 16 [interquartile range, IQR 12-21]). In 4 out of 34 (11.7%) cases the occlusion could not be reached with the aspiration catheter because of a preceding non-occlusive arteriosclerotic plaque (n = 1, 2.9%) or because of severe elongation and tortuosity of the arterial access route (n = 3, 8.8%). After thromboaspiration mTICI (modified thrombolysis in cerebral infarction) 2b‑3 was reached in 14 out of 30 (46.7%) patients. In 21 out of 34 (61.8%) patients stent-retriever-maneuvers (median: 1 [IQR: 0‑2]) were needed. In 28 out of 34 (82.3%) patients final mTICI 2b-3 could be achieved.
Conclusion
Delivery assist catheters can be used as ascending aid for large-bore catheters for thromboaspiration in acute ischemic stroke, in particular to overcome vessel tortuosity and anatomic obstacles.
https://ift.tt/2NQ4Tcx
Does the King Airway system signal the end of intubation skills?
Our co-hosts tackle the topic of supraglottic airways, and the best way to approach them in the field
https://ift.tt/CyMyi5
Engineering Transplantation-suitable Retinal Pigment Epithelium Tissue Derived from Human Embryonic Stem Cells
We describe a method to engineer a retinal tissue composed of retinal pigment epithelial cells derived from human pluripotent stem cells cultured on top of human amniotic membranes and its preparation for grafting in animal models.
https://ift.tt/2M58dyN
Widespread Statin Use Not Recommended in Old, Very Old
THURSDAY, Sept. 6, 2018 -- Statin use is not associated with reduced risk of atherosclerotic cardiovascular disease (CVD) or all-cause mortality among older adults without type 2 diabetes, according to a study published online Sept. 5 in The...
https://ift.tt/2oMeh6r
Physical Activity Not Linked to Natural Early Menopause
THURSDAY, Sept. 6, 2018 -- Physical activity is not associated with natural menopause before age 45 years (early menopause), according to a study published online Aug. 21 in Human Reproduction. Mingfei Zhao, M.P.H., from the University of...
https://ift.tt/2Cq3RTB
Psychological Distress Linked to Increased Risk of MI, Stroke
THURSDAY, Sept. 6, 2018 -- Psychological distress is associated with myocardial infarction (MI) and stroke in men and women, according to a study published online Aug. 28 in Circulation: Cardiovascular Quality and Outcomes. Caroline A. Jackson,...
https://ift.tt/2Cq3OqT
Chronic Vaping Exerts Biological Effects on Lung
THURSDAY, Sept. 6, 2018 -- Chronic vaping exerts biological effects on the lung, some of which are mediated by the propylene glycol/vegetable glycerin (PG/VG) base, according to a study published recently in the American Journal of Respiratory and...
https://ift.tt/2wNbZsa
PSA Testing Not Recommended for Prostate Cancer Screening
THURSDAY, Sept. 6, 2018 -- Prostate cancer screening with prostate-specific antigen (PSA) testing is not recommended, although certain groups of men are more likely to undergo testing, according to a review and recommendations published online Sept....
https://ift.tt/2Cq3KHF
Increase Observed in Hearts From Drug-Intoxicated Donors
THURSDAY, Sept. 6, 2018 -- Heart transplants using drug-intoxicated donors have significantly increased, but their use does not seem to adversely impact post-transplant survival, according to a study recently published in the American Journal of...
https://ift.tt/2oMe6bh
Perinatal Mortality Rates Remain Unchanged From 2014 to 2016
THURSDAY, Sept. 6, 2018 -- Rates of perinatal mortality remained unchanged from 2014 to 2016, according to an August data brief published by the U.S. Centers for Disease Control and Prevention's National Center for Health Statistics. Elizabeth C.W....
https://ift.tt/2wOPbrJ
Publication Characteristics Tied to Treatment Effects
THURSDAY, Sept. 6, 2018 -- Published trials have larger treatment effects than unpublished trials, while trials published in a language other than English have larger treatment effects versus those published in English, according to research...
https://ift.tt/2Co2swA
Does the King Airway system signal the end of intubation skills?
Our co-hosts tackle the topic of supraglottic airways, and the best way to approach them in the field
https://ift.tt/EnXn36
Tackling Loneliness
Most of us would not consider loneliness a public health epidemic, yet startling new findings show that a majority of Americans are lonely – according to a survey that Cigna conducted with 20,000 Americans – and loneliness is at the heart of physical and mental health. Not only did our new study find that most Americans are considered lonely, but those who are lonely are much more...
https://ift.tt/2wN0LUw
A Tissue Culture Model of Estrogen-producing Primary Bovine Granulosa Cells
A long-term culture model of bovine granulosa cells under serum-free conditions is described. This model allows researchers to study the effects of diverse factors and conditions as different plating densities on the characteristics of estrogen-producing bovine granulosa cells.
https://ift.tt/2QbIN6e
What Anglo Saxon teeth can tell us about modern health
https://ift.tt/2Nk4d2k
Defined Xeno-free and Feeder-free Culture Conditions for the Generation of Human iPSC-derived Retinal Cell Models
The production of specialized retinal cells from pluripotent stem cells is a turning point in the development of stem cell-based therapy for retinal diseases. The present paper describes a simple method for an efficient generation of retinal organoids and retinal pigmented epithelium for basic, translational, and clinical research.
https://ift.tt/2NTvvJR
Assessment of Methane and Nitrous Oxide Fluxes from Paddy Field by Means of Static Closed Chambers Maintaining Plants Within Headspace
The overall goal of this protocol is to measure greenhouse gas emissions from paddy fields using the static closed chamber technique. The measurement system needs specific adjustments due to the presence of both a permanent water layer in the field and of the plants within the chamber headspace.
https://ift.tt/2MVCq8O
The effect of comorbidities on outcomes in colorectal cancer survivors: a population-based cohort study
Abstract
Purpose
To examine the prevalence of comorbidities and the association of these comorbidities with demographics, tumor characteristics, treatments received, overall survival, and causes of death in a population-based cohort of colorectal cancer (CRC) patients.
Methods
Adult patients with stage I–III CRC diagnosed between 2004 and 2015 were included. Comorbidities were captured using Charlson comorbidity index. Causes of death were categorized using International Classification of Diseases, tenth revision codes. Patients were categorized into five mutually exclusive comorbid groups (cardiovascular disease alone, diabetes alone, cardiovascular disease plus diabetes, other comorbidities, or no comorbidities). Data were analyzed using descriptive statistics, Kaplan-Meier survival analyses, and Cox proportional hazards models.
Results
There were 12,265 patients. Mean follow-up was 3.8 years. Approximately one third of patients had a least one comorbidity, with cardiovascular disease and diabetes being most common. There were statistically significant differences across comorbid groups on treatments received and overall survival. Those with comorbidity had lower odds of treatment and greater risk of death than those with no comorbidity. Those with cardiovascular disease plus diabetes fared the worst for prognosis (median overall survival 3.3 [2.8–3.7] years; adjusted HR for death, 2.27, 95% CI 2.0–2.6, p < .001). Cardiovascular disease was the most common cause of non-CRC death.
Conclusions
CRC patients with comorbidity received curative intent treatment less frequently and experienced worse outcomes than patients with no comorbidity. Cardiovascular disease was the most common cause of non-cancer death.
Implications for Cancer Survivors
Management of comorbidities, including healthy lifestyle coaching, at diagnosis and into survivorship is an important component of cancer care.
https://ift.tt/2NouqwB
Trends in Breast Cancer Mortality by Stage at Diagnosis Among Young Women in the United States
Cancer, EarlyView.
https://ift.tt/2M5je3g
"Precision" Public Health — Between Novelty and Hype
In May 2018, the National Institutes of Health (NIH) began enrollment for a vast medical research cohort. Named "All of Us," it's meant to include 1 million U.S. volunteers, who will be studied over 10 years at a cost of $1.45 billion. The project promises to "lay the scientific foundation for a…
https://ift.tt/2MVojAr
Medicare Spending after 3 Years of the Medicare Shared Savings Program
https://ift.tt/2CpnKKf
MR Thermography-Guided Head and Neck Lesion Laser Ablation [HEAD & NECK]
SUMMARY:
Interstitial laser ablation has been successfully used as a minimally invasive treatment option for tumors in many parts of the body, including the head and neck. In this article, we describe the use of MR imaging guidance and mapping sequences for accurate localization of the target lesion, percutaneous interstitial laser ablation methods, and the use of MR thermography for temperature monitoring during laser ablation, with a focus on applications in the head and neck region.
https://ift.tt/2wMIC9o
Management of challenging immune-related gastrointestinal adverse events associated with immune checkpoint inhibitors
Future Oncology, Ahead of Print.
https://ift.tt/2wLAftL
Brachial Plexus Ultrasound and MRI in Children with Brachial Plexus Birth Injury [PEDIATRICS]
BACKGROUND AND PURPOSE:
Brachial plexus birth injury is caused by traction on the neck during delivery and results in flaccid palsy of an upper extremity commonly involving C5–C6 nerve roots. MR imaging and MR myelography help to assess the anatomic location, extent, and severity of brachial plexus injuries which influence the long-term prognosis along with the surgical decision making. Recently, sonography has been increasingly used as the imaging modality of choice for brachial plexus injuries. The aim of this study was to assess the degree of correlation among brachial plexus sonography, MR imaging, and surgical findings in children with brachial plexus birth injury.
MATERIALS AND METHODS:This prospective study included 55 consecutive patients (girls/boys = 32:23; mean age, 2.1 ± 0.8 months) with brachial plexus birth injury between May 2014 and April 2017. The patients were classified according to the Narakas classification and were followed up at 4- to 6-week intervals for recovery by the Modified Mallet system and sonography without specific preparation for evaluation. All patients had MR imaging under general anesthesia. Nerve root avulsion-retraction, pseudomeningocele, and periscalene soft tissue were accepted brachial plexus injury findings on imaging. Interobserver agreement for MR imaging and the agreement between imaging and surgical findings were estimated using the statistic. The diagnostic accuracy of sonography and MR imaging was calculated on the basis of the standard reference, which was the surgical findings.
RESULTS:Forty-three patients had pre- and postganglionic injury, 12 had only postganglionic injury findings, and 47% of patients underwent an operation. On sonography, no patients had preganglionic injury, but all patients had postganglionic injury findings. For postganglionic injury, the concordance rates between imaging and the surgical findings ranged from 84% to 100%, and the diagnostic accuracy of sonography and MR imaging was 89% and 100%, respectively. For preganglionic injury, the diagnostic accuracy of MR imaging was 92%. Interobserver agreement and the agreement between imaging and the surgical findings were almost perfect for postganglionic injury ( = 0.81–1, P < .001).
CONCLUSIONS:High-resolution sonography can identify and locate the postganglionic injury associated with the upper and middle trunks. The ability of sonography to evaluate pre- and the postganglionic injury associated with the lower trunk was quite limited. Sonography can be used as a complement to MR imaging; thus, the duration of the MR imaging examination and the need for sedation can be reduced by sonography.
https://ift.tt/2oMXwaU
Adjunctive Efficacy of Intra-Arterial Conebeam CT Angiography Relative to DSA in the Diagnosis and Surgical Planning of Micro-Arteriovenous Malformations [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
Micro-arteriovenous malformations are an underrecognized etiology of intracranial hemorrhage. Our study aimed to assess the adjunctive efficacy of intra-arterial conebeam CTA relative to DSA in the diagnosis and surgical planning of intracranial micro-AVMs.
MATERIALS AND METHODS:We performed a retrospective study of all micro-AVMs (≤1-cm nidus) at our institution. Blinded neuroradiologists qualitatively graded DSA and intra-arterial conebeam CTA images for the detection of specific micro-AVM anatomic parameters (arterial feeder, micronidus, and venous drainer) and defined an overall diagnostic value. Statistical and absolute differences in the overall diagnostic values defined the relative intra-arterial conebeam CTA diagnostic values, respectively. Blinded neurosurgeons reported their treatment approach after DSA and graded the adjunctive value of intra-arterial conebeam CTA to improve or modify treatment. Intra-arterial conebeam CTA efficacy was defined as interobserver agreement in the relative intra-arterial conebeam CTA diagnostic and/or treatment-planning value scores.
RESULTS:Ten patients with micro-AVMs presented with neurologic deficits and/or intracranial hemorrhages. Both neuroradiologists assigned a higher overall intra-arterial conebeam CTA diagnostic value (P < .05), secondary to improved evaluation of both arterial feeders and the micronidus, with good interobserver agreement ( = 0.66, P = .018) in the relative intra-arterial conebeam CTA diagnostic value. Both neurosurgeons reported that integrating the intra-arterial conebeam CTA data into their treatment plan would allow more confident localization for surgical/radiation treatment (8/10; altering the treatment plan in 1 patient), with good interobserver agreement in the relative intra-arterial conebeam CTA treatment planning value ( = 0.73, P = .025).
CONCLUSIONS:Adjunctive intra-arterial conebeam CTA techniques are more effective in the diagnostic identification and anatomic delineation of micro-AVMs, relative to DSA alone, with the potential to improve microsurgical or radiosurgery treatment planning.
https://ift.tt/2PJiinv
Intracranial Serpentine Aneurysms: Spontaneous Changes of Angiographic Filling Pattern [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
Serpentine aneurysms are partially thrombosed aneurysms with an eccentrically located tortuous intra-aneurysmal vascular channel. The large size, distinctive neck anatomy, and supply of the brain parenchyma by the outflow tract pose technical challenges in treatment. The aim of this study was to discuss the endovascular treatment results and illustrate the dynamic nature of serpentine aneurysms. Spontaneous transformation of saccular and fusiform aneurysms into serpentine morphology, along with a case of serpentine-into-fusiform aneurysm transformation during follow-up, is presented.
MATERIALS AND METHODS:A retrospective analysis from 3 institutions revealed 15 patients with serpentine aneurysms who underwent diagnostic evaluation and endovascular treatment. Nine of the 15 patients underwent endovascular occlusion of the parent vessel with detachable balloon or coils. Six of the 15 patients underwent aneurysm and parent artery occlusion with coiling.
RESULTS:In 11 patients, improvement or resolution of symptoms was achieved by an endovascular approach without any treatment-related morbidity. Morbidity related to treatment in the immediate postoperative period was seen in 3 patients, with resolution of the deficits at long-term follow-up in 2 patients and persistence of a mild deficit in 1 patient. Endovascular treatment failed to achieve resolution of symptoms in a case with a basilar tip aneurysm treated by aneurysm coiling.
CONCLUSIONS:Serpentine aneurysms are dynamic structures with spontaneous transformation possible from a saccular or fusiform shape into a serpentine configuration. An endovascular approach by parent vessel occlusion or intra-aneurysmal occlusion is a successful treatment technique for serpentine aneurysms.
https://ift.tt/2NTcLKv
Breath-Hold Blood Oxygen Level-Dependent MRI: A Tool for the Assessment of Cerebrovascular Reserve in Children with Moyamoya Disease [FUNCTIONAL]
BACKGROUND AND PURPOSE:
There is a critical need for a reliable and clinically feasible imaging technique that can enable prognostication and selection for revascularization surgery in children with Moyamoya disease. Blood oxygen level–dependent MR imaging assessment of cerebrovascular reactivity, using voluntary breath-hold hypercapnic challenge, is one such simple technique. However, its repeatability and reliability in children with Moyamoya disease are unknown. The current study sought to address this limitation.
MATERIALS AND METHODS:Children with Moyamoya disease underwent dual breath-hold hypercapnic challenge blood oxygen level–dependent MR imaging of cerebrovascular reactivity in the same MR imaging session. Within-day, within-subject repeatability of cerebrovascular reactivity estimates, derived from the blood oxygen level–dependent signal, was computed. Estimates were associated with demographics and intellectual function. Interrater reliability of a qualitative and clinically applicable scoring scheme was assessed.
RESULTS:Twenty children (11 males; 12.1 ± 3.3 years) with 30 MR imaging sessions (60 MR imaging scans) were included. Repeatability was "good" on the basis of the intraclass correlation coefficient (0.70 ± 0.19). Agreement of qualitative scores was "substantial" ( = 0.711), and intrarater reliability of scores was "almost perfect" ( = 0.83 and 1). Younger participants exhibited lower repeatability (P = .027). Repeatability was not associated with cognitive function (P > .05). However, abnormal cerebrovascular reactivity was associated with slower processing speed (P = .015).
CONCLUSIONS:Breath-hold hypercapnic challenge blood oxygen level–dependent MR imaging is a repeatable technique for the assessment of cerebrovascular reactivity in children with Moyamoya disease and is reliably interpretable for use in clinical practice. Standardization of such protocols will allow further research into its application for the assessment of ischemic risk in childhood cerebrovascular disease.
https://ift.tt/2NPSnd9
Simultaneous Bipedicular Radiofrequency Ablation Combined with Vertebral Augmentation for Local Tumor Control of Spinal Metastases [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
Percutaneous radiofrequency ablation combined with vertebral augmentation has emerged as a minimally invasive treatment for patients with vertebral metastases who do not respond to or have contraindications to radiation therapy. The prevalence of posterior vertebral body metastases presents access and treatment challenges in the unique anatomy of the spine. The purpose of this study was to evaluate the safety and efficacy of simultaneous bipedicular radiofrequency ablation using articulating bipolar electrodes combined with vertebral augmentation for local tumor control of spinal metastases.
MATERIALS AND METHODS:Imaging-guided simultaneous bipedicular radiofrequency ablation combined with vertebral augmentation was performed in 27 patients (33 tumors) with vertebral metastases selected following multidisciplinary consultations, to achieve local tumor control in this retrospective study. Tumor characteristics, procedural details, and complications were documented. Pre- and postprocedural cross-sectional imaging was evaluated to assess local tumor control rates.
RESULTS:Thirty-three tumors were successfully ablated in 27 patients. Posterior vertebral body or pedicle involvement or both were present in 94% (31/33) of cases. Sixty-seven percent (22/33) of the tumors involved ≥75% of the vertebral body volume. Posttreatment imaging was available for 79% (26/33) of the treated tumors. Local tumor control was achieved in 96% (25/26) of tumors median imaging follow up of 16 weeks. No complications were reported, and no patients had clinical evidence of metastatic spinal cord compression at the treated levels.
CONCLUSIONS:Simultaneous bipedicular radiofrequency ablation combined with vertebral augmentation is safe and effective for local tumor control of vertebral metastases. Articulating bipolar electrodes enable the placement and proximity necessary for optimal confluence of the ablation zones. Local tumor control may lead to more durable pain palliation, prevent disease progression, and reduce skeletal-related events of the spine.
https://ift.tt/2PEj4lI
Feasibility, Safety, and Periprocedural Complications Associated with Endovascular Treatment of Ruptured Intracranial Aneurysms according to the Depth of Anesthesia [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
The aim of the present study was to report the feasibility, safety, and periprocedural complications associated with EVT of ruptured intracranial aneurysms according to the depth of anesthesia. In most centers, endovascular treatment of intracranial aneurysm is performed under general anesthesia.
MATERIALS AND METHODS:Between March 2011 and December 2016, a total of 183 consecutive patients with 183 aneurysms were treated endovascularly at the authors' center. The data about the depth of anesthesia (local anesthesia, conscious sedation, deep sedation, and general anesthesia), procedural details, and clinical and radiologic outcomes were reviewed.
RESULTS:A total of 183 consecutive patients with 183 aneurysms (mean age, 60.2 ± 14.8 years; 54 men and 129 women) were successfully treated. Of these, 70 (38.3%) patients underwent endovascular treatment under local anesthesia, 33 (18.0%) patients underwent endovascular treatment under conscious sedation, 78 (42.6%) patients underwent endovascular treatment under deep sedation, and only 2 (1.1%) patients underwent endovascular treatment under general anesthesia. For patients who presented with Hunt and Hess grades 1, 2, 3, 4, and 5, 75%, 59.6%, 59.1%, 53.3%, and 35.3% were treated under local anesthesia or conscious sedation, respectively. The procedure-related complication rates amounted to 8.7% (16/183, with 11 thromboembolic complications and 5 intraprocedural ruptures) overall, and 7.7% (14/183) of complications were symptomatic events. In the patients with good clinical grade (Hunt and Hess 1 or 2), the procedure-related complication rate was 4.1% (4/97), and all complications were symptomatic events under local anesthesia or conscious sedation.
CONCLUSIONS:In the authors' experience, local anesthesia or conscious sedation seemed safe and feasible for the patients with good clinical grade SAH.
https://ift.tt/2NUVG30
Five-Year Longitudinal Study of Neck Vessel Cross-Sectional Area in Multiple Sclerosis [ADULT BRAIN]
BACKGROUND AND PURPOSE:
Alterations of neck vessel cross-sectional area in multiple sclerosis have been reported. Our aim was to investigate the evolution of the neck vessel cross-sectional area in patients with MS and healthy controls during 5 years.
MATERIALS AND METHODS:Sixty-nine patients with MS (44 relapsing-remitting MS, 25 progressive MS) and 22 age- and sex-matched healthy controls were examined twice, 5 years apart, on a 3T MR imaging scanner using 2D neck MR angiography. Cross-sectional areas were computed for the common carotid/internal carotid arteries, vertebral arteries, and internal jugular veins for all slices between the C3 and C7 cervical levels. Longitudinal cross-sectional area differences at each cervical level and the whole-vessel course were tested within study groups and between patients with MS with and without cardiovascular disease using mixed-model analysis and the related-samples Wilcoxon singed rank test. The Benjamini-Hochberg procedure was performed to correct for multiple comparisons.
RESULTS:No significant cross-sectional area differences were seen between patients with MS and healthy controls at baseline or at follow-up. During the follow-up, significant cross-sectional area decrease was found in patients with MS for the common carotid artery–ICAs (C4: P = .048; C7: P = .005; whole vessel: P = .012), for vertebral arteries (C3: P = .028; C4: P = .028; C7: P = .028; whole vessel: P = .012), and for the internal jugular veins (C3: P = .014; C4: P = .008; C5: P = .010; C6: P = .010; C7: P = .008; whole vessel: P = .002). Patients with MS without cardiovascular disease had significantly greater change than patients with MS with cardiovascular disease for internal jugular veins at all levels.
CONCLUSIONS:For 5 years, patients with MS showed significant cross-sectional area decrease of all major neck vessels, regardless of the disease course and cardiovascular status.
https://ift.tt/2PE4dHQ
Review of the Imaging Features of Benign Osteoporotic and Malignant Vertebral Compression Fractures [SPINE]
SUMMARY:
Vertebral compression fractures are very common, especially in the elderly. Benign osteoporotic and malignant vertebral compression fractures have extremely different management and prognostic implications. Although there is an overlap in appearances, characteristic imaging features can aid in the distinction between these 2 types of compression fractures. The aim of this review is to characterize the imaging features of benign and malignant vertebral compression fractures seen with CT, PET, SPECT, and MR imaging.
https://ift.tt/2oMg23h
Comparison of a Photon-Counting-Detector CT with an Energy-Integrating-Detector CT for Temporal Bone Imaging: A Cadaveric Study [HEAD & NECK]
BACKGROUND AND PURPOSE:
Evaluating abnormalities of the temporal bone requires high-spatial-resolution CT imaging. Our aim was to assess the performance of photon-counting-detector ultra-high-resolution acquisitions for temporal bone imaging and compare the results with those of energy-integrating-detector ultra-high-resolution acquisitions.
MATERIALS AND METHODS:Phantom studies were conducted to quantify spatial resolution of the ultra-high-resolution mode on a prototype photon-counting-detector CT scanner and an energy-integrating-detector CT scanner that uses a comb filter. Ten cadaveric temporal bones were scanned on both systems with the radiation dose matched to that of the clinical examinations. Images were reconstructed using a sharp kernel, 0.6-mm (minimum) thickness for energy-integrating-detector CT, and 0.6- and 0.25-mm (minimum) thicknesses for photon-counting-detector CT. Image noise was measured and compared using adjusted 1-way ANOVA. Images were reviewed blindly by 3 neuroradiologists to assess the incudomallear joint, stapes footplate, modiolus, and overall image quality. The ranking results for each specimen and protocol were compared using the Friedman test. The Krippendorff α was used for interreader agreement.
RESULTS:Photon-counting-detector CT showed an increase of in-plane resolution compared with energy-integrating-detector CT. At the same thickness (0.6 mm), images from photon-counting-detector CT had significantly lower (P < .001) image noise compared with energy-integrating-detector CT. Readers preferred the photon-counting-detector CT images to the energy-integrating-detector images for all 3 temporal bone structures. A moderate interreader agreement was observed with the Krippendorff α = 0.50. For overall image quality, photon-counting-detector CT image sets were ranked significantly higher than images from energy-integrating-detector CT (P < .001).
CONCLUSIONS:This study demonstrated substantially better delineation of fine anatomy for the temporal bones scanned with the ultra-high-resolution mode of photon-counting-detector CT compared with the ultra-high-resolution mode of a commercial energy-integrating-detector CT scanner.
https://ift.tt/2NSodWO
Feasibility of a Synthetic MR Imaging Sequence for Spine Imaging [SPINE]
BACKGROUND AND PURPOSE:
Synthetic MR imaging is a method that can produce multiple contrasts from a single sequence, as well as quantitative maps. Our aim was to determine the feasibility of a synthetic MR image for spine imaging.
MATERIALS AND METHODS:Thirty-eight patients with clinical indications of infectious, degenerative, and neoplastic disease underwent an MR imaging of the spine (11 cervical, 8 dorsal, and 19 lumbosacral MR imaging studies). The SyntAc sequence, with an acquisition time of 5 minutes 40 seconds, was added to the usual imaging protocol consisting of conventional sagittal T1 TSE, T2 TSE, and STIR TSE.
RESULTS:Synthetic T1-weighted, T2-weighted, and STIR images were of adequate quality, and the acquisition time was 53% less than with conventional MR imaging. The image quality was rated as "good" for both synthetic and conventional images. Interreader agreement concerning lesion conspicuity was good with a Cohen of 0.737. Artifacts consisting of white pixels/spike noise across contrast views, as well as flow artifacts, were more common in the synthetic sequences, particularly in synthetic STIR. There were no statistically significant differences between readers concerning the scores assigned for image quality or lesion conspicuity.
CONCLUSIONS:Our study shows that synthetic MR imaging is feasible in spine imaging and produces, in general, good image quality and diagnostic confidence. Furthermore, the non-negligible time savings and the ability to obtain quantitative measurements as well as to generate several contrasts with a single acquisition should promise a bright future for synthetic MR imaging in clinical routine.
https://ift.tt/2NRxgXT
Gadolinium Deposition in Deep Brain Structures: Relationship with Dose and Ionization of Linear Gadolinium-Based Contrast Agents [ADULT BRAIN]
BACKGROUND AND PURPOSE:
Dose-dependent association between hyperintensity in deep brain structures on unenhanced T1WIs and gadolinium-based contrast agent administrations has been demonstrated with subsequent histopathological confirmation of gadolinium deposition. Our aim was to determine whether greater exposure to linear gadolinium-based contrast agent administration is associated with higher signal intensity in deep brain structures on unenhanced T1-weighted MR imaging. Secondary objective was to compare signal intensity differences between ionic and nonionic linear gadolinium-based contrast agents.
MATERIALS AND METHODS:Subjects with secondary-progressive MS originally enrolled in a multicenter clinical trial were studied retrospectively. Eighty subjects (high-exposure cohort) received 9 linear gadolinium-based contrast agent administrations (30 nonionic/50 ionic) between week –4 and year 1 and a tenth administration by year 2. One hundred fifteen subjects (low-exposure cohort) received 2 administrations (40 nonionic/75 ionic) between week –4 and year 1 and a third administration by year 2. Signal intensities were measured on unenhanced T1WIs by placing sample-points on the dentate nucleus, globus pallidus, caudate, thalamus, pons, and white matter, and they were normalized using the following ratios: dentate/pons, globus pallidus/white matter, caudate/white matter, and thalamus/white matter.
RESULTS:Between week –4 and year 1, subjects in the high-exposure cohort showed increased signal intensity ratios in all regions (P < .01), while the low-exposure cohort showed only an increase in the dentate nucleus (P = .003). Between years 1 and 2, when both cohorts received only 1 additional gadolinium-based contrast agent, no significant changes were observed. In the high-exposure cohort, significantly higher changes in signal intensity ratios were observed in subjects receiving linear nonionic than in those receiving linear ionic gadolinium-based contrast agents.
CONCLUSIONS:Hyperintensity in deep brain structures from gadolinium deposition is related to the number of doses and the type of linear gadolinium-based contrast agent (nonionic greater than ionic) administration.
https://ift.tt/2oMWWtK
Gadolinium Deposition within the Pediatric Brain: No Increased Intrinsic T1-Weighted Signal Intensity within the Dentate Nucleus following the Administration of a Minimum of 4 Doses of the Macrocyclic Agent Gadoteridol [PEDIATRICS]
BACKGROUND AND PURPOSE:
Our aim was to evaluate whether serial administration of the macrocyclic gadolinium-based contrast agent gadoteridol in children is associated with T1-weighted hyperintensity within the dentate nucleus, an imaging surrogate for gadolinium deposition.
MATERIALS AND METHODS:We identified a retrospective cohort of 10 patients younger than 18 years of age who underwent between 4 and 8 gadoteridol-enhanced MR imaging examinations of the brain from 2016 to 2017. For comparison, we identified a retrospective cohort of 9 pediatric patients who each underwent 6 gadodiamide-enhanced MR imaging examinations. For each examination, both dentate nuclei were contoured on unenhanced images and the mean dentate-to-pons signal intensity ratio was calculated. Dentate-to-pons signal intensity ratios from the first and last scans were compared using paired t tests.
RESULTS:In the gadoteridol group, there was no significant change in the mean dentate-to-pons signal intensity ratio from the first to the last scan (0.99 versus 0.99, P = .59). In the gadodiamide group, there was a significant increase in the mean dentate-to-pons signal intensity ratio from the first to the last scan (0.99 versus 1.10, P = .001).
CONCLUSIONS:Repeat administration of the macrocyclic gadolinium-based contrast agent gadoteridol in children was not associated with T1-weighted dentate hyperintensity, while the repeat administration of the linear gadolinium-based contrast agent gadodiamide was associated with T1-weighted dentate hyperintensity, presumably due to gadolinium deposition.
https://ift.tt/2wO0PDg
Cancers, Vol. 10, Pages 316: The Extracellular Matrix and Pancreatic Cancer: A Complex Relationship
Cancers, Vol. 10, Pages 316: The Extracellular Matrix and Pancreatic Cancer: A Complex Relationship
Cancers doi: 10.3390/cancers10090316
Authors: Maximilian Weniger Kim C. Honselmann Andrew S. Liss
Pancreatic ductal adenocarcinoma (PDAC) has an extraordinarily dense fibrotic stroma that impedes tumor perfusion and delivery of anticancer drugs. Since the extracellular matrix (ECM) comprises the bulk of the stroma, it is primarily responsible for the increased interstitial tissue pressure and stiff mechanical properties of the stroma. Besides its mechanical influence, the ECM provides important biochemical and physical cues that promote survival, proliferation, and metastasis. By serving as a nutritional source, the ECM also enables PDAC cells to survive under the nutrient-poor conditions. While therapeutic strategies using stroma-depleting drugs have yielded disappointing results, an increasing body of research indicates the ECM may offer a variety of potential therapeutic targets. As preclinical studies of ECM-targeted drugs have shown promising effects, a number of clinical trials are currently investigating agents with the potential to advance the future treatment of PDAC. Thus, the present review seeks to give an overview of the complex relationship between the ECM and PDAC.
https://ift.tt/2M31wgN
Decreased methylation in the SNAI2 and ADAM23 genes associated with de-differentiation and haematogenous dissemination in breast cancers
Abstract
Background
In breast cancer (BC), deregulation of DNA methylation leads to aberrant expressions and functions of key regulatory genes. In our study, we investigated the relationship between the methylation profiles of genes associated with cancer invasivity and clinico-pathological parameters. In detail, we studied differences in the methylation levels between BC patients with haematogenous and lymphogenous cancer dissemination.
Methods
We analysed samples of primary tumours (PTs), lymph node metastases (LNMs) and peripheral blood cells (PBCs) from 59 patients with sporadic disseminated BC. Evaluation of the DNA methylation levels of six genes related to invasivity, ADAM23, uPA, CXCL12, TWIST1, SNAI1 and SNAI2, was performed by pyrosequencing.
Results
Among the cancer-specific methylated genes, we found lower methylation levels of the SNAI2 gene in histologic grade 3 tumours (OR = 0.61; 95% CI, 0.39–0.97; P = 0.038) than in fully or moderately differentiated cancers. We also evaluated the methylation profiles in patients with different cancer cell dissemination statuses (positivity for circulating tumour cells (CTCs) and/or LNMs). We detected the significant association between reduced DNA methylation of ADAM23 in PTs and presence of CTCs in the peripheral blood of patients (OR = 0.45; 95% CI, 0.23–0.90; P = 0.023).
Conclusion
The relationships between the decreased methylation levels of the SNAI2 and ADAM23 genes and cancer de-differentiation and haematogenous dissemination, respectively, indicate novel functions of those genes in the invasive processes. After experimental validation of the association between the lower values of SNAI2 and ADAM23 methylation and clinical features of aggressive BCs, these methylation profiles could improve the management of metastatic disease.
https://ift.tt/2oSuSpf
Moving iPSC-Derived Cardiomyocytes Forward to Treat Myocardial Infarction
Human pluripotent stem cell-derived cardiomyocytes represent a promising cell source for cardiac repair. However, their clinical translation is hindered by limited evidence for functional benefits in primate models, potential risks for arrhythmias, and teratoma formation. A recent study by Liu et al. (2018) makes significant progress on these critical issues.
https://ift.tt/2MRpUat
Evolving Visions for Global Stem Cell Institutes
A mere 20 years ago, the promise of stem cell therapies was a distant prospect. Research groups were relatively focused and spread across university departments. Today, the landscape has changed beyond all recognition. The number of stem cell departments, and even institutes, are steadily growing, and there is now an increasing emphasis on translating our current understanding of stem cells into real therapies that benefit patients.
https://ift.tt/2M4EiXB
Future AAVenues for In Utero Gene Therapy
Fetal gene therapy using safe and effective viral vectors no longer remains a distant prospect. Recently in Nature Medicine, Massaro et al. (2018) demonstrated that prenatal intracranial injection of a viral vector results in improved neurologic function, raising the intriguing possibility that in utero gene therapy may be approaching clinical applications.
https://ift.tt/2NoUGHd
Regenerating Eye Tissues to Preserve and Restore Vision
(Cell Stem Cell 22, 834–849; June 1, 2018)
https://ift.tt/2M61pBb
Revert the SIRT: Normalizing SIRT1 Activity in Myelodysplastic Stem Cells
Myelodysplastic syndromes are hematologic malignancies with few treatment options and a propensity to transform to acute myeloid leukemia. In this issue of Cell Stem Cell, Sun et al. (2018) report that low SIRT1 levels in myelodysplastic stem cells contribute to aberrant self-renewal through enabling hyperacetylation and reduced activity of TET2.
https://ift.tt/2Ng8BPZ
Obliterating Obstacles to an Odyssey
Why is reprogramming to generate induced pluripotent stem cells (iPSCs) a protracted and inefficient odyssey? In this issue of Cell Stem Cell, Mor et al. (2018) hypothesize that reprogramming factors paradoxically activate and inhibit pluripotency gene expression and show that eliminating Gatad2a (a NuRD corepressor complex subcomponent) rapidly and efficiently reprograms multiple cell types into iPSCs.
https://ift.tt/2CrLvBA
Mentoring the Next Generation: Andreas Trumpp
Mentor-mentee relationships are essential for professional development, but developing these interpersonal skills is not often highlighted as a priority in scientific endeavors. In a yearlong series, Cell Stem Cell interviews prominent scientists who have prioritized mentorship over the years. Here, we chat with Dr. Andreas Trumpp about his views.
https://ift.tt/2Ng8qUP
Studying Tumor-ReacTive T Cells: A Personalized Organoid Model
Recently in Cell, Dijkstra et al. (2018) introduce a tumor organoid/lymphocyte co-culture-based approach to expand and analyze tumor-specific T cell responses in a patient-specific manner. The platform is applicable for epithelial cancers and may have significant value for clinical translation of novel personalized immunotherapies.
https://ift.tt/2CqRerq
An Unexpected Calm: Mfge8 Controls Stem Cell Quiescence and Maintenance
Radial glia-like neural stem cells (RGLs) in the mouse hippocampus generate neurons throughout life, but RGL maintenance mechanisms remain unclear. In this issue of Cell Stem Cell, Zhou et al. (2018) identified Mfge8, a well-known mediator of the "eat-me" signal, as a factor that reinforces quiescence and protects the RGL niche from depletion.
https://ift.tt/2Ng8jbR
Morphological and immunohistochemical analysis of proteins CASPASE 3 and XIAP in rats subjected to cerebral ischemia and chronic alcoholism
Abstract Purpose: To evaluate histopathological and ultrastructural changes and expression of proteins related to apoptosis CASPASE 3 and XIAP after experimental induction of temporary focal cerebral ischemia (90 minutes) due to obstruction of the middle cerebral artery in alcoholism model. Methods: Forty adult Wistar rats were used, subdivided into 5 experimental groups: control group (C); Sham group (S); Ischemic group (I); Alcoholic group (A); and Ischemic and Alcoholized group (I+A): animals submitted to the same treatment of group A and after four weeks were submitted to focal cerebral ischemia during 90 minutes, followed by reperfusion of 48 hours. Were processed for histopathological analysis and immunohistochemistry (for the protein expression of CASPASE -3 and XIAP). Results: Greater histopathological changes were observed in the animals of groups I and I+A in the three areas analyzed. The neuronal loss was higher in the medial striatum region of the animals of groups I and I + A. The protein expression of CASPASE -3 was higher than that of XIAP in the groups I and I + A for both proteins. Conclusion: The expression of XIAP was slightly higher where the histopathological changes and expression of CASPASE -3 was less evident.
https://ift.tt/2PJeDGm
Correlations of inhaled NO with the cTnI levels and the plasma clotting factor in rabbits with acute massive pulmonary embolism
Abstract Purpose: To investigate the correlation of inhaled nitric oxide (NO) on plasma levels of cardiac troponin I (cTnI) and von Willebrand factor (vWF), glycoprotein (GP) IIb/IIIa, granule membrane protein 140 (GMP-140) in rabbits with acute massive pulmonary embolism (PE). Methods: Thirty apanese white rabbits were divided into 3 groups, thrombus were injected in model group (n = 10), NO were inhalated for 24 h after massive PE in NO group (n = 10), saline were injected in control group (n = 10). The concentrations of vWF, GP IIb/IIIa, GMP-140 and cTnI were tested at 4, 8, 12, 16, 20, and 24 h, Correlation analyses were conducted between cTnI and vWF, GP IIb/IIIa, and GMP-140 by Pearson's correlation. Results: The concentration of cTnI and vWF, GP IIb/IIIa, and GMP-140 was increased in the model group, compared to control group. In the inhaled group, the concentrations of cTnI, vWF, GP IIb/IIIa, and GMP-140 were reduced compared to model group. There was a positive correlation between cTnI and vWF, GP IIb/IIIa, and GMP-140. Conclusion: Inhaled nitric oxide can lead to a decrease in levels of cardiac troponin I, von Willebrand factor, glycoprotein, and granule membrane protein 140, after an established myocardial damage, provoked by acute massive pulmonary embolism.
https://ift.tt/2oJcn6m
Bacterial cellulose to reinforce urethrovesical anastomosis. A translational study
Abstract Purpose: To evaluate the efficacy of the cellulosic exopolysaccharide membrane (CEM) as a urethral reinforcement for urethrovesical anastomosis. Methods: Twenty eight rabbits were submitted to urethrovesical anastomosis with or without CEM reinforcement. The animals were divided into 4 groups: C7, CEM7, C14 and CEM14: (C= only anastomosis or CEM = anastomosis + CEM), evaluated after 7 weeks, and 14 weeks. The biointegration and biocompatibility of CEM were evaluated according to stenosis, fistula, urethral wall thickness, urethral epithelium, rate of inflammation and vascularization. Results: Between the two experimental groups, the difference in the number of stenosis or urinary fistula was not statistically significant. The morphometric analysis revealed preservation of urethral lumen, well adhered CEM without extrusion, a controlled inflammatory process and implant vascularization. The urothelium height remained constant over time after CEM reinforcement and the membrane wall was thicker, statistically, after 14 weeks. Conclusion: The absence of extrusion, stenosis or urinary fistula after 14 weeks of urethrovesical anastomosis demonstrates cellulosic exopolysaccharide membrane biocompatibility and biointegration with tendency to a thicker wall.
https://ift.tt/2NTypyk
Prospective clinical assessment of tibial tuberosity advancement for the treatment of cranial cruciate ligament rupture in dogs
Abstract Purpose: To evaluate clinically dogs that underwent tibial tuberosity advancement (TTA) six months previously. Methods: Dogs of various breeds, gender, weight, and age that had CCL rupture and underwent TTA for treatment were included in this study. Parapatellar arthrotomy was performed in all patients to assess the joint for a ruptured ligament and meniscal injury before the TTA. The appropriate cage for the TTA was chosen with planning surgery. The surgical procedure was performed according to the literature, using a modified Maquet technique. Six months after surgery, lameness during walking; muscular atrophy; crepitation, cranial drawer and tibial compression tests and quality of life based on owner's evaluation were assessed. Results: Postoperative complications were observed in only one knee (4.76%), with a surgical site seroma. The mean lameness score at walking was 0.29 (± 0.64). The mean score regarding muscular atrophy was 0.95 (± 1.56). The mean score of the cranial drawer test, in a range from 0 to 5, was 1.52 (± 1.54). The owners rated the dog's quality of life as excellent in 44%, good in 30%, and moderate in 17%. Conclusion: This clinical study supports the affirmation that patients who undergo TTA for treatment of CCL rupture have an acceptable response.
https://ift.tt/2oO2JiJ
Comparative safety assessments of the biosimilar APZ001 and Erbitux in pre-clinical animal models
Abstract Purpose: To evaluate the toxicity of Erbitux as well as its biosimilar APZ001 antibody (APZ001) in pre-clinical animal models including mice, rabbits and cynomolgus monkeys. Methods: We performed analysis of normal behavior activity, autonomic and non-autonomic nervous functions, nervous-muscle functions, nervous excitability and sensorimotor functions on CD-1 mice. Subsequently, we studied that effects of APZ001 and Erbitux on respiratory system, cardiovascular system and kidney in Cynomolgus monkey models and performed local tolerance experiments on New Zealand rabbits. Results: The comparisons between APZ001 and Erbitux showed no significant differences in mice autonomic nervous system, nervous muscle functions, non-autonomic nervous functions, nervous excitability and sensorimotor functions between treated and untreated group (p>0.05). APZ001 and Erbitux showed negative effect on CD-1 mice in the present of pentobarbital sodium anesthesia (p>0.05). Single administrations of high, medium or low doses of APZ001 did not lead to monkey urine volume alterations (p>0.05). In human tissues, APZ001 and Erbitux showed positive signals in endocardium, lung type II alveolar epithelial cell and surrounding vessels, but showed negative results in kidney and liver tissues. No hemolysis phenomenon and serious side-effects in vessels and muscles were observed in rabbits when administrated with APZ001 and Erbitux respectively. Conclusion: The safety comparisons between APZ001 antibody and Erbitux showed that these two antibodies showed highly similarities in mice, rabbits and cynomolgus monkey animal models in consideration of pharmaceutical effects, indicating APZ001 might be a suitable substitute for Erbitux.
https://ift.tt/2NVFazP
The role of vitamin C in the gene expression of oxidative stress markers in fibroblasts from burn patients
Abstract Purpose: To assess the action of vitamin C on the expression of 84 oxidative stress related-genes in cultured skin fibroblasts from burn patients. Methods: Skin samples were obtained from ten burn patients. Human primary fibroblasts were isolated and cultured to be distributed into 2 groups: TF (n = 10, fibroblasts treated with vitamin C) and UF (n = 10, untreated fibroblasts). Gene expression analysis using quantitative polymerase chain reaction array was performed for comparisons between groups. Results: The comparison revealed 10 upregulated genes as follows: arachidonate 12-lipoxygenase (ALOX12), 24-dehydrocholesterol reductase (DHCR24), dual oxidase 1 (DUOX1), glutathione peroxidase 2 (GPX2), glutathione peroxidase 5 (GPX5), microsomal glutathione S-transferase 3 (MGST3), peroxiredoxin 4 (PRDX4), phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 (P-REX1), prostaglandin-endoperoxide synthase 1 (PTGS1), and ring finger protein 7 (RNF7). Conclusion: Cultured fibroblasts obtained from burn patients and treated with vitamin C resulted in 10 differentially expressed genes, all overexpressed, with DUOX1, GPX5, GPX2 and PTGS1 being of most interest.
https://ift.tt/2wPCywJ
Simulated training of a laparoscopic vesicourethral anastomosis
Abstract Purpose: To develop a model and curriculum for simulated training of an effective and well accepted laparoscopic vesicourethral anastomosis (VUA). Methods: Experimental longitudinal study of quantitative character. The sample consisted of 12 general surgery residents and 6 urology residents (R3). The training consisted of making twelve VUAs on synthetic organs. The training was divided into four sessions and accompanied by an instructor who performed positive feedback. The evaluation of the anastomoses considered the time and the analysis of the operative technique through the global evaluation scale Objective Structured Assessment of Technical Skills (OSATS). Results: Residents showed a reduction in operative time and evolution in the surgical technique statistically significant (p<0.01). The best-rated items were the facilitator positive feedback and the fact that the training was carried out at the teaching hospital premises. Conclusions: The proposed training model was well accepted and proved to be effective in reducing operative time and improving laparoscopic skills. The training should be fractionated (4 sessions in 3 weeks), repetitive (12 anastomoses) and have positive feedback.
https://ift.tt/2PKEca0
Liver ischemia and reperfusion injury. Pathophysiology and new horizons in preconditioning and therapy
Abstract It is well known that during hepatic operative procedures, it is often critical that the irrigation is interrupted to avoid possible bleeding, blood transfusions, variable intensities, and their short and long-term consequences. It was believed in the past that the flow interruption should not exceed 20 minutes, which limited the use of this maneuver. However, it has been postulated that ischemia could be maintained for more than 60 minutes in healthy livers. The present paper review includes: 1) A brief introduction to justify the rationale of the review design; 2) Aspects of the pathophysiology of the three stages of the liver ischemia-reperfusion injury; 3) The innate and acquired immunity; 4) Oxidative stress; 5) Apoptosis and autophagy, Some essential biomarkers (Tumor Necrosis Factor-α, nitric oxide, metalloproteinases); and, finally; 6) Preventive ("cheating") strategies, non-pharmacological and pharmacological options to treat the liver IR injury.
https://ift.tt/2oKPwaz
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
