Background. Postpartum depression (PPD) and preeclampsia (PE) are both common diseases in obstetrics that affect maternal health and infant development. However, the relationship between the two diseases still requires clarification. Objective. The purpose of this study was to (1) determine the incidence rate of PPD in patients with PE and (2) identify the association between the prevalence of PPD and the severity of PE. Methods. We conducted a retrospective analysis of women with and without PE who delivered between January 1, 2017, and August 30, 2018, in the First Affiliated Hospital of Chongqing Medical University. We used a questionnaire survey methodology that included the Edinburgh Postnatal Depression Scale (EPDS) to test the influence of PE on the development of new-onset PPD in the 6 weeks after delivery. We determined PPD based on a score ≥10 on the EPDS. Bivariate analysis was used to compare data between the two groups. Results. A total of 180 women participated in this study. Thirty-five people screened positive for PPD, while the remaining 145 screened negative. The prevalence of PPD was 26.67% (24/90) in patients with PE, which was two times the prevalence in normal women (12.22%). Multiple logistic regression showed that women who had PE had nearly 3-fold increased odds of PPD compared to normal women and the risk of PPD increased with the aggravation of PE. Patients with severe PE had a more than 4-fold increased risk of screening positive for PPD. Conclusion. PE was independently associated with PPD. Furthermore, the risk of PPD seemed to increase with the aggravation of PE. Thus, additional prevention efforts and support methods should be provided for women with PE to reduce the incidence of PPD.
https://ift.tt/2U576nI
Τρίτη 26 Φεβρουαρίου 2019
Development of Postpartum Depression in Pregnant Women with Preeclampsia: A Retrospective Study
Discrimination between breast invasive ductal carcinomas and benign lesions by optimizing quantitative parameters derived from dynamic contrast-enhanced MRI using a semi-automatic method
Abstract
Background
To propose a semi-automatic method for distinguishing invasive ductal carcinomas from benign lesions on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
Methods
142 cases were included. In the conventional method, the region of interest for a breast lesion was drawn manually and the corresponding mean time–signal intensity curve (TIC) was qualitatively categorized. Only one quantitative parameter was obtained: the maximum slope of increase (MSI). By contrast, the proposed method extracted the suspicious breast lesion semi-automatically. Besides MSI, more quantitative parameters reflecting perfusion information were derived from the mean TIC and lesion region, including the signal intensity slope (SIslope), initial percentage of enhancement, percentage of peak enhancement, early signal enhancement ratio, and second enhancement percentage. The mean TIC was categorized quantitatively according to the value of SIslope. Regression models were established. The diagnostic performance differed between the new and conventional methods according to the Wilcoxon rank-sum test and receiver operating characteristic analysis.
Results
According to the TIC categorization results, the accuracies of the traditional and the new method were 59.16% and 76.05%, respectively (P < 0.05). The accuracy was 63.35% for MSI, which was derived from the manual method. For the semi-automatic method, the accuracies were 81.0% and 78.9% for the lesion region and the corresponding mean TIC regression models, respectively.
Conclusions
The results demonstrate that our proposed semi-automatic method is beneficial for discriminating breast IDCs and benign lesions based on DCE-MRI, and this method should be considered as a supplementary tool for subjective diagnosis by clinical radiologists.
https://ift.tt/2Vno8hi
Optimal use of anthracycline-free perioperative chemotherapy in HER2-positive breast cancer patients
Abstract
Purpose
In adjuvant settings of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, anthracycline-based chemotherapy followed by taxane and trastuzumab is a standard regimen. Recent studies have reported the use of anthracycline-free adjuvant chemotherapy in selected HER2-positive breast cancer patients. We conducted a single-center retrospective study to identify the characteristics of HER2-positive breast cancer patients for whom anthracyclines can be safely omitted.
Methods
A total of 238 women were diagnosed with HER2-positive breast cancer and treated with neoadjuvant and/or adjuvant chemotherapy between January 1, 2008 and December 31, 2015 at Keio University Hospital. They were divided in two cohorts: an "anthracycline" cohort of 112 anthracycline-treated women and a "no anthracycline" cohort of 126 anthracycline-untreated women. Survival outcomes were estimated by Kaplan–Meier method.
Results
The 3-year disease-free survival rates in the no-anthracycline and anthracycline cohorts were 91.3% and 93.1%, respectively (P = 0.692). After using a statistical method with inverse probability of treatment weighting to minimize the selection bias, no significant differences were observed between the two cohorts (adjusted hazard ratio for disease-free survival: 1.042; P = 0.909). Stratified by tumor size, no significant differences were observed between the two cohorts in the cT1N0 and cT2N0 subsets (P = 0.516 and P = 0.579, respectively). The recurrence rate was low among patients who achieved pathological complete response after receiving neoadjuvant chemotherapy with or without anthracyclines.
Conclusion
Our study suggests that anthracyclines can be safely omitted in selected patients with HER2-positive breast cancer, who have cT1N0 or cT2N0 and achieved pathological complete response after receiving neoadjuvant chemotherapy.
https://ift.tt/2EzbMNu
Welcome to Volume 8 of the International Journal of Hematologic Oncology
International Journal of Hematologic Oncology, Ahead of Print.
https://ift.tt/2tG9963
Comprehensive review of acute oesophageal necrosis
Acute oesophageal necrosis, also known as 'black oesophagus', is a rare condition characterised by the black discolouration of the oesophageal mucosa on endoscopy and involves the distal oesophagus in majority of cases but may also extend proximally. A number of conditions are found to be associated with it and it is thought to occur due to a combination of hypovolaemia and inadequate oesophageal protective mucosal barrier function. Gastric secretions may have a direct effect on the oesophageal mucosa. We present a case of a woman who presented with haematemesis and significant hypotension after a session of haemodialysis. Black oesophagus was confirmed on esophagogastroduodenoscopy. She was given two units of packed red blood cells and one unit of platelets, and started on a pantoprazole infusion. However, despite rigorous attempts at resuscitation the patient failed to recover.
https://ift.tt/2TmtmMI
Temporal bone involvement of IgG4-related disease: a rare condition misleading to petrous apicitis causing lateral rectus palsy
IgG4-related disease (IgG4-RD) of temporal bone is rare and clinical manifestation mimics infection. A 19-year-old female presented with progressive left earache and intermittent left nasal obstruction. Then, she rapidly developed left lateral rectus palsy. The physical examination revealed mild redness of left tympanic membrane and a small nasal polyp from the left middle meatus. CT scan showed left petrous apicitis and enhancing sinonasal mucosa. Therefore, Gradenigo's syndrome was first considered. The empirical intravenous antibiotic was immediately prescribed and surgery was performed. The intraoperative pale soft tissue mass in middle ear and polyp in the left nasal cavity were sent for pathological examination and found positive immunohistochemical stains for IgG4 in plasma cells. Systemic corticosteroid, the first-line treatment, was started and her symptoms were finally recovery.
https://ift.tt/2Nv7rh8
Endoscopic control of gastric emptying after administration of intravenous erythromycin in an awake patient scheduled for urgent rigid bronchoscopy
Certain interventional pulmonology procedures such as the placement of a tracheal stent or resection of stenosing tracheal tumours require rigid bronchoscopy under general anaesthesia. Unlike an endotracheal tube with a cuff, the rigid bronchoscope only partially protects the airway from bronchoaspiration. For this reason, this procedure is performed on an elective basis in fasted patients. We describe the case of a 60-year-old man with acute respiratory distress requiring emergent rigid bronchoscopy following distal migration of a tracheal stent. One hour before the procedure, the patient had eaten a full meal. Gastric emptying was accelerated by perfusion of intravenous erythromycin and verified by endoscopy with a small diameter gastric endoscope under local anaesthesia. This 1 min procedure was very well tolerated by the patient and allowed to verify with certainty that the stomach was empty. The urgent rigid bronchoscopy for stent retrieval could then be performed safely without any risk of bronchoaspiration.
https://ift.tt/2TlMb2D
Case of autoimmune polyglandular syndrome type 2: how we uncovered the diagnosis
A 24-year-old man with no significant medical history presented to the medical clinic with vomiting and giddiness for 2 days, loss of appetite for 1 month and progressive fatigability for the preceding 4 months. On examination, he was found to be hypotensive and was admitted to the hospital for work-up. Considering his abnormal labs and physical findings, he was worked up and was diagnosed with primary adrenal insufficiency. On further work-up for the aetiology of his Addison's disease, he was found to have concurrent autoimmune thyroiditis and vitiligo. A final diagnosis of autoimmune polyglandular syndrome type 2 was made. The patient was started on hormone replacement therapy and reported improvement of symptoms on 3-month follow-up visit.
https://ift.tt/2Nv7nxU
Uncommon presentation of medication-related osteonecrosis of the mandible in a patient with metastatic prostate cancer
An 82-year-old man with a background of prostate carcinoma and bony metastases presented with bilateral discharging neck fistulae. Two years prior to presentation, the patient had been treated with intravenous zoledronic acid for 1 year as part of chemotherapy. Intraoral examination revealed extensive bilateral medication-related osteonecrosis, with orocutaneous fistulae within the neck. Treatment comprised removal of loose necrotic bone sequestrae, debridement of the fistulae and long-term administration of antibiotics, vitamin E and pentoxifylline. Four weeks later, the orocutaneous fistulae had healed.
https://ift.tt/2NuBtRV
Pharyngocutaneous fistula caused by dried 'Kombu (edible seaweed) after total laryngectomy
The most common early complication after total laryngectomy is pharyngocutaneous fistula (PCF). However, there are no reports of PCF after total laryngectomy caused by 'Kombu' (edible seaweed) as a foreign body in the digestive tract. A 68-year-old Japanese man had undergone total laryngectomy 5 years previously. He presented with PCF, neck swelling and pain. Video endoscopy showed that a dark green foreign body obstructed the digestive tract. PCF was successfully treated via emergency surgery comprising abscess drainage, foreign body removal and fistula closure. The foreign body was kombu. Clinicians who perform total laryngectomy should know the potential dangers of consuming hygroscopic food items that can cause bolus obstruction of the upper digestive tract and pharyngeal abscess and perforation.
https://ift.tt/2TjVIqW
Unusual complication of an Alaskan cruise: thinking outside the box
A 69-year-old man with a medical history of hypertension and diabetes presented with altered mental status once he returned from a 14-day Alaskan cruise. An extensive workup for stroke was negative. His physical examination was normal without any focal motor deficits, but he had developed memory loss and paresthesia. He admitted to eating a lot of fish when he was in Alaska. The whole-blood mercury level was found to be elevated. He was managed conservatively and his symptoms resolved completely in a few days. This led to a diagnosis of organic mercury toxicity.
https://ift.tt/2Nwf1rN
Arterioportal fistula after partial gastrectomy treated with coil embolisation
Arterioportal fistulas are a rare complication of abdominal interventions. They can remain asymptomatic for a long time and manifest with symptoms of portal hypertension. We present the case of a 65-year-old man admitted to the emergency room with increasing fatigue and melena. He had a history of partial gastrectomy with Billroth II reconstruction 40 years earlier for peptic ulcer perforation. On physical examination, he was pale and presented a machinery-type murmur in the epigastric area. Blood tests revealed iron deficiency anaemia of 5.6 g/dL. During hospitalisation, he required several blood transfusions and maintained melenas. An abdominal CT angiography showed a fusiform aneurysm of the left gastric artery draining to the venous portal-splenic confluent. He was successfully treated with transarterial coil embolisation of the left gastric artery aneurysm. The correct diagnosis of arterioportal fistulas can be very challenging, whereas the standard treatment with coil embolisation offers a low morbidity resolution of symptoms.
https://ift.tt/2TlM1Z5
Rare mimic of recurrent anaphylaxis
The distinction between true anaphylaxis and conditions that mimic it can be challenging. We present the unique case of a 23-year-old woman treated for recurrent episodes of anaphylaxis over the course of 11 years and the subsequent discovery of an unlikely condition. We also discuss our approach in managing cases where an anaphylactic mimic is suspected.
https://ift.tt/2NupS5s
Endophthalmitis with bilateral deafness from disseminated Streptococcus suis infection
Streptococcus suis is a Gram-positive cocci bacterium that are found mainly in pigs and can be transmitted to human through pigs or pork exposure. The disease is mainly found among occupations involving swine contact in western countries whereas in Asia the disease is usually contracted through raw pork consumption. In this case report, we present a case of a middle-aged Thai man who acquired the infection from raw pork consumption. He presented with endogenous endophthalmitis with infective spondylodiscitis, sepsis and meningitis and later developed blindness of the right eye and permanent bilateral hearing loss disseminated from S. suis infection. Our report suggests that S. suis infection be considered as a causative factor in patient presenting with established clinical symptoms and predisposing factors. Cultural habit of eating raw pork should be taken into account especially in Asian countries.
https://ift.tt/2NsXCA4
Tumor suppressor MCPH1 regulates gene expression profiles related to malignant conversion and chromosomal assembly
Strong inherited predisposition to breast cancer is estimated to cause about 5–10% of all breast cancer cases. As the known susceptibility genes, such as BRCA1 and BRCA2, explain only a fraction of this, additional predisposing genes and related biological mechanisms are actively being searched for. We have recently identified a recurrent MCPH1 germline mutation, p.Arg304ValfsTer3, as a breast cancer susceptibility allele. MCPH1 encodes a multifunctional protein involved in maintenance of genomic integrity and it is also somatically altered in various cancer types, including breast cancer. Additionally, biallelic MCPH1 mutations are causative for microcephaly and at cellular level premature chromosome condensation. To study the molecular mechanisms leading to cancer predisposition and malignant conversion, here we have modeled the effect of MCPH1 p.Arg304ValfsTer3 mutation using gene‐edited MCF10A breast epithelial cells. As a complementary approach, we also sought for additional potential cancer driver mutations in MCPH1 p.Arg304ValfsTer3 carrier breast tumors. We show that mutated MCPH1 de‐regulates transcriptional programs related to invasion and metastasis and leads to downregulation of histone genes. These global transcriptional changes are mirrored by significantly increased migration and invasion potential of the cells as well as abnormal chromosomal condensation both before and after mitosis. These findings provide novel molecular insights to MCPH1 tumor suppressor functions and establish a role in regulation of transcriptional programs related to malignant conversion and chromosomal assembly. The MCPH1 p.Arg304ValfsTer3 carrier breast tumors showed recurrent tumor suppressor gene TP53 mutations, which were also significantly over‐represented in breast tumors with somatically inactivated MCPH1.
This article is protected by copyright. All rights reserved.
https://ift.tt/2H0Hk0l
What is the rate-limiting step towards aging? Chemical reaction kinetics might reconcile contradictory observations in experimental aging research
Abstract
Modern geroscience is divided as regards the validity of the free radical theory of aging. Thermodynamic arguments and observations from comparative zoology support it, whereas results from experimental manipulations in representative animal species sometimes strongly contradict it. From a comparison of the multi-step aging process with a linear metabolic pathway (glycolysis), we here argue that the identification of the rate-limiting kinetic steps of the aging cascade is essential to understand the overall flux through the cascade, i.e., the rate of aging. Examining free radical reactions as a case in point, these reactions usually occur as chain reactions with three kinetically independent steps: initiation, propagation, and termination, each of which can be rate-limiting. Revisiting the major arguments in favor and against a role of free radicals in aging, we find that the majority of arguments in favor point to radical propagation as relevant and rate-limiting, whereas almost all arguments in disfavor are based on experimental manipulations of radical initiation or radical termination which turned out to be ineffective. We conclude that the overall lack of efficacy of antioxidant supplementation (which fosters termination) and antioxidant enzyme overexpression (which inhibits initiation) in longevity studies is attributable to the fact that initiation and termination are not the rate-limiting steps of the aging cascade. The biological and evolutionary plausibility of this interpretation is discussed. In summary, radical propagation is predicted to be rate-limiting for aging and should be explored in more detail.
https://ift.tt/2GR0WEO
Isolation by Distance, Source-Sink Population Dynamics and Dispersal Facilitation by Trade Routes: Impact on Population Genetic Structure of a Stored Grain Pest
Population genetic structure of agricultural pests can be impacted not only by geographic distance and the broader ecological and physical barriers but also by patterns related to where crops are produced and how they are moved after harvest. Stored-product pests, for instance, specialize in exploiting grains such as wheat and rice from on-farm storage through transportation to final processing at often geographically distant locations; therefore human-aided movement may impact their dispersal. Although stored product insects are associated with stored grain, they can also exploit resources in the surrounding environments so different ecological regions where the grain is grown and stored may also influence population structure. Here we used 1,156 SNP markers to investigate how geographic distance, ecological and agricultural variables can impact the genetic structure and gene flow of the stored food pest beetle Rhyzopertha dominica. We found a substantial degree of admixture between weakly structured populations in the US. Ecological regions were more important in explaining R. dominica population structure than crop type, suggesting insect movement between wheat and rice grain distribution channels. We have also found a significant correlation between the genetic and geographical distance (i.e., isolation by distance). However, our modeling approach combining the ecological and management variables has highlighted the importance of the volume of grain received by a location in the dispersal dynamics of the pest. The first-generation migrant analysis offered additional supported to movement over great distances that are likely associated with grain movement. Our data suggest that a multitude of factors play small but significant parts in the movement dynamics of the pest. The beetles can take advantage of the source-sink dynamic of grain movement in the US, but also engage in a high rate of movement at the local scale. Understanding population structure for R. dominica will provide insights into the potential for local processes of adaptation and broader patterns of movement that will impact management programs and the potential for spread of resistance genes.
https://ift.tt/2Ua9rOl
Gaussian-Distributed Codon Frequencies of Genomes
DNA encodes protein primary structure using 64 different codons to specify 20 different amino acids and a stop signal. Frequencies of codon occurrence when ordered in descending sequence provide a global characterization of a genome's preference (bias) for using the different codons of the redundant genetic code. Whereas frequency/rank relations have been described by empirical expressions, here we propose a statistical model in which two different forms of codon usage co-exist in a genome. We investigate whether such a model can account for the range of codon usages observed in a large set of genomes from different taxa. The differences in frequency/rank relations across these genomes can be expressed in a single parameter, the proportion of the two codon compartments. One compartment uses different codons with weak bias according to a Gaussian distribution of frequency, the other uses different codons with strong bias. In prokaryotic genomes both compartments appear to be present in a wide range of proportions, whereas in eukaryotic genomes the compartment with Gaussian distribution tends to dominate. Codon frequencies that are Gaussian-distributed suggest that many evolutionary conditions are involved in shaping weakly-biased codon usage, whereas strong bias in codon usage suggests dominance of few evolutionary conditions.
https://ift.tt/2BWQ83M
The Genetics and Genome-Wide Screening of Regrowth Loci, a Key Component of Perennialism in Zea diploperennis
Perennialism is common among the higher plants, yet little is known about its inheritance. Previous genetic studies of the perennialism in Zea have yielded contradictory results. In this study, we take a reductionist approach by specifically focusing on one trait: regrowth (the plant's ability to restart a new life cycle after senescence on the same body). To address this, six hybrids were made by reciprocally crossing perennial Zea diploperennis Iltis, Doebley & R. Guzman with inbred lines B73 and Mo17 and Rhee Flint, a heirloom variety, of Z. mays L. ssp. mays. All the F1 plants demonstrated several cycles of growth, flowering, senescence and regrowth into normal flowering plants, indicating a dominant effect of the Z. diploperennis alleles. The regrowability (i.e. the plants' ability to regrow after senescence) was stably transmitted to progeny of the hybrids. Segregation ratios of regrowth in the F2 generations are consistent with the trait controlled by two dominant, complementary loci, but do not exclude the influence of other modifiers or environment. Genome-wide screening with genotyping-by-sequencing technology indicated two major regrowth loci, regrowth 1 (reg1) and regrowth 2 (reg2), were on chromosomes 2 and 7, respectively. These findings lay the foundation for further exploration of the molecular mechanism of regrowth in Z. diploperennis. Importantly, our data indicate that there is no major barrier to transferring this trait into maize or other grass crops for perennial crop development with proper technology, which enhances sustainability of grain crop production in an environmentally friendly way.
https://ift.tt/2BURaNU
Diagnosis and Management of Autoimmune Dementia
Abstract
Purpose of review
To describe the clinical, laboratory, and MRI features that characterize cognitive decline in the setting of central nervous system (CNS) autoimmunity, and provide an overview of current treatment modalities.
Recent findings
The field of autoimmune neurology is rapidly expanding due to the increasing number of newly discovered autoantibodies directed against specific CNS targets. The clinical syndromes associated with these autoantibodies are heterogeneous but frequently share common, recognizable clinical, and MRI characteristics. While the detection of certain autoantibodies strongly suggest the presence of an underlying malignancy (onconeural autoantibodies), a large proportion of cases remain idiopathic. Cognitive decline and encephalopathy are common manifestations of CNS autoimmunity, and can mimic neurodegenerative disorders. Recent findings suggest that the frequency of autoimmune encephalitis in the population is higher than previously thought, and potentially rivals that of infectious encephalitis. Moreover, emerging clinical scenarios that may predispose to CNS autoimmunity are increasingly been recognized. These include autoimmune dementia/encephalitis post-herpes simplex virus encephalitis, post-transplant and in association with immune checkpoint inhibitor treatment of cancer. Early recognition of autoimmune cognitive impairment is important given the potential for reversibility and disability prevention with appropriate treatment.
Summary
Autoimmune cognitive impairment is treatable and may arise in a number of different clinical settings, with important treatment implications. Several clinical and para-clinical clues may help to differentiate these disorders from dementia of other etiologies.
https://ift.tt/2EiE4dy
New Therapeutic Options for Fragile X Syndrome
Abstract
Purpose of review
The purpose of this review is to provide an overview of current research and clinical practice guidelines in fragile X syndrome (FXS) with regard to therapeutic approaches in the management of this condition. The authors summarize and discuss findings from relevant preclinical studies and results from clinical trials in human subjects with FXS. Additionally, we provide an outline of the basic framework for understanding and providing educational and psychosocial supports for these individuals.
Recent findings
Current treatments in FXS are largely symptom based and focused on managing associated psychiatric and behavioral co-morbidities. While data from animal studies has been promising in providing targeted treatments to correct the underlying deficits at the cellular level, there have not been as robust findings in human trials. There are several targeted treatments for FXS currently under development.
Summary
Individuals with FXS present with several behavioral challenges including anxiety, social withdrawal, ADHD, hyperarousal, self-injury, and aggression. Therapeutic services are often necessary, such as behavioral intervention, speech and language therapy, occupational therapy, and individualized educational support; adjunctive psychopharmacologic treatment is often helpful as well. It is important to address these symptoms and weigh the evidence for the use of medications that target the underlying neurobiology and pathophysiology of the syndrome.
https://ift.tt/2T4VYuA
Eligibility criteria for phase I clinical trials: tight vs loose?
Abstract
Purpose
The purpose of the current study is to analyze a series of phase I cancer clinical trials, examine and compare trial protocols based on patients' eligibility criteria.
Methods
We evaluated all dose escalation phase I trial protocols with accessible or published results performed at Institute for Drug Development, Cancer Therapy and Research Center (San Antonio) between 1991 and 2016. Study protocols were categorized as non-restrictive (NRP) or restrictive (RP) based on several eligibility parameters. Fisher's Exact and Chi-square tests were used to compare characteristics of NRP and RP.
Results
Of 284 protocols screened, 231 dose escalation phase I trial protocols (with accessible results) of solid tumors were included in this review. There were 145 NRP (involving 3190 patients) and 86 RP (involving 1892 patients). The median number of exclusion criteria for NRP and RP were 14 and 23, respectively. The most common reasons that made trial protocol to be restrictive were ECOG ≤ 1, strict requirements for renal or hepatic function (≤ 2.5 times upper limit of normal) and exclusion of subjects with brain metastases. The median accrual time for NRP was significantly shorter as compared to RP (17 vs 26 months). The median number of dose levels explored in NRP and RP were 9 and 6, respectively. RP had a higher screen failure as well as premature closure rate. The rates of DLTs, SAEs, toxicity-related death and response were not different between the two groups.
Conclusions
Our study findings are in support of devising well thought and justified phase I study eligibility criteria.
https://ift.tt/2VswzId
Additional Pediatric Cancer Funding in the Offing? [News in Brief]
Researchers hope President Trump's call for $500 million over 10 years will support basic research, drug development.
https://ift.tt/2IA3skq
High hepatic expression of PDK4 improves survival upon multimodal treatment of colorectal liver metastases
High hepatic expression of PDK4 improves survival upon multimodal treatment of colorectal liver metastases
High hepatic expression of PDK4 improves survival upon multimodal treatment of colorectal liver metastases, Published online: 27 February 2019; doi:10.1038/s41416-019-0406-9
High hepatic expression of PDK4 improves survival upon multimodal treatment of colorectal liver metastaseshttps://ift.tt/2EBikeB
Tissue-infiltrating immune cells as prognostic markers in oral squamous cell carcinoma: a systematic review and meta-analysis
Tissue-infiltrating immune cells as prognostic markers in oral squamous cell carcinoma: a systematic review and meta-analysis
Tissue-infiltrating immune cells as prognostic markers in oral squamous cell carcinoma: a systematic review and meta-analysis, Published online: 27 February 2019; doi:10.1038/s41416-019-0409-6
Tissue-infiltrating immune cells as prognostic markers in oral squamous cell carcinoma: a systematic review and meta-analysishttps://ift.tt/2VqBc5x
Body mass index and Hodgkin's lymphoma: UK population-based cohort study of 5.8 million individuals
Body mass index and Hodgkin's lymphoma: UK population-based cohort study of 5.8 million individuals
Body mass index and Hodgkin's lymphoma: UK population-based cohort study of 5.8 million individuals, Published online: 27 February 2019; doi:10.1038/s41416-019-0401-1
Body mass index and Hodgkin's lymphoma: UK population-based cohort study of 5.8 million individualshttps://ift.tt/2EBii6t
Correction: Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts
Correction: Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts
Correction: Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts, Published online: 27 February 2019; doi:10.1038/s41416-019-0408-7
Correction: Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohortshttps://ift.tt/2VnofsW
Sufficient Investment Could Reduce HIV Epidemic by 2030
TUESDAY, Feb. 26, 2019 -- New HIV infections could be reduced and prevalence could begin to decline by 2030 with sufficient investment, including meeting 95 percent targets for diagnosis, care retention, and viral suppression by 2025, according to a...
https://ift.tt/2ThnNiv
Overlapping Surgery Appears Safe for Common Procedures
TUESDAY, Feb. 26, 2019 -- Overlapping surgery is not associated with differences in in-hospital mortality or complication rates but is linked to increased surgery length, according to a study published in the Feb. 26 issue of the Journal of the...
https://ift.tt/2IByJnb
Converting Naloxone to OTC Expected to Increase Sales
TUESDAY, Feb. 26, 2019 -- The demand for naloxone is relatively inelastic with respect to changes in its out-of-pocket price, and conversion to an over-the-counter medication is expected to increase naloxone pharmacy sales, according to a study...
https://ift.tt/2Tp7ocd
Contributors to Delay of Multiple Sclerosis Diagnosis ID'd
TUESDAY, Feb. 26, 2019 -- First symptoms and disease type are contributors to delays in multiple sclerosis (MS) diagnosis, according to a study recently published in the Multiple Sclerosis Journal. Laura Barin, from the University of Zurich, and...
https://ift.tt/2ICVsPN
Glaucoma Burden Increasing Globally but Not Equally
TUESDAY, Feb. 26, 2019 -- The health burden of glaucoma increased globally in the past 25 years and is distributed unequally, according to a study published online Feb. 20 in Acta Ophthalmologica. Wei Wang, from Sun Yat-Sen University in Guangzhou,...
https://ift.tt/2Tp7nFb
The Development and Application of Virtual Reality Animation Simulation Technology: Take Gastroscopy Simulation System as an Example
Abstract
Virtual reality (VR) technology has a great potential in the field of medical simulation due to its immersion, interactivity and autonomy. It provides a new direction for integration and application in various disciplines. Combination of VR technology and clinical practice brings great convenience for medical education and experiments. Modern VR simulators can create realistic environments that capture minute anatomical details with high accuracy and solves the problem of difficulty in mass productions with traditional devices. Taking gastroscopy simulation system as an example, this paper discusses the development and application of VR animation technology, together with its excellent performance and current research status in surgery, scientific research, training and education.
https://ift.tt/2NuERfH
Analysing blood from intraosseous access: a systematic review
Intraosseous (IO) access is used widely as an optional vascular route for critically ill patients. It is still unclear whether the IO access can be used as a source for emergency blood samples. The aim of this study was to systematically review the existing literature on the usability of IO blood samples for analysing the parameters relevant to emergency care. We performed a data search from the Medline and Embase databases, the Cochrane Library and the Clinical trials registry. Animal studies and studies with healthy and ill adults and children were included in the search. The data were collected and reported following the PRISMA guidelines. The PROSPERO database registration number of this review is CRD42017064194. We found 27 studies comparing the blood samples from the IO space with arterial or venous samples, but only three of them followed the recommended guidelines for method comparison studies. The study populations were heterogeneous, and the sample sizes were relatively small (14, 17 and 20 individuals) in the three studies. The results of specific laboratory parameters were scarce and discordant. The evidence on the agreement between IO and arterial and venous samples is still weak. Existing studies with healthy volunteers and animal models provide important insight into the analyses of IO samples, but more evidence, especially from haemodynamically unstable patients, is needed for wider implementation of IO blood sampling in critically ill patients.https://ift.tt/2SpNF7u
Cerebrospinal fluid/blood glucose point-of-care testing ratio for diagnosing bacterial meningitis in a limited medical resource setting
No abstract availablehttps://ift.tt/2XmM1Y9
The prevalence of unexplained falls and syncope in older adults presenting to an Irish urban emergency department
Aim There is growing evidence of an overlap between unexplained falls and syncope in older adults. Our aim was to examine the prevalence and associated resource utilization of these conditions in an urban emergency department (ED). Patients and methods A single-centre, prospective, observational study was carried out over a 6-month period. Consecutive patients older than 50 years who presented to the ED because of a fall, collapse or syncope were included. Univariate analysis of demographic data is presented as percentages, mean (SD), 95% confidence intervals (CIs) and medians (interquartile range). Logistic regression modelling was used to examine the association between falls and resource utilization. Results A total of 561 patients fulfilled the inclusion criteria during the study period. Unexplained fallers accounted for 14.3% (n=80; 95% CI: 13.3–15.3) and syncope for 12.7% (n=71; 95% CI: 11.7–13.6) of all fall presentations. Overall, 50% (n=282; 95% CI: 48.20–52.34) of patients required admission to hospital. Patients with syncope [odds ratio (OR)=2.48, 95% CI: 1.45–4.23], and unexplained falls (OR=2.36, 95% CI: 1.37–4.08) were more likely to require admission than those with an explained falls. Unexplained fallers were nearly five times more likely to suffer recurrent falls (OR=4.97, 95% CI: 2.89–8.56). Conclusion One in four older fallers presenting to ED have symptoms suggestive of syncope or an unexplained fall. There are significant biological consequences of recurrent falls including greater rates of cognitive decline, gait and mobility disturbances, depression and frailty. Recognition that syncope can present as an unexplained fall in older adults is important to ensure that appropriate early modifiable interventions are initiated.https://ift.tt/2XpKctn
Are on-scene blood transfusions by a helicopter emergency medical service useful and safe? A multicentre case–control study
Introduction In the prehospital setting, crystalloid fluids are frequently used, but only erythrocytes are capable of transporting oxygen to tissues. The aim of this study was to establish the efficacy and safety of the prehospital use of uncross matched type O rhesus-negative packed red blood cells (URBC) by the Dutch physician-staffed helicopter emergency medical service. We hypothesized that prehospital URBC transfusions are safe and more effective with respect to survival than resuscitations with crystalloids. Methods The effects of prehospital URBC transfusions were studied by comparing a cohort of patients (>18 years) who were treated with a combination of URBC and crystalloid fluids with a matched control group of patients who received crystalloid fluids alone. Results Among 73 adults who received prehospital URBC transfusions, 50 (68%) patients were included. No transfusion reactions were observed. No effect of prehospital transfusion on 24-h or 30-day survival was found. Haemoglobin levels at presentation to the emergency department were higher in the URBC cohort. The two groups had similar cumulative erythrocyte requirements within the first 24 h. Conclusion Neither survival benefits nor a decreased incidence of shock on admission were observed after prehospital helicopter emergency medical service URBC transfusions. There were no prehospital transfusion reactions in this study; therefore, URBC transfusions were deemed to be safe. A prospective randomized study is warranted to evaluate the effect of early URBC transfusions and transfusions with preheated URBC on the survival of patients with severe prehospital haemorrhagic shock.https://ift.tt/2SvM7Jc
Performance of a quick pregnancy test on whole blood in early pregnancy units: a prospective cohort study
Objective To assess the diagnostic performance of the NG-Test human chorionic gonadotropin (hCG) WB, which is a new point-of-care (POC) hCG whole-blood test. Materials and methods This prospective study included women consulted in early pregnancy units for vaginal bleeding and/or pelvic pain with unknown pregnancy status after medical consultation including a pelvic ultrasound scan. A new POC test (the NG-Test hCG WB) and the usual laboratory serum test (considered the gold standard) were performed in patients. The results were interpreted in a blinded manner. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the NG-Test hCG WB. Results During the study period, 200 patients were included. The pregnancy rate was 17%. For the laboratory test, with a 5 UI/l hCG positivity threshold, the sensitivity, specificity, PPV, NPV, and Youden index of the NG-Test hCG WB were 89.7, 100, 100, 97.9, and 0.90%, respectively. Considering a 10 UI/l hCG positivity threshold, test sensitivity, specificity, PPV, NPV, and Youden index were 96.3, 100, 100, 99.3, and 0.96%, respectively. False-negative cases were either extremely brief pregnancies or residual hCG after miscarriage. The result was obtained within 5 min with the NG-Test hCG WB versus 90±31 min with the laboratory test. It was easy to use. Conclusion The NG-Test hCG WB showed a high sensitivity, specificity, PPV, and NPV. Its use as triage in the case of a negative pelvic ultrasound exam is a potential strategy to improve patient flow, with an average time saving of 85 min.https://ift.tt/2Sx4EFa
Investigating the effects of under-triage by existing major incident triage tools
Objectives Triage is a key principle in the effective management of a major incident. Its effectiveness is a balance between identifying those in need of life-saving intervention, and those triaged incorrectly as either needing/not needing a life-saving intervention. The primary aim of this study was to report mortality in those under-triaged by existing major incident triage tools. Secondary aims were to report the ability of triage tools at identifying serious injury by body region (defined as an Abbreviated Injury Scale severity score≥3). Patients and methods Retrospective database analysis of the UK Trauma Audit Research Network for all adult patients (≥18 years) between 2006 and 2014. Patients were defined as priority one using a previously published list. Using the first recorded hospital physiology, patients were categorized by the Modified Physiological Triage Tool (MPTT), National Ambulance Resilience Unit (NARU) Sieve and the Major Incident Medical Management and Support (MIMMS) Triage Sieve. Categorical and continuous data were analyzed using a χ2-test and Mann–Whitney U-test respectively. Results During the study period, 218 985 adult patients met the Trauma Audit Research Network inclusion criteria, with 24 791 (19.5%) priority one patients, of which 70% were male with a median age of 51 (33–71) years and injury severity score of 16 (9–25). The MPTT showed the lowest rate of under-triage (42.4%, Phttps://ift.tt/2SpNGs4
Rapid cardiothoracic ultrasound protocol for diagnosis of acute heart failure in the emergency department
Objectives The aim of this study was to evaluate the performance of a rapid cardiothoracic ultrasound protocol (CaTUS), combining echocardiographically derived E/e' and lung ultrasound (LUS), for diagnosing acute heart failure (AHF) in patients with undifferentiated dyspnea in an emergency department (ED). Patients and results We enrolled 100 patients with undifferentiated dyspnea from a tertiary care ED, who all had CaTUS done immediately upon arrival in the ED. CaTUS was positive for AHF with an E/e' > 15 and congestion, that is bilateral B-lines or bilateral pleural fluid, on LUS. In addition, an inferior vena cava index was also recorded to analyze whether including a central venous pressure estimate would add diagnostic benefit to the CaTUS protocol. All 100 patients had a brain natriuretic peptide (BNP) sample withdrawn, and 96 patients underwent chest radiography in the ED, which was analyzed later by a blinded radiologist. The reference diagnosis of AHF consisted of either a BNP of more than 400 ng/l or a BNP of less than 100 ng/l in combination with congestion on chest radiography and structural heart disease on conventional echocardiography. CaTUS had a sensitivity of 100% (95% confidence interval: 91.4–100%), a specificity of 95.8% (95% confidence interval: 84.6–99.3%), and an area under the curve of 0.979 for diagnosing AHF (Phttps://ift.tt/2XqayLW
Monitoring measles outbreaks using emergency department data in France
No abstract availablehttps://ift.tt/2Spu9Ip
The utility of clinical ultrasonography in identifying distal forearm fractures in the pediatric emergency department
Objective The aim of this study is to evaluate the utility of Point-Of-Care Ultrasound (POCUS) for diagnosing distal forearm fractures in pediatric emergency departments (ED). Patients and methods A prospective observational study was carried out in children aged younger than 15 years attended in an ED with an indication of radiography because of a suspected distal forearm fracture. The POCUS was performed considering cortical irregularity or disruption compatible with fracture. Then, the radiography was requested and the patient was evaluated by an ED traumatologist. Both tests were blinded to each other. The radiograph was considered to be the reference diagnostic test. Diagnostic validation tests were performed. Results A total of 115 patients [mean age: 9.1 (SD: 3.1) years; 50.4% males] were included, with 57 of these presenting fractures: 42 (73.7%) single bone fractures and 15 (26.3%) combined fractures of the radius and ulna. As such, 72 fractures were detected (prevalence 31.3%). The sensitivity and specificity of POCUS for detecting fractures were 94.4% [95% confidence interval (CI): 86.4–98.5] and 96.8% (95% CI: 92.8–99.0), respectively. The positive and negative predictive values were 93.2% (95% CI: 84.7–97.7) and 97.5% (95% CI: 93.6–99.3), respectively. Conclusion POCUS enables the clinical diagnosis of distal forearm fractures in ED. In addition, this is a highly accurate technique that can be applied easily by the ED pediatrician. As such, its inclusion as part of the physical examination could improve the accuracy of the clinical diagnosis and the global management of the patient.https://ift.tt/2Sq7bAJ
Response to ‘Lung ultrasound for the diagnosis of pneumonia’
No abstract availablehttps://ift.tt/2SpAnYJ
Changes in Efficiency and Quality of Nursing Electronic Health Record Documentation After Implementation of an Admission Patient History Essential Data Set
https://ift.tt/2BYaARX
Effect of Preoperative Video Information on Anxiety and Satisfaction in Patients Undergoing Abdominal Surgery
https://ift.tt/2U5YOMw
Implementation of Structured Documentation and Standard Nursing Statements: Perceptions of Nurses in Acute Care Settings
https://ift.tt/2BPRZr1
Development and Evaluation of the Automated Risk Assessment System for Catheter-Associated Urinary Tract Infection
https://ift.tt/2U4ECdM
Spatial Dose Patterns Associated with Radiation Pneumonitis in a Randomized Trial Comparing Intensity-Modulated Radiation Therapy with Passive Scattering Proton Therapy for Locally Advanced Non-Small Cell Lung Cancer
We explored spatial dose patterns associated with symptomatic radiation pneumonitis (RP) in patients with non-small-cell lung cancer given either intensity-modulated photon therapy or passive scattering proton therapy. A dose distribution analysis highlighted regional dose differences associated with both RP status and treatment modality, showing that regions spared with protons are complementary to those correlated with RP; these results can be useful for clinical practice and for designing future trials to minimize RP.
https://ift.tt/2Exxxgl
Efficacy and risk of cytotoxic chemotherapy in extensive disease-small cell lung cancer patients with interstitial pneumonia
Abstract
Background
Small cell lung cancer (SCLC) is characterized by a high propensity for metastases and a poor prognosis irrespective of high sensitivity for initial chemotherapy. Although interstitial pneumonia (IP) is one of risk factors for lung cancer, efficacy of cytotoxic chemotherapy for patients with SCLC with IP remains unclear. Our study aims to evaluate the efficacy of systemic chemotherapy and assess risk of acute exacerbation (AE)-IP with cytotoxic drugs for extensive disease (ED)-SCLC patients with IP.
Methods
We performed a retrospective study of 192 consecutive ED-SCLC patients with IP (n = 40) and without IP (n = 152) between 2008 and 2016.
Result
31 of 40 ED-SCLC patients with IP and 130 of 152 patients without IP received systemic chemotherapy. The efficacy of chemotherapy in patients with IP was not inferior to that in patients without IP (overall survival [OS], 7.1 [95% confidence interval (CI): 0.2–14.0] vs. 10.0 [95% CI: 8.2–11.8] months, P = 0.57). Pretreatment serum levels of lactate dehydrogenase (LDH; 651.7 ± 481.0 vs. 301.4 ± 110.7 U/mL, P = 0.01) and C-reactive protein (CRP; 8.9 ± 9.6 vs. 1.8 ± 1.8 U/mL, P = 0.008) were correlated with developed AE-IP in the ED-SCLC patients with IP.
Conclusion
Systemic chemotherapy was effective even in ED-SCLC patients with IP. However, the risk of developed AE-IP that was high in patients with IP and should be evaluated using serum LDH and CRP levels before initial chemotherapy.
https://ift.tt/2U8XqIR
Breakthrough cancer pain in patients with abdominal visceral cancer pain
To assess the characteristics of breakthrough cancer pain (BTcP) in patients with abdominal cancer pain, and the eventual factors associated with its presentation.
https://ift.tt/2IOkPxU
Sequence of acquisition of self-management skills to follow a gluten-free diet by adults with celiac disease
Celiac disease (CD) treatment is lifelong adherence to a gluten-free diet (GFD), requiring mastery of numerous skills to maintain health.
https://ift.tt/2EAdIVR
Off-Label Drugs in Neonatology: Analyses Using Large Data Bases
Two reports in this volume of The Journal from the neonatology team at the University of North Carolina use the Pediatrix Medical Group Data Warehouse of administrative information to further the ongoing discussion of the frequent off-label uses of drugs in the neonatal intensive care unit (NICU).1,2 The report on the frequent, but not approved, use of furosemide for bronchopulmonary dysplasia (BPD) identified that prolonged use can decrease BPD.1 The report on surfactant for preterm infants with or at risk of respiratory distress syndrome (RDS) identified frequent deviations from the Food and Drug Administration (FDA) approved uses.
https://ift.tt/2H4vS3N
Are High Lumbar Punctures Safe? An MRI Morphometric Study of the Conus Medullaris
A high lumbar puncture (LP) at L2‐L3 or above is often necessary to consider on technical grounds, but complications of conus medullaris (CM) damage during high LP are potentially concerning. We hypothesized that a high LP might be safer than previously thought, by accounting for movements of the CM upon patient positional changes. We retrospectively reviewed standard normal supine lumbar spine MRIs of 58 patients, and used electronic calipers on axial images at the T12‐L1, L1‐2, and L2‐3 disc levels to measure the transverse diameter of the CM relative to the size of the dorsal thecal sac space (DTSS) through which a spinal needle could be inserted. On 142 axial images, the means for CM diameters were 8.2 mm, 6.0 mm, and 2.9 mm at the three levels, respectively. We then used known literature mean CM displacement values in the legs flexed and unflexed lateral decubitus positions (LDP), to factor in CM shifts to the dependent side. We found that at all three levels, the likely positional shift of the CM would be too small and insufficient to displace the entire CM out of the DTSS. However, if needle placement could be confined to the midsagittal plane, an LP in the unflexed LDP would theoretically be entirely safe at both L1‐L2 and L2‐L3, and almost so at L2‐L3 in the legs flexed LDP. Thus, high LPs at L1‐L2 and L2‐3 are in theory likely safer than considered previously, more so in the legs unflexed than in the flexed LDP.
This article is protected by copyright. All rights reserved.
https://ift.tt/2Xmk9TQ
Consistency of the Lateral Canthus as an Anatomic Landmark and its Clinical Implications
Purpose
Successful oculofacial procedures require the availability of a reliable surgical and anatomic landmark. This study aimed to determine the usefulness of the lateral canthus as a surface landmark.
Methods
Seventy‐seven from 42 Korean cadavers were dissected. The horizontal distance from the lateral canthus to the lateral orbital margin and the vertical distances from the zygomaticofrontal suture and the inferior orbital margin to the lateral canthus were measured.
Results
The mean horizontal distance from the lateral canthus to the lateral orbital margin was 7.8 mm. Although the horizontal position of the lateral canthus appears to alter with age, the variation was only 2–3 mm. The mean vertical distances from the zygomaticofrontal suture and inferior orbital margin to the lateral canthus were 8.1 and 17.2 mm. The vertical position of the lateral canthus did not vary with age, being located inferiorly within a fingernail width from the zygomaticofrontal suture
Conclusion
The lateral canthus, which is easily accessible and supported by muscular and fibrous lateral orbital attachments, exhibits small anatomic variations. Thus the lateral canthus could act as a reliable surface landmark for identifying the location of underlying structures and describing a lesion on the face.
This article is protected by copyright. All rights reserved.
https://ift.tt/2SoPq4U
The influence of treatment sequence in the prognostic value of TMPRSS2‐ERG as biomarker of taxane resistance in castration‐resistant prostate cancer
TMPRSS2‐ERG expression in blood has been correlated with low docetaxel benefit in metastatic castration‐resistant prostate cancer (mCRPC). This multicentre study aimed to prospectively asses its role as a taxane‐resistance biomarker in blood and retrospectively in tumours, exploring also the impact of prior abiraterone/enzalutamide (A/E) in patients and in vitro. TMPRSS2‐ERG was tested by quantitative reverse‐transcription PCR. We included 204 patients (137 blood and 124 tumour samples) treated with taxanes. TMPRSS2‐ERG expression was correlated with prostate‐specific antigen (PSA)‐progression‐free survival (PFS), radiological‐PFS (RX‐PFS), and overall survival (OS). Independent association with survival was evaluated by multivariate Cox modelling. In vitro ERG knockdown and combinatorial and sequential experiments with enzalutamide and docetaxel were performed in VCaP cells. Prior A/E (HR 1.8, 95%CI 1.2‐2.8) and blood TMPRSS2‐ERG detection (HR 2, 95%CI 1.1‐3.7) were independently associated to lower PSA‐PFS. In patients without prior A/E, blood and tumour TMPRSS2‐ERG independently predicted lower PSA‐PFS (HR 3.3, 95%CI 1.4‐7.9 and HR 1.8, 95%CI 1.02‐3.3, respectively) to taxanes. When prior A/E was administered, TMPRSS2‐ERG was not associated with outcome. There was a significant interaction between blood TMPRSS2‐ERG and prior A/E related to PSA‐PFS (P=0.032) and RX‐PFS (P=0.009). In vitro stable ERG inhibition did not sensitize VCaP cells to docetaxel. Concomitant enzalutamide and taxanes were synergistic, but prior enzalutamide reduced docetaxel cytotoxicity in VCaP cells. Enzalutamide induced the expression of neuroendocrine markers and reduced that of E‐cadherin. We conclude that prior hormone‐therapy may influence taxanes response and TMPRSS2‐ERG prognostic value. Thus, multiple and sequential biomarkers are needed in CRPC follow‐up evaluation.
This article is protected by copyright. All rights reserved.
https://ift.tt/2H4LQuA
Cachexia‐related long noncoding RNA, CAAlnc1, suppresses adipogenesis by blocking the binding of HuR to adipogenic transcription factor mRNAs
Cancer‐associated cachexia (CAC) is a devastating syndrome characterized by progressive losses of adipose tissue and skeletal muscle. CAC‐related adipose tissue loss (CAL) occurs early and is associated with a shorter survival time. To explore potential regulatory long non‐coding RNAs (lncRNAs) of CAL, RNA microarrays were used to analyze the transcriptomes of white adipose tissue from CAC mice versus control mice. A set of differentially expressed lncRNAs was identified, and among them was CAAlnc1, which suppressed adipogenesis of C3H10 cells as demonstrated by gain‐of‐function and loss‐of‐function experiments. RNA immunoprecipitation and pull‐down assays revealed Hu antigen R (HuR) was an important binding partner of CAAlnc1. The interaction between CAAlnc1 and HuR blocked the binding of HuR to adipogenic transcription factor mRNAs and further downregulated the expression of these transcription factors. This study generated a list of CAL‐related lncRNAs and provided details of a functional lncRNA which may play an important role in CAL.
This article is protected by copyright. All rights reserved.
https://ift.tt/2H3blws
CA125 over‐release behavior following a 75‐gram oral glucose test as a predictive biomarker of multidrug resistance in patients with ovarian cancer
Multidrug resistance is a major cause of death in patients with ovarian cancer. To improve patient survival, we developed a novel, noninvasive and convenient tool, the 75‐gram oral glucose (75gOG)‐stimulated CA125 test, to monitor cancer chemoresistance in real time. Our in vitro proof‐of‐principal experiments revealed that post‐75gOG glucose and insulin peaks can synergistically increase cancer‐derived CA125 levels, and the increase in CA125 secretion (ΔCA125) is correlated with the overactivation of the insulin receptor (IR)‐PI3K‐Akt axis and increases (ΔIC50s) in cisplatin/taxol IC50s. Correspondingly, among the 93 patients enrolled, post‐75gOG CA125 over‐release (i.e., enhanced ΔCA125) behavior was associated with overexpression of the IR‐PI3K‐Akt pathway and its downstream components, namely, IR, pAkt, pS6 and GLUT4, in cancer specimens. Furthermore, both pre‐ and postsurgical 75gOG CA125 tests demonstrated that CA125 over‐release showed excellent prediction efficacy on the chemoresistance potential of ovarian cancer; notably, the former indicated the need for an optimal debulking surgery, and the latter suggested the use of IR‐PI3K‐Akt inhibitors. Both test results possess independent prognostic significance for the 2‐year progression‐free survival (PFS) and overall survival (OS) of patients. The odds ratios and corresponding 95% confidence intervals (95% CIs) were 2.680 (95% CI: 1.393‐5.156) for patients with CA125 over‐release behavior evidenced by a presurgical 75gOG CA125 test or 3.822 (95% CI: 1.942‐7.522) for that evidenced by a postsurgical test in PFS; and 3.320 (95% CI: 1.508‐7.309) for patients with CA125 over‐release behavior evidenced by a presurgical test or 5.212 (95% CI: 2.241‐12.121) for that evidenced by a postsurgical test in OS.
This article is protected by copyright. All rights reserved.
https://ift.tt/2tDUzMv
CUL7 promotes cancer cell survival through promoting Caspase‐8 ubiquitination
The Cullin 7 (CUL7) gene encodes a member of the cullin family of E3 ubiquitin ligases. Accumulated evidence suggests that CUL7 is oncogenic. However, the mechanism by which CUL7 improves cancer cell survival has not been fully elucidated. Here, we reported that CUL7 confers anti‐apoptotic functions by interacting with Caspase‐8. CUL7 prevents Caspase‐8 activation by promoting Caspase‐8 modification with non‐degradative polyubiquitin chains at K215. CUL7 knockdown sensitized cancer cells to TRAIL‐induced apoptosis in vitro and in nude mice. These results suggest that CUL7 limits extrinsic apoptotic signaling by promoting Caspase‐8 ubiquitination.
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https://ift.tt/2H2Lkxm
A bottom-up summarization algorithm for videos in the wild
Video summarization aims to provide a compact video representation while preserving the essential activities of the original video. Most existing video summarization approaches relay on identifying important f...
https://ift.tt/2IEUW3T
Response suppression produces a switch-cost for spatially compatible saccades
Abstract
Executive function supports the rapid alternation between tasks for online reconfiguration of attentional and motor goals. The oculomotor literature has found that a prosaccade (i.e., saccade to veridical target location) preceded by an antisaccade (i.e., saccade mirror symmetrical to a target) elicits an increase in reaction time (RT), whereas the converse switch does not. This switch-cost has been attributed to the antisaccade task's requirement of inhibiting a prosaccade (i.e., response suppression) and transforming a target's coordinate (i.e., vector inversion)—executive processes thought to contribute to a task-set inertia that proactively interferes with the planning of a subsequent prosaccade. It is, however, unclear whether response suppression and vector inversion contribute to a task-set inertia or whether the phenomenon relates to a unitary component (e.g., response suppression). Here, the same stimulus-driven (SD) prosaccades (i.e., respond at target onset) as used in previous work were used with minimally delayed (MD) prosaccades (i.e., respond at target offset) and arranged in an AABB paradigm (i.e., A = SD prosaccade, B = MD prosaccade). MD prosaccades provide the same response suppression as antisaccades without the need for vector inversion. RTs for SD task-switch trials were longer and more variable than their task-repeat counterparts, whereas values for MD task-switch and task-repeat trials did not reliably differ. Moreover, SD task-repeat and task-switch movement times and amplitudes did not vary and thus demonstrate that a switch-cost is unrelated to a speed accuracy trade-off. Accordingly, results suggest the executive demands of response suppression is sufficient to engender the persistent activation of a non-standard task-set that selectively delays the planning of a subsequent SD prosaccade.
https://ift.tt/2T2DNph
Using Sniper-Cas9 to Minimize Off-target Effects of CRISPR-Cas9 Without the Loss of On-target Activity Via Directed Evolution
Here, we present a protocol to optimize CRISPR-Cas9 to achieve a higher specificity without the loss of on-target activity. We use a directed evolution approach called Sniper-screen to find a mutant Cas9 with the desired characteristics. Sniper-Cas9 is compatible with truncated single-guide RNAs and delivery in a ribonucleoprotein format, well-known strategies for achieving higher specificities.
https://ift.tt/2EwWb0D
Assessment of Ultrastructural Neuroplasticity Parameters After In Utero Transduction of the Developing Mouse Brain and Spinal Cord
https://ift.tt/2VljT5J
Large Area Substrate-Based Nanofabrication of Controllable and Customizable Gold Nanoparticles Via Capped Dewetting
This protocol details a novel nano-manufacturing technique that can be used to make controllable and customizable nanoparticle films over large areas based on the self-assembly of dewetting of capped metal films.
https://ift.tt/2ExiEut
Factors affecting the chemical efficacy of 2% sodium hypochlorite against oral steady‐state dual‐species biofilms: exposure time and volume application
Abstract
Aim
To study the influence of time and volume of 2% sodium hypochlorite (NaOCl) on biofilm removal and to investigate the changes induced on the biofilm architecture. Steady‐state, dual‐species biofilms of standardised thickness and a realistic contact surface area between biofilms and NaOCl were used.
Methodology
Streptococcus oralis J22 and Actinomyces naeslundii T14V‐J1 biofilms were grown on saliva‐coated hydroxyapatite discs within sample holders in the Constant Depth Film Fermenter (CDFF) for 96 h. Two percent NaOCl was statically applied for three different time intervals (60, 120 and 300 s) and in two different volumes (20 and 40 μl) over the biofilm samples. The diffusion‐driven effects of time and volume on biofilm disruption and dissolution were assessed with Optical Coherence Tomography (OCT). Structural changes of the biofilms treated with 2% NaOCl were studied with Confocal Laser Scanning Microscopy (CLSM) and Low Load Compression Testing (LLCT). A two‐way analysis of variance (2‐way ANOVA) was performed, enabling the effect of each independent variable as well as their interaction on the outcome measures.
Results
OCT showed that by increasing the exposure time and volume of 2% NaOCl, both biofilm disruption and dissolution significantly increased. Analysis of the interaction between the two independent variables revealed that by increasing the volume of 2% NaOCl, significant biofilm dissolution could be achieved in less time. Examination of the architecture of the remaining biofilms corroborated the EPS‐lytic action of 2% NaOCl, especially when higher volumes were applied. The viscoelastic analysis of the 2% NaOCl‐treated biofilms revealed that the preceding application of higher volumes could impact their subsequent removal.
Conclusions
Time and volume of 2% NaOCl application should be taken into account for maximizing the anti‐biofilm efficiency of the irrigant and devising targeted disinfecting regimes against remaining biofilms.
This article is protected by copyright. All rights reserved.
https://ift.tt/2Tj08yn
The effect of scalp cooling on CIA-related quality of life in breast cancer patients: a systematic review
Abstract
Purpose
Chemotherapy-induced alopecia (CIA) remains a distressing adverse event of cancer treatment but may be prevented by scalp cooling. The effectiveness of scalp cooling, however, is dependent on the chemotherapy regimen with successful hair preservation (i.e., < 50% hair loss) in 41–59% of women on taxane-based therapies in comparison to 16–36% on anthracycline-based therapies. Despite the potential utility, use of scalp cooling has shown a more equivocal impact on quality of life (QoL). In this review, we aim to evaluate the use of scalp cooling for CIA and quantitative QoL measures.
Methods
A systematic review of PubMed, Embase, Web of Science, and Cochrane databases for clinical studies on scalp cooling to prevent CIA published before October 29, 2018 was performed. Clinical studies with 5 or more patients that reported on a quantitative QoL measure were included and graded according to a modified five-point scale from the Oxford Centre for Evidence-Based Medicine.
Results
Studies meeting inclusion criteria included 4 randomized clinical trials (RCT), 8 cohort studies, and 1 cross-sectional study with 1282 unique patients. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30: 46%) and Breast Cancer Module (QLQ-BR23: 46%) represented the most commonly used QoL assessments. Overall, 4 (31%) of the 13 studies concluded that scalp cooling was associated with significant improvements in QoL measures; 8 (62%) determined that there was either non-significant or no improvements; and 1 (7.7%) provided a mixed conclusion. Although 2 (50%) RCT demonstrated that scalp cooling can effectively prevent CIA depending on the chemotherapy regimen, these studies did not show that successful hair preservation was associated with improved QoL measures.
Conclusions
This review demonstrates that scalp cooling is not consistently associated with significant QoL improvements as assessed by EORTC QLQ-C30 and -BR23. Representing a critical limitation, more than one-third of the studies did not subcategorize QoL outcomes for successfully or unsuccessfully scalp-cooled patients but rather reported on QoL measures for all scalp-cooled patients in general. Failure to prevent hair loss in patients undergoing an expensive and potentially uncomfortable treatment likely contributes to decreased well-being, impacting the overall distribution of QoL measures in scalp cooling patients compared to controls. Future studies should incorporate validated QoL instruments specific to hair disease and classify QoL outcomes for scalp-cooled patients based on the degree of hair preservation.
https://ift.tt/2IDAhwY
Planar cell polarity protein Dishevelled 3 (Dvl3) regulates ectoplasmic specialization (ES) dynamics in the testis through changes in cytoskeletal organization
Planar cell polarity protein Dishevelled 3 (Dvl3) regulates ectoplasmic specialization (ES) dynamics in the testis through changes in cytoskeletal organization
Planar cell polarity protein Dishevelled 3 (Dvl3) regulates ectoplasmic specialization (ES) dynamics in the testis through changes in cytoskeletal organization, Published online: 26 February 2019; doi:10.1038/s41419-019-1394-7
Planar cell polarity protein Dishevelled 3 (Dvl3) regulates ectoplasmic specialization (ES) dynamics in the testis through changes in cytoskeletal organizationhttps://ift.tt/2UaSCma
Chronic lymphocytic leukemia (CLL) treatment: So many choices, such great options
Within a period of just over a decade, managing chronic lymphocytic leukemia (CLL) has become more effective and yet more challenging than ever before. The important improvement in the treatment of CLL can be ascribed to the availability of many new options, mainly with the development of novel targeted therapies, such as ibrutinib, idelalisib, duvelisib and venetoclax. There are now newer tests that reliably define high‐risk patients, and treatment plans can be tailored accordingly. Overall, this indeed is a new era in the treatment of patients with CLL. However, despite this progress, CLL remains an incurable disease and continues to remain challenging. In this brief review, the authors highlight the many great choices available to clinicians who manage patients with CLL and focus on the sequencing of these choices based on the available data.
https://ift.tt/2IB23dv
Most gene fusions in cancer are stochastic events
Abstract
Cancer‐associated gene fusions resulting in chimeric proteins or aberrant expression of one or both partner genes are pathogenetically and clinically important in several hematologic malignancies and solid tumors. Since the advent of different types of massively parallel sequencing (MPS), the number of identified gene fusions has increased dramatically, prompting the question whether they all have a biologic impact. By ascertaining the chromosomal locations of 8,934 genes involved in 10,861 gene fusions reported in the literature, we here show that there is a highly significant association between gene content of chromosomes and chromosome bands and number of genes involved in fusions. This strongly suggests that a clear majority of gene fusions detected by MPS are stochastic events associated with the number of genes available to participate in fusions and that most reported gene fusions are passengers without any pathogenetic importance.
This article is protected by copyright. All rights reserved.
https://ift.tt/2TiqtMN
Rogaratinib: A potent and selective pan‐FGFR inhibitor with broad antitumor activity in FGFR‐overexpressing preclinical cancer models
Aberrant activation in fibroblast growth factor signaling has been implicated in the development of various cancers, including squamous cell lung cancer, squamous cell head and neck carcinoma, colorectal and bladder cancer. Thus, fibroblast growth factor receptors (FGFRs) present promising targets for novel cancer therapeutics. Here, we evaluated the activity of a novel pan‐FGFR inhibitor, rogaratinib, in biochemical, cellular and in vivo efficacy studies in a variety of preclinical cancer models. In vitro kinase activity assays demonstrate that rogaratinib potently and selectively inhibits the activity of FGFRs 1, 2, 3, and 4. In line with this, rogaratinib reduced proliferation in FGFR‐addicted cancer cell lines of various cancer types including lung, breast, colon and bladder cancer. FGFR and ERK phosphorylation interruption by rogaratinib treatment in several FGFR‐amplified cell lines suggests that the anti‐proliferative effects are mediated by FGFR/ERK pathway inhibition. Furthermore, rogaratinib exhibited strong in vivo efficacy in several cell line‐ and patient‐derived xenograft models characterized by FGFR overexpression. The observed efficacy of rogaratinib strongly correlated with FGFR mRNA expression levels. These promising results warrant further development of rogaratinib and clinical trials are currently ongoing (ClinicalTrials.gov Identifiers: NCT01976741, NCT03410693, NCT03473756).
This article is protected by copyright. All rights reserved.
https://ift.tt/2EpzlHl
Mechanisms Underlying Gut Hormone Secretion Using the Isolated Perfused Rat Small Intestine
Here, we present a powerful and physiological model to study the molecular mechanisms underlying gut hormone secretion and intestinal absorption — the isolated perfused rat small intestine.
https://ift.tt/2tE6Mkd
Atypical Temporal Work Patterns Linked to Depressive Symptoms
TUESDAY, Feb. 26, 2019 -- Women working extra-long hours and men and women working weekends have increased depressive symptoms, according to a study published online Feb. 25 in the Journal of Epidemiology & Community Health. Gillian Weston, from...
https://ift.tt/2XrP8hw
Excessive Gestational Weight Gain Tied to Maternal Morbidity
TUESDAY, Feb. 26, 2019 -- Gestational weight gain in excess of guidelines from the Institute of Medicine (IOM) is associated with increased risk of severe maternal morbidity, according to a study published in the March issue of Obstetrics &...
https://ift.tt/2Spnf5O
Environmental Exposures Before, After Birth Tied to Lung Function
TUESDAY, Feb. 26, 2019 -- Exposure to several chemicals before and after birth appears to be associated with a decrease in lung function later in childhood, according to a study published in the February issue of The Lancet Planetary Health. Lydiane...
https://ift.tt/2Xqgapm
MRI Cardiac Stress Test Predicts Death From Heart Disease
TUESDAY, Feb. 26, 2019 -- Stress cardiac magnetic resonance imaging (CMR) can predict mortality in patients with known or suspected coronary artery disease (CAD), according to a study published online Feb. 8 in JAMA Cardiology. John F. Heitner,...
https://ift.tt/2Spne1K
Program Aids Weight Loss in Patients With Mental Illness
TUESDAY, Feb. 26, 2019 -- A behavioral weight loss intervention is effective among overweight and obese individuals with serious mental illness (SMI), regardless of their diabetes status, according to a study published online Feb. 14 in Diabetes...
https://ift.tt/2XrP7Ku
Ultrasound of Calcaneus Efficient for Screening Bone Health
TUESDAY, Feb. 26, 2019 -- Ultrasonography (US) of the calcaneus is efficient for screening bone health, according to a study published in the March issue of the Journal of the American Osteopathic Association. Carolyn Komar, Ph.D., from the West...
https://ift.tt/2SpncHa
Prediction Rule IDs Febrile Infants 0 to 2 Months Old at Low Risk for SBIs
TUESDAY, Feb. 26, 2019 -- A new prediction rule can accurately identify febrile infants aged ≤60 days at low risk for serious bacterial infections (SBIs) using urinalysis, absolute neutrophil count (ANC), and procalcitonin levels, according to a...
https://ift.tt/2Xqg7da
Classroom Initiative Ups Participation in School Breakfast
TUESDAY, Feb. 26, 2019 -- A breakfast-in-the-classroom initiative increases participation in the federal School Breakfast Program but has an unintended consequence of increasing the incidence and prevalence of obesity, according to a study published...
https://ift.tt/2SpnbD6
Sertraline Tops CBT for Reducing Depression in Dialysis Patients
TUESDAY, Feb. 26, 2019 -- For patients receiving maintenance hemodialysis, an engagement interview on treatment acceptance has no effect on acceptance of depression treatment, and depression scores are modestly better with sertraline treatment...
https://ift.tt/2Xqg6G8
Long-term outcomes and prognostic factors of pulmonary metastasectomy for osteosarcoma and soft tissue sarcoma
Abstract
Background
The prognostic factors of pulmonary metastasectomy in patients with osteosarcoma and soft tissue sarcoma remain controversial. The purpose of our analysis was to explore the prognostic factors and outcomes of patients with osteosarcoma and soft tissue sarcoma who underwent pulmonary metastasectomy at our institution.
Methods
We reviewed the data of 44 patients who underwent resection of pulmonary metastases from 1996 to 2016 at our institution. The Kaplan–Meier method, log-rank test and multivariate Cox hazard model were used for comparison and survival analyses.
Results
There was no perioperative mortality. The median post-metastasectomy overall survival was 24.8 months, and the 5-year overall survival rate of all patients was 43.5%. The 5-year survival rate of the patients who underwent repeat thoracotomies was 60.0%. Incomplete resection, a largest tumor size > 2 cm and a disease-free interval < 12 months were associated with poor survival in multivariate analyses. Among eight patients, who underwent repeat pulmonary resection, two remain alive with no evidence of disease. These patients had the longest DFI and DFI-2 (time from first pulmonary metastasectomy to the diagnosis of recurrent pulmonary metastasis), respectively.
Conclusion
The survival of patients with a relatively long disease-free interval, small tumor size and complete resection was favorable following the treatment of osteosarcoma and soft tissue sarcoma with pulmonary metastasectomy. Repeat pulmonary metastasectomies also provide favorable prognosis in select patients.
https://ift.tt/2tFHJgQ
First-line therapy-stratified survival in BRAF-mutant melanoma: a retrospective multicenter analysis
Abstract
Background
Inhibition of the mitogen-activated protein kinase (MAPK) pathway as well as programmed death 1 receptor (PD-1) blockade was shown to prolong overall survival (OS) in patients with advanced B-Raf proto-oncogene (BRAF)-mutant melanoma. However, due to the lack of head-to-head trials, it remains unclear if one of these therapeutic approaches should be preferred in first-line therapy. Here, we present a retrospective analysis comparing anti-PD-1 monotherapy with BRAF/MAPK/ERK kinase (MEK) combined inhibition used as first-line agents in a real-world clinical setting.
Patients and methods
Clinical data, routine blood counts and lactate dehydrogenase (LDH) levels of 301 patients with unresectable or metastatic melanoma harboring an activating mutation in BRAF (V600E/K) were included. Of these, 106 received anti-PD-1 antibodies, while 195 patients were treated with a selective BRAF inhibitor combined with an MEK inhibitor as palliative first-line therapy. Patients were sub-grouped according to previously described predictive and prognostic markers.
Results
OS was significantly longer in patients receiving anti-PD-1 monotherapy compared to patients receiving combined MAPK inhibitors. Subsequent therapies were comparable among these groups. The difference in OS was less pronounced in patients with high LDH levels and visceral metastatic spread.
Conclusion
First-line treatment with a PD-1 blocking antibody might be associated with longer OS than first-line inhibition of the MAPK pathway in patients with advanced melanoma harboring mutant BRAF. These hypothesis-generating data need to be confirmed or rejected in prospective, randomized trials.
https://ift.tt/2Nw4Bs3
Expression of a soluble IL-10 receptor enhances the therapeutic effects of a papillomavirus-associated antitumor vaccine in a murine model
Abstract
The presence of IL-10, produced either by tumor cells or immunosuppressive cells, is frequently associated with a poor prognosis for cancer progression. It may also negatively impact anticancer treatments, such as immunotherapies, that otherwise would promote the activation of cytotoxic T cells capable of detecting and destroying malignant cells. In the present study, we evaluated a new adjuvant approach for anticancer immunotherapy using a plasmid vector encoding a soluble form of the IL-10 receptor (pIL-10R). pIL-10R was coadministered to mice with a DNA vaccine encoding the type 16 human papillomavirus (HPV-16) E7 oncoprotein genetically fused with glycoprotein D of herpes simplex virus (HSV) (pgDE7h). Immunization regimens based on the coadministration of pIL-10R and pgDE7h enhanced the antitumor immunity elicited in mice injected with TC-1 cells, which express HPV-16 oncoproteins. The administration of the DNA vaccines by in vivo electroporation further enhanced the anticancer effects of the vaccines, leading to the activation of tumor-infiltrating polyfunctional E7-specific cytotoxic CD8+ T cells and control of the expansion of immunosuppressive cells. In addition, the combination of immunotherapy and pIL-10R allowed the control of tumors in more advanced growth stages that otherwise would not be treatable by the pgDE7h vaccine. In conclusion, the proposed treatment involving the expression of IL-10R enhanced the antitumor protective immunity induced by pgDE7h administration and may contribute to the development of more efficient clinical interventions against HPV-induced tumors.
https://ift.tt/2GNJJMl
Depression in inflammatory bowel disease: risk factor, prodrome or extraintestinal manifestation?
We read with interest Frolkis and colleagues' recent study, in which depression was associated with increased risk of incident IBD in a large primary care database.1 While treatment of depression in IBD has been suggested to improve IBD outcomes,2 this study goes further, suggesting that assertive pharmacological treatment of depression could reduce the incidence of IBD altogether.
Despite the study's manifest strengths, we wish to draw the authors' attention to an important limitation of its current design that tempers its conclusions. Temporality between exposure and outcome is a key test of causality.3 This is challenging in the context of depression and IBD because their symptoms frequently overlap. For example, 40% to 80% of patients with established IBD experience significant levels of fatigue and sleep disturbance,4 and such symptoms frequently arise during the prodromal period prior to IBD onset.5 Although the authors...
https://ift.tt/2tG5ipz
Reducing the number of surveillance colonoscopies with faecal immunochemical tests
We read with interest the article by Cross et al,1 which examined the use of FIT in intermediate risk patients undergoing 3 yearly surveillance colonoscopies. The investigators assessed the diagnostic accuracy of this approach, together with the number of advanced adenomas and colorectal cancers missed, and the potential cost savings.
The results indicate that replacing 3 yearly colonoscopy with annual FIT (with a positivity threshold of 40 µg Hb/g faeces) would result in cost savings over the screening cycle of £4.7 million reflecting an 87% reduction in colonoscopies. However, such an approach would miss up to 41% of interval cancers and 67% of advanced adenomas. Modelling a lower FIT positivity threshold (10 µg Hb/g faeces) suggests that the strategy would reduce colonoscopies by 71% but would still miss 28% of cancers and 43% of advanced adenomas. Regardless of the financial savings, such a clinical outcome is likely to be deemed unacceptable. In addition to...
https://ift.tt/2H8Z5ua
LncRNA HOXA-AS2 Facilitates Tumorigenesis and Progression of Papillary Thyroid Cancer by Modulating the miR-15a-5p/HOXA3 Axis
Human Gene Therapy, Ahead of Print.
https://ift.tt/2tESaBm
Questions Answered and Unanswered by the First CRISPR Editing Study in a Canine Model of Duchenne Muscular Dystrophy
Human Gene Therapy, Ahead of Print.
https://ift.tt/2tDjWxM
Classification and regression tree-based prediction of 6-mercaptopurine-induced leucopenia grades in children with acute lymphoblastic leukemia
Abstract
Purpose
The rationale of the current study was to develop 6-mercaptopurine (6-MP)-mediated hematological toxicity prediction model for acute lymphoblastic leukemia (ALL) therapeutic management.
Methods
A total of 96 children with ALL undergoing therapy with MCP-841 protocol were screened for all the ten exons of TPMT, exon 2, exon 3 and intron 2 of ITPA using bidirectional sequencing. This dataset was used to construct prediction models of leucopenia grade by constructing classification and regression trees (CART) followed by smart pruning.
Results
The developed CART model indicated TPMT*12 and TPMT*3C as the key determinants of toxicity. TPMT int3, int4 and int7 polymorphisms exert toxicity when co-segregated with one mutated allele of TPMT*12 or TPMT*3C or ITPA exon 3. The developed CART model exhibited 93.6% accuracy in predicting the toxicity. The area under the receiver operating characteristic curve was 0.9649.
Conclusions
TPMT *3C and TPMT*12 are the key determinants of 6-MP-mediated hematological toxicity while other variants of TPMT (int3, int4 and int7) and ITPA ex2 interact synergistically with TPMT*3C or TPMT*12 variant alleles to enhance the toxicity. TPMT and ITPA variants cumulatively are excellent predictors of 6-MP-mediated toxicity.
https://ift.tt/2SuczTo
Noninvasive Monitoring of Lesion Size in a Heterologous Mouse Model of Endometriosis
https://ift.tt/2SZKubG
Lung Tumor Cell Recruitment Assay
This manuscript describes a method to quantify tumor cell accumulation in the lungs in an animal model of tumor metastasis.
https://ift.tt/2EhM7Yf
Clonotypic diversity of the T-cell receptor corroborates the immature precursor origin of cutaneous T-cell lymphoma
Purpose: Mycosis fungoides (MF) is one of the most common types of extranodal T-cell lymphomas, considered to be caused by malignant transformation of the mature T-cell residing in the skin. However, some clinical observations such as the multifocal distribution of MF lesions or patterns of relapse after radiotherapy are not readily explainable by the mature T-cell origin theory. Experimental Design: We have performed a detailed analysis of T-cell receptor (TCR) rearrangements in single malignant cells and in biopsies from MF tumors composed of >80% of malignant cells using next-generation sequencing (NGS) to pinpoint the relationship between neoplastic cells in MF. We have also aimed to detect malignant, circulating T-cell by whole blood TCR sequencing. Results: We found a substantial clonal heterogeneity in the MF samples with regards to TCR, and we demonstrated that lymphoma cells harboring identical TCR sequences may harbor different TCRα and β sequences. Lack of absolute TCRα, -β, - monoclonality was further confirmed by TCR amplification and sequencing from microdissected lymphoma cells. We have also found the TCR rearrangements characteristic for lymphoma cells in patients' peripheral blood despite lack of leukemic blood involvement, however the circulating TCR clonotype did not always represent the dominant cutaneous clonotype. Conclusions: These findings can be explained by a model where malignant transformation takes place during early T-cell development giving rise to circulating pre-malignant clones which home to the skin producing clinically apparent lesions of cutaneous lymphoma. Therapeutic strategies in T-cell lymphoma should therefore target those early lymphoma precursor cells.
https://ift.tt/2NvbtpJ
Radiomics on gadoxetic acid-enhanced magnetic resonance imaging for prediction of postoperative early and late recurrence of single hepatocellular carcinoma
Purpose: To evaluate the usefulness of the radiomic model in predicting early (≤2 years) and late (>2 years) recurrence after curative resection in cases involving a single hepatocellular carcinoma (HCC) 2-5 cm in diameter using preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI), in comparison to the clinicopathologic model. Experimental design: This retrospective study included 167 patients with surgically resected and pathologically confirmed single HCC 2-5cm in diameter (n = 167, training set:validation set = 128:39) who underwent preoperative gadoxetic acid-enhanced MRI between January 2010 and December 2015. A radiomic model, a clinicopathologic model, and a combined clinicopathologic-radiomic (CCR) model were built using a random survival forest to predict disease-free survival (DFS) in the following conditions: early DFS vs. late DFS, dynamic phases, and the peritumoral area included in the segmentation. Results: The radiomic model showed a prognostic performance comparable to the clinicopathologic model only with 3 mm peritumoral border extension (c-index difference [radiomic-clinicopathologic], -0.021, P = 0.758). The CCR model with the 3 mm border extension showed the highest c-index value but no statistically significant improvement over the clinicopathologic model (CCR, 0.716 [0.627-0.799]; clinicopathologic model, 0.696 [0.557-0.799]). Conclusion: The prognostic value of the preoperative radiomic model with 3 mm border extension showed comparable performance to that of the postoperative clinicopathologic model for predicting DFS of early recurrence of HCC using gadoxetic acid-enhanced MRI. This suggests the importance of including peritumoral changes in the radiomic analysis of HCC.
https://ift.tt/2GLzhoH
Plasma HER2 (ERBB2) copy number predicts response to HER2-targeted therapy in metastatic colorectal cancer
Purpose: ERBB2 (HER2) amplification is an emerging biomarker in colon cancer, conferring sensitivity to combination anti-HER2 therapy. Measurement of HER2 copy number is typically performed using surgical specimens, but cell-free circulating tumor DNA (ctDNA) analysis may be a non-invasive alternative. We determined the sensitivity of pCN for detecting ERBB2 amplifications and whether plasma copy number (pCN) correlated with tissue-detected copy number. We also assessed response to HER2-targeted therapy based on pCN and suggest a pCN threshold predictive of response. Experimental Design: Forty-eight pre-treatment and progression plasma samples from 29 HER2-positive patients in the HERACLES A clinical trial were tested using the Guardant360™ cfDNA assay. We correlated ERRB2 pCN with progression-free survival (PFS) and best objective response (BOR) and applied an adjustment method based on tumor DNA shedding using the maximum mutant allele fraction as a surrogate for tumor content to accurately determine the pCN threshold predictive of response. Results: 47/48 samples had detectable ctDNA and 46/47 samples were ERBB2-amplified based on cfDNA (2.55-122 copies; 97.9% sensitivity (95% CI = 87.2-99.8%). An adjusted ERBB2 pCN of ≥25.82 copies correlated with BOR and PFS (p=0.0347). Conclusions:cfDNA is a viable alternative to tissue-based genotyping in the metastatic setting. The cfDNA platform utilized correctly identified 28/29 (96.6%) of pre-treatment samples as ERBB2-amplified and predicted benefit from HER2-targeted therapy. In this study, an observed pCN of 2.4 and an adjusted pCN of 25.82 copies of ERBB2 is proposed to select patients who will benefit from HER2-targeted therapy.
https://ift.tt/2Nw4ywn
Large-scale circulating microRNA profiling for the liquid biopsy of prostate cancer
Purpose: The high false-positive rate of prostate-specific antigen (PSA) may lead to unnecessary prostate biopsies. Therefore, the United States Preventive Services Task Force recommends that decisions regarding PSA-based screening of prostate cancer (PCa) should be made with caution in men aged 55-69 years, and that men ≥70 years should not undergo PSA screening. Here, we investigated the potential of serum microRNAs (miRNAs) as an accurate diagnostic method in patients with suspected prostate cancer (PCa). Experimental Design:Serum samples of 809 patients with PCa, 241 negative prostate biopsies, and 500 patients with other cancer types were obtained from the National Cancer Center, Japan. Forty-one healthy control samples were obtained from two other hospitals in Japan. Comprehensive microarray analysis was performed for all samples. Samples were divided into three sets. Candidate miRNAs for PCa detection were identified in the discovery set (n=123). A diagnostic model was constructed using combinations of candidate miRNAs in the training set (n=484). The performance of the diagnostic model was evaluated in the validation set (n=484). Results: In the discovery set, 18 candidate miRNAs were identified. A robust diagnostic model was constructed using the combination of two miRNAs (miR-17-3p and miR-1185-2-3p) in the training set. High diagnostic performance with a sensitivity of 90% and a specificity of 90% was achieved in the validation set regardless of the Gleason score and clinical TNM stage. Conclusions: The model developed in the present study may help improve the diagnosis of PCa and reduce the number of unnecessary prostate biopsies.
https://ift.tt/2GRxsa3
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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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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
