Occlusive renovascular disease presents a vexing challenge. Hypertension induced by renal artery stenosis is among the most widely studied and well-characterized causes of secondary hypertension. When arterial occlusion reaches critical levels, renal blood flow decreases and kidney function eventually deteriorates. It seems intuitive that restoring vessel patency and blood flow should provide clinical benefits both for relieving hypertension and preserving kidney function. This principle was widely accepted in the days of renovascular surgery (mainly in the 1970s) and after wider application of endovascular angioplasty and stenting (in the 1990s).
http://ift.tt/2qGeom5
Σάββατο 20 Μαΐου 2017
Evidence and Renovascular Disease: Trials and Mistrials?
Preparation and anticancer activity evaluation of an amorphous drug nanocomposite by simple heat treatment
http://ift.tt/2rD8Zu1
Bortezomib pharmacokinetics in tumor response and peripheral neuropathy in multiple myeloma patients receiving bortezomib-containing therapy
http://ift.tt/2rDprKO
Baicalin inhibits human osteosarcoma cells invasion, metastasis, and anoikis resistance by suppressing the transforming growth factor-β1-induced epithelial-to-mesenchymal transition
http://ift.tt/2rDto24
Isatin inhibits SH-SY5Y neuroblastoma cell invasion and metastasis through MAO/HIF-1α/CXCR4 signaling
http://ift.tt/2rDqcn9
MicroRNA-148a promotes apoptosis and suppresses growth of breast cancer cells by targeting B-cell lymphoma 2
http://ift.tt/2rDsG4Z
Protein kinase B: emerging mechanisms of isoform-specific regulation of cellular signaling in cancer
http://ift.tt/2rDlBkO
Activation of a c-Jun N-terminal kinase-mediated autophagy pathway attenuates the anticancer activity of gemcitabine in human bladder cancer cells
http://ift.tt/2rDCjkj
The aurora kinase inhibitor AMG 900 increases apoptosis and induces chemosensitivity to anticancer drugs in the NCI-H295 adrenocortical carcinoma cell line
http://ift.tt/2rDjpde
Pseudolaric acid B induces endometrial cancer Ishikawa cell apoptosis and inhibits metastasis through AKT-GSK-3β and ERK1/2 signaling pathways
http://ift.tt/2rDDTTc
Weekly paclitaxel after first-line failure in patients with advanced non-small-cell lung cancer: everyday clinical practice in a single centre
http://ift.tt/2rDDPD0
Oxytocin inhibits head and neck squamous cell carcinoma cell migration by early growth response-1 upregulation
http://ift.tt/2rDrzSY
The incidence of radiation necrosis following stereotactic radiotherapy for melanoma brain metastases: the potential impact of immunotherapy
http://ift.tt/2rDn1Mp
Cardiac Amyloidosis: Diagnosis and Treatment Strategies
Abstract
Cardiac amyloidosis in the United States is most often due to myocardial infiltration by immunoglobulin protein, such as in AL amyloidosis, or by the protein transthyretin, such as in hereditary and senile amyloidosis. Cardiac amyloidosis often portends a poor prognosis especially in patients with systemic AL amyloidosis. Despite better understanding of the pathophysiology of amyloid, many patients are still diagnosed late in the disease course. This review investigates the current understanding and new research on the diagnosis and treatment strategies in patients with cardiac amyloidosis. Myocardial amyloid infiltration distribution occurs in a variety of patterns. Structural and functional changes on echocardiography can suggest presence of amyloid, but CMR and nuclear imaging provide important complementary information on amyloid burden and the amyloid subtype, respectively. While for AL amyloid, treatment success largely depends on early diagnosis, for ATTR amyloid, new investigational agents that reduce production of transthyretin protein may have significant impact on clinical outcomes. Advancements in the non-invasive diagnostic detection and improvements in early disease recognition will undoubtedly facilitate a larger proportion of patients to receive early therapy when it is most effective.
http://ift.tt/2qFttUT
Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study
Abstract
Observational studies have shown an association between obesity and venous thromboembolism (VTE) but it is not known if observed associations are causal, due to reverse causation or confounding bias. We conducted a Mendelian Randomization study of body mass index (BMI) and VTE. We identified 95 single nucleotide polymorphisms (SNPs) that have been previously associated with BMI and assessed the association between genetically predicted high BMI and VTE leveraging data from a previously conducted GWAS within the INVENT consortium comprising a total of 7507 VTE cases and 52,632 controls of European ancestry. Five BMI SNPs were associated with VTE at P < 0.05, with the strongest association seen for the FTO SNP rs1558902 (OR 1.07, 95% CI 1.02–1.12, P = 0.005). In addition, we observed a significant association between genetically predicted BMI and VTE (OR = 1.59, 95% CI 1.30–1.93 per standard deviation increase in BMI, P = 5.8 × 10−6). Our study provides evidence for a causal relationship between high BMI and risk of VTE. Reducing obesity levels will likely result in lower incidence in VTE.
http://ift.tt/2qFBtFB
Invasive lobular carcinoma with extracellular mucin production—a novel pattern of lobular carcinomas of the breast. Clinico-pathological description of eight cases
Abstract
Invasive lobular carcinoma of the breast is known to produce intracellular mucin and has been recognized in single-case reports to show extracellular mucin production, as well. This latter morphology is not only rare but must also be under- or misdiagnosed. The aim was to better characterize this entity. Cases of lobular cancers demonstrating extracellular mucin formation were identified in a multi-institutional effort and their clinical and morphologic features were assessed. Immunohistochemistry was used to characterize the E-cadherin-membrane complex, neuroendocrine differentiation, and to some extent, mucin formation. All but one of the eight cases occurred in postmenopausal patients. Extracellular mucin production was present in 5 to 50% of the tumour samples and rarely also appeared in nodal and distant metastases. The tumours were completely E-cadherin negative and showed cytoplasmic p120 positivity. The majority (n = 6/8) was also completely negative for β-catenin, but two tumours displayed focal β-catenin positivity in the mucinous area. MUC1 and MUC2 expression was observed in all and 7/8 tumours, respectively; neuroendocrine differentiation was present in only one. Invasive lobular carcinoma with extracellular mucin formation is a rare morphologic variant of lobular carcinoma prone to be misdiagnosed and warranting further studies.
http://ift.tt/2rD1Qdd
Immunogenomics: using genomics to personalize cancer immunotherapy
Abstract
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy. A T cell-dependent mechanism of cancer progression was discovered in 2012, providing a potential link to cancer immunotherapy. Since then, an antibody against cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), ipilimumab, and three programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, pembrolizumab (Keytruda), nivolumab (Opdivo), and atezolizumab (Tecentriq), were approved by the Food and Drug Administration (FDA) in the USA. In this review article, based on evidence that has been emerging in the literature over the last decade, we will discuss the basis for including genomic data in immunotherapy regimens, the current progress in identifying biomarkers targetable by immune checkpoint blockade, and the application of these therapies in modern oncology programs. Going forward, the clinical application of NGS in personalized oncology programs could include dose monitoring and adjustment or the development of individualized vaccines or other personalized therapies based on the mutational landscape. The continued identification of new neoantigens and the efficient mobilization of tumor-reactive lymphocytes in patients with cancer will promote the advancement of immunotherapy using personalized NGS-guided technologies.
http://ift.tt/2rDL8JK
A prospective randomized study comparing three different approaches to fluoroscopy-guided shoulder arthrography according to the experience of practitioners
Abstract
Objective
To compare three approaches via the anterior and posterior glenohumeral joints, and the rotator interval in fluoroscopy-guided shoulder arthrography according to the experience of the practitioners.
Materials and methods
This prospective randomized study was originally designed to have 34 subjects for each approach, and finally evaluated 98 patients (mean age: 51.5 years; 55 men) from July to December 2014, who had shoulder arthrography via the anterior (n = 41) or posterior glenohumeral joint (n = 27) approaches, or via the rotator interval approach (n = 30) by residents (n=76) or fellows (n=22). The success rate, number of punctures, fluoroscopy time, radiation dose, and complications of the three methods were compared, and according to the practitioners.
Results
The success rate was 100% for the anterior glenohumeral joint approach (34 out of 34), 90.0% for the posterior glenohumeral joint approach (23 out of 30), and 88.2% for the rotator interval approach (30 out of 34; p = 0.013). There was no difference in the success rate according to the practitioners' experience. Fluoroscopy time was longest for the posterior glenohumeral joint approach (mean: 95.44 s) and shortest for the rotator interval approach (mean: 31.57 s, p = 0.006). Radiation dose was larger by 1st- or 2nd-year residents (p = 0.014), with no difference among the three approaches. Only one patient who underwent arthrography using the posterior glenohumeral joint approach complained about post-procedural pain.
Conclusion
Fluoroscopy-guided shoulder arthrography via the posterior glenohumeral joint or rotator interval approach may be difficult for trainees, and the posterior glenohumeral joint approach may need a long fluoroscopy time.
http://ift.tt/2qCiLhz
Small, superficial, indeterminate soft-tissue lesions as suspected sarcomas: is primary excision biopsy suitable?
Abstract
Objective
Suspected soft-tissue sarcomas are typically investigated using magnetic resonance imaging (MRI), with a view to planning image-guided core needle biopsy for confirmation of the histological diagnosis. Indeterminate superficial lesions may be small and therefore potentially difficult to biopsy safely, such lesions possibly being more amenable to primary excision biopsy. The aim of this study is to determine the suitability of this practice in the setting of a specialist sarcoma service.
Materials and methods
All patients referred over a 12-month period to the sarcoma service with a small (<3-cm), indeterminate, superficial soft-tissue mass according to MRI criteria, or a small lesion of the hand or foot deemed unsafe for percutaneous biopsy, and who underwent primary excision biopsy were included. The histology results were categorized into neoplastic and non-neoplastic lesions, and assessed for resection completeness.
Results
Fifty-eight patients fulfilled the inclusion criteria from all patients referred to the sarcoma service in a 12-month period. Of these, 42 out of 58 (72.4%) had benign neoplasms, 4 out of 58 (6.9%) had malignant tumours, 2 out of 58 (3.4%) an intermediate grade lesion, while 10 out of 58 (17.2%) were non-neoplastic. All 4 malignant lesions were completely excised at the time of excision biopsy.
Conclusions
Primary excision biopsy of small, indeterminate soft-tissue masses within the setting of a specialist sarcoma service is a suitable management option. Only a small proportion of small superficial soft-tissue lesions with indeterminate MRI features are malignant tumours.
http://ift.tt/2q799Ij
Therapeutic outcome of CT-guided radiofrequency ablation in patients with osteoid osteoma
Abstract
Objective
To assess the long-term outcome of computed tomography-guided radiofrequency ablation (CT-guided RFA) in patients with suspected osteoid osteoma (OO).
Materials and methods
Single-center retrospective study. Patients with clinical suspicion and imaging diagnosis of osteoid osteoma were treated by CT-guided RFA using the same device with either a 7- or 10-mm active tip electrode. Specific precautions were applied in case of articular or spinal OO. Patients were contacted by phone to evaluate the long-term outcome in terms of pain, ability to perform daily activities (including sports), and long-term complications. Success was defined as the absence of residual pain and ability to perform daily activities normally.
Results
From 2008 to 2015, 126 patients were treated by CT-guided RFA for OO in our institution. Mean patient age was 26.1 years (SD = 11, range 1–53); mean delay to diagnosis was 16.9 months (SD = 15.2, range 1–120). Among patients who answered the follow-up call (n = 88), the overall success rate was 94.3%: 79/88 (89.8%) had primary success of the procedure, and 4/88 (4.5%) had a secondary success (repeat-RFA after pain recurrence). Mean follow-up time was 34.6 months (SD = 24.7, range 3–90). Few complications occurred: two mild reversible peripheral nerve injuries, one brachial plexus neuropathy, one broken electrode tip fragment, and one muscular hematoma.
Conclusion
Osteoid osteoma can be effectively and safely treated by CT-guided RFA using the presented ablation protocol. Beneficial effects of the treatment persist at long-term follow-up.
http://ift.tt/2qCl58e
Acute calcific tendinopathy of the popliteus tendon: a rare case diagnosed using a multimodality imaging approach and treated conservatively
Abstract
Acute calcific tendinopathy of the popliteus tendon is a rare medical entity associated with significant patient discomfort. We present the case of a previously healthy 48-year-old female who presented to the emergency department with acute onset of left knee pain. Initial radiographs revealed calcifications within the posterolateral compartment of the knee. Ultrasound imaging demonstrated a swollen and hypoechoic popliteus tendon with an increased color Doppler signal at the periphery of the tendon as well as calcification in the tendon and adjacent soft tissues. Subsequently performed MRI revealed a thickened and heterogeneous popliteus tendon near its femoral attachment with marked edematous changes surrounding the tendon. Local ultrasound-guided glucocorticoid injection had successful clinical results with no recurrence at 8-month follow-up. In this case report we review the literature for similar previously reported cases. This case report of popliteus tendon calcific tendinopathy provides comprehensive multimodality imaging findings and a description of its non-surgical management.
http://ift.tt/2q79kmW
Periosteal mesenchymal chondrosarcoma of the tibia with multifocal bone metastases: a case report
Abstract
Mesenchymal chondrosarcoma of bone is a rare high-grade variant of chondrosarcoma, which typically has central intramedullary location. The tumor is characterized by admixture of highly anaplastic small round malignant cells and islands of mineralized low-grade hyaline cartilage. It is most unusual for this tumor to arise on the surface of a long bone. We describe a patient with periosteal mesenchymal chondrosarcoma that arose at the surface of the right tibia with multifocal bone metastases. Radiographic, CT, MRI, and PET-CT features of this unusual tumor are presented.
http://ift.tt/2q7gW93
MRI guided needle localization in a patient with recurrence pleomorphic sarcoma and post-operative scarring
Abstract
MRI-guided wire localization is commonly used for surgical localization of breast lesions. Here we introduce an alternative use of this technique to help with surgical resection of a recurrent pleomorphic sarcoma embedded in extensive post-treatment scar tissue. We describe a case of recurrent pleomorphic soft tissue sarcoma in the thigh after treatment with neoadjuvant therapy, surgery, and radiation. Due to the distortion of the normal tissue architecture and formation of extensive scar tissue from prior treatment, wire localization under MRI was successfully used to assist the surgeon in identifying the recurrent tumor for removal.
http://ift.tt/2qCstAp
Evaluating the Procedure for Performing Awake Cystometry in a Mouse Model
http://ift.tt/2r3DZ9l
Loss of L- Selectin Guided CD8+ but not CD4+ Cells, Protects Against Ischemia Reperfusion Injury in a Steatotic Liver
Abstract
Background & Aims: Steatotic liver responds with increased hepatocellular injury when exposed to an ischemic-reperfusion insult. Increasing evidence supports the role of immune cells as key mediators of this injury in a normal (lean) state, but data about their role in a steatotic liver are practically non-existent. The objective of the current study was to delineate contribution of specific phenotypes of T cells and adhesion molecules in exacerbated cell death in steatotic liver injury. Methods: RNA sequencing was performed on isolated steatotic primary hepatocytes and T cell markers were assessed in hepatic lymphocytes after ischemia reperfusion injury (IRI) in high fat diet (HFD) fed mice. CD8-/- and CD4-/- mice along with CD8 and L-selectin antibody treated mice were fed on a HFD and hepatocellular injury was assessed by histology, propidium iodide injection and ALT after IRI. Results: RNA sequencing demonstrated a strikingly differential gene profile in steatotic hepatocytes vs. lean hepatocytes. After injury, the HFD liver showed increased necrosis, infiltrating CD8+ cells, ALT and proinflammatory cytokines. Hepatic lymphocytes demonstrated increased CD8+/CD62L+(L-selectin) cells in HFD fed mice after IRI. CD8-/- mice and CD8 depleted C57BL/6 mice, demonstrated significant protection from injury, which was not seen in CD4-/- mice. L-selectin blockade also demonstrated significant hepatoprotection from IRI. L selectin ligand MECA-79 was increased in HFD fed mice undergoing IRI. Conclusion: Blockade of CD8 and L-selectin but not CD4, ameliorated hepatocellular injury, confirming that CD8+ cells are critical drivers of injury in a steatotic liver. This represents a novel therapeutic target in steatotic liver injury, underlining the importance of development of therapies specific to a steatotic liver. This article is protected by copyright. All rights reserved.
http://ift.tt/2rDGDzb
Cancers, Vol. 9, Pages 53: Physical Activity and Quality of Life in Cancer Survivors: A Meta-Synthesis of Qualitative Research
Qualitative research on the impact of physical activity on quality of life (QoL) in adults diagnosed with cancer is accumulating. However, the field of physical activity and cancer survivorship lack a synthesis of this research to reliably understand the implications for future research and practice. The aim of this meta-synthesis was to identify, appraise, and synthesize qualitative research on cancer survivors' perspectives of the impact of physical activity on their QoL. Seven electronic databases were searched for original studies published in English, and reference lists of relevant studies were hand-searched to identify additional studies. Forty studies met eligibility criteria and were included in this meta-synthesis. Study characteristics and major findings were extracted, and findings were summarized, compared, and synthesized. Themes identified in this review revealed that physical activity positively impacted four dimensions of cancer survivors' QoL: physical (e.g., managing the physical consequences of cancer and its treatment), psychological (e.g., evoking positive self-perceptions), social (e.g., feeling understood by others), and spiritual (e.g., redefining life purpose). This meta-synthesis corroborates conclusions from reviews of quantitative research and illustrates that physical activity can be used to improve QoL in adult cancer survivors, regardless of diagnosis (i.e., stage, cancer type) and treatment status. It also provides detailed insight into specific aspects within each dimension of QoL impacted by physical activity from cancer survivors' perspectives, which is important for understanding the meaning and utility of physical activity for them. However, more research is needed to further develop the qualitative evidence base in order to better understand how physical activity impacts on QoL experiences in men, young adults, and adults diagnosed with less common types of cancer at different points along cancer trajectory (i.e., diagnosis, treatment, post-treatment, palliation).
http://ift.tt/2qBSAYn
DNA topoisomerase-targeting chemotherapeutics: what’s new?
Abstract
To resolve the topological problems that threaten the function and structural integrity of nuclear and mitochondrial genomes and RNA molecules, human cells encode six different DNA topoisomerases including type IB enzymes (TOP1 and TOP1mt), type IIA enzymes (TOP2α and TOP2β) and type IA enzymes (TOP3α and TOP3β). DNA entanglements and the supercoiling of DNA molecules are regulated by topoisomerases through the introduction of transient enzyme-linked DNA breaks. The covalent topoisomerase–DNA complexes are the cellular targets of a diverse group of cancer chemotherapeutics, which reversibly stabilize these reaction intermediates. Here we review the structure–function and catalytic mechanisms of each family of eukaryotic DNA topoisomerases and the topoisomerase-targeting agents currently approved for patient therapy or in clinical trials, and highlight novel developments and challenges in the clinical development of these agents.
http://ift.tt/2qEyQDQ
Egg White or Sun-Kissed: A Cross-Cultural Exploration of Skin Color and Women’s Leisure Behavior
Abstract
The present study explores how culture-based meanings and values toward skin color, which are associated with women's body image ideals and gender-role expectations, profoundly influence women's leisure behaviors. Using in-depth interviews with East Asian, Asian American, and Euro-American women (n = 43), results revealed how leisure behaviors are tied to cultural perceptions of skin color. People from different cultural backgrounds construct meanings and values pertaining to skin color, including beauty-related standards, social class, gender roles, and lifestyles. Culture-based values, such as the preference for tanned skin among Euro-Americans and for lighter skin among East Asians, affect a wide range of daily behaviors. These behaviors include conscious as well as subtle daily decision-making regarding sun-seeking, sun-avoidance, and sun-protection behaviors; indoor versus outdoor leisure participation; and appearance modifications. The study's results add knowledge to how perceptions and attitudes toward skin color and appearance manifest in women's daily behavior in general and leisure behavior in particular. In addition, the current study shows how individual behaviors reflect cultural meanings and values toward body image, specifically skin color, by emphasizing the links between cultural values and women's day-to-day lives.
http://ift.tt/2r2VXJo
Herpes simplex virus glycoprotein D targets a specific dendritic cell subset and improves the performance of vaccines to human papillomavirus-associated tumors.
| Related Articles |
Herpes simplex virus glycoprotein D targets a specific dendritic cell subset and improves the performance of vaccines to human papillomavirus-associated tumors.
Mol Cancer Ther. 2017 May 18;:
Authors: Porchia BFMM, Moreno ACR, Ramos RN, Diniz MO, de Andrade LHTM, Rosa DS, Barbuto JAM, Boscardin SB, Ferreira LCS
Abstract
Cervical cancer is a major public health problem and one of the leading causes of cancer deaths in women. Virtually all cases of cervical cancer, as well as a growing share of anal and head/neck tumors, are associated with human papillomavirus (HPV) infection. Despite the effectiveness, the available prophylactic vaccines do not benefit women with cervical lesions or cancer. Therefore, the search of new immunotherapeutic approaches to treat HPV-induced tumors is still a priority. The present study characterizes a therapeutic antitumor vaccine based on the genetic fusion of the Herpes simplex virus-1 (HSV-1) glycoprotein D (gD) with the E7 oncoprotein from HPV-16 (gDE7). Two subcutaneous doses of gDE7, admixed with poly (I:C), conferred complete and long lasting therapeutic antitumor protection to mice previously challenged with tumor cells expressing the HPV-16 oncoproteins. The vaccine induced multifunctional E7-specific CD8(+) T cells with cytotoxic activity and effector memory phenotype (CD44(+) CD62L(low)). Additionally, gDE7 admixed with poly (I:C) vaccination controlled the expansion of tumor-induced regulatory T cells and myeloid-derived suppressor cells (MDSCs). More importantly, gDE7 activated mouse CD11c(+) CD8α(+) and human BDCA3(+) dendritic cells (DCs), specialized in antigen cross-presentation to CD8(+) T cells, under in vitro conditions. These results indicated that the activation of a specific DC population, mediated by gD, improved the antigen-specific immune responses and the therapeutic performance induced by antitumor vaccines. These results open perspectives for the clinical testing of gDE7-based vaccines under the concept of active immunization as a tool for the therapeutic control of cancer.
PMID: 28522585 [PubMed - as supplied by publisher]
http://ift.tt/2rC4C2p
Reference values for some clinical, hematobiochemical and electrocardiographic parameters in miniature donkeys: the effect of sex, age and season
Abstract
In the current study, we aimed to establish reference values for the most important clinical, hematobiochemical and electrocardiographic (ECG) parameters and evaluate the effect of sex, age and season in miniature donkey. We hypothesized that these parameters in this valuable breed of donkey would be different from those of other species of equidae. Twenty apparently healthy miniature donkeys aged 1–8 years and weighing averagely 115 ± 10 kg, with an average height of 0.83 ± 0.3 m, were used in this study. Based on sex, age and season of sampling, the animals were divided into groups. Animals less than 2 years old, between 2 and 5 years old and those over 5 years of age were considered foal, young and adult, respectively. The ECG was attached as a bipolar base-apex lead and indices measured and analyzed were P, QRS and T wave amplitude and duration and duration of PR, QT and RR intervals. Red blood cell (RBC), white blood cell (WBC) and WBC differential counts were performed using a hemacytometer. Sera were collected for measurement of sodium (Na+), potassium (K+), chloride (Cl−), calcium (Ca2+), magnesium (Mg2+) and phosphorus (P−) concentrations. Heart rate (HR), PR and RR intervals were different from reference ranges. Male and female animals showed no significant differences in clinical, hematobiochemical and ECG parameters except in serum concentrations of Ca2+ and Mg2+(P < 0.05). There were significant differences in HR, RR interval and serum level of P− and Na+ among age groups. Eosinophil in autumn was significantly higher than that in spring (P < 0.05). The configuration of P and T waves was mainly biphasic and monophasic, respectively. The majority of ECGs was of the QS configuration. Differences between sexes and seasons and among age groups were insignificant (P > 0.05). The data obtained in the present study are the first reference values to be published for the miniature donkey and can be useful in our understanding of this breed's normal parameters, which will help veterinarians to appropriately interpret laboratory data. Results of the present study can be used for monitoring the health status, diagnosing the diseases and improving the management and conservation strategies of this breed.
http://ift.tt/2qBDbHn
MUG-Mel2, a novel highly pigmented and well characterized NRAS mutated human melanoma cell line.
| Related Articles |
MUG-Mel2, a novel highly pigmented and well characterized NRAS mutated human melanoma cell line.
Sci Rep. 2017 May 18;7(1):2098
Authors: Rinner B, Gandolfi G, Meditz K, Frisch MT, Wagner K, Ciarrocchi A, Torricelli F, Koivuniemi R, Niklander J, Liegl-Atzwanger B, Lohberger B, Heitzer E, Ghaffari-Tabrizi-Wizsy N, Zweytick D, Zalaudek I
Abstract
NRAS mutation in melanoma has been associated with aggressive tumor biology and poor prognosis. Although targeted therapy has been tested for NRAS mutated melanoma, response rates still appear much weaker, than in BRAF mutated melanoma. While plenty of cell lines exist, however, only few melanogenic cell lines retain their in vivo characteristics. In this work we present an intensively pigmented and well-characterized cell line derived from a highly aggressive NRAS mutated cutaneous melanoma, named MUG-Mel2. We present the clinical course, unique morphology, angiogenic properties, growth characteristics using in vivo experiments and 3D cell culture, and results of the exome gene sequencing of an intensively pigmented melanogenic cell line MUG-Mel2, derived from a cutaneous metastasis of an aggressive NRAS p. Q61R mutated melanoma. Amongst several genetic alterations, mutations in GRIN2A, CREBP, PIK3C2G, ATM, and ATR were present. These mutations, known to reinforce DNA repair problems in melanoma, might serve as potential treatment targets. The aggressive and fast growing behavior in animal models and the obtained phenotype in 3D culture reveal a perfect model for research in the field of NRAS mutated melanoma.
PMID: 28522871 [PubMed - in process]
http://ift.tt/2rnUkpp
Anterior cingulate cortex supports effort allocation toward a qualitatively preferred option
Abstract
The anterior cingulate cortex (ACC) is known to be involved in effortful choice, yet its role in cost-benefit evaluation of qualitatively different rewards (more/less preferred), beyond magnitude differences (larger/smaller), is poorly understood. Selecting between qualitatively different options is a decision type commonly faced by humans. Here we assessed the role of ACC on a task that has primarily been used to probe striatal function in motivation. Rats were trained to stable performance on a progressive ratio schedule for sucrose pellets and were then given sham surgeries (control) or excitotoxic NMDA-lesions of ACC. Subsequently, a choice was introduced: chow was concurrently available while animals could work for the preferred sucrose pellets. ACC lesions produced a significant decrease in lever presses for sucrose pellets compared to control, whereas chow consumption was unaffected. Lesions had no effect on sucrose pellet preference when both options were freely available. When lab chow was not concurrently available, ACC lesioned rats exhibited similar lever pressing as controls. During a test under specific satiety for sucrose pellets, ACC lesioned rats also showed intact devaluation effects. The effects of ACC lesions in our task are not mediated by decreased appetite, a change in food preference, a failure to update value, or a learning deficit. Taken together, we found that ACC lesions decreased effort for a qualitatively-preferred option. These results are discussed with reference to effects of striatal manipulations and our recent report of a role for basolateral amygdala in effortful choice.
This article is protected by copyright. All rights reserved.
http://ift.tt/2q6sd9z
The truth is hidden in the details ‐ Comment on an observational study on transcatheter aortic valve implantation versus surgical aortic valve replacement in intermediate-risks patients
Adult cardiac surgeryAortic valve diseaseaortic valve replacementTranscatheter valve replacement
http://ift.tt/2rnJ38u
http://ift.tt/2rnJ38u
Corrigendum to ‘European risk models for morbidity (EuroLung1) and mortality (EuroLung2) to predict outcome following anatomic lung resections: an analysis from the European Society of Thoracic Surgeons database’ [Eur J Cardiothorac Surg 2017;51:490-497]†
The authors bring to the attention of the readers that there is an error in the coefficient of the intercept of the Eurolung2 logistic mortality model reported in Table 6 and on page 5 under the paragraph Analysis of Mortality. The correct intercept coefficient for the Eurolung2 logistic mortality model should read -5.82 instead of -5.029. As a consequence the logit of Eurolung2 is the following: -5.82 + 0.903Xsex male (coded 1 for male and 0 for female) + 0.044Xage + 0.264XCAD (coded 1 for presence of CAD) + 0.582XCVD (coded 1 for presence of CVD) -0.064XBMI + 0.300Xextended resection (coded 1 for extended resection) + 0.929X pneumonectomy (coded 1 for pneumonectomy and 0 for lesser resection) + 0.894Xthoracotomy (coded 1 for thoracotomy and 0 for VATS) - 0.009XppoFEV1.
http://ift.tt/2q38o3A
http://ift.tt/2q38o3A
Unplanned cardiac reoperations and interventions during long-term follow-up after the Norwood procedure†
Abstract
OBJECTIVES: Patients with hypoplastic left heart syndrome or related malformations are predominantly treated with a 3-stage palliation. Anatomic or physiologic problems can lead to unplanned additional surgical or catheter interventions during single ventricle palliation. Changes in operative technique may have an impact on the reoperation rate.METHODS: Between 1997 and 2014, 317 Norwood procedures were performed at our centre. A retrospective single centre investigation was carried out concerning incidence, timing, indication and type of unplanned interstage cardiac reoperations and catheter interventions during follow-up of Norwood patients. Patients were followed from birth until the end of 2015. Cardiac procedures taking place at the time of the bidirectional Glenn or Fontan procedure or heart transplantation were not included.RESULTS: Sixty-five of the Norwood patients (20.5%) had at least one additional surgical cardiac procedure. Nine patients (2.8%) needed open procedures prior to the Norwood operations, 11.0% had procedures in the interstage I, 3.5% in the interstage II and 9.1% of the Fontan patients had cardiac reoperations afterwards. Main indications for unplanned surgery were insufficient pulmonary perfusion and tricuspid regurgitation. Eighty-one patients (25.6%) had at least one interstage catheter intervention during follow-up mainly addressing stenosis of the pulmonary arteries, aortic arch stenosis or aortopulmonary collaterals.CONCLUSIONS: The number of unplanned reoperations and interventions during staged palliation is remarkably high showing surgical peaks in the interstage I and after the Fontan procedure and an interventional peak in the interstage II. Thorough early information of the parents about possibly anticipated additional procedures is necessary.http://ift.tt/2q3kn0Y
An alternative cardiopulmonary bypass strategy for intracaval baffle repair of scimitar syndrome
Abstract
Intracaval buffle repair of scimitar syndrome is classically performed under deep hypothermic circulatory arrest or using low-flow modalities of cardiopulmonary bypass with peripheral cannulation. We propose an alternative perfusion approach to the procedure using total intrapericardial cannulation under full-flow normothermic cardiopulmonary bypass.http://ift.tt/2rnVHV5
Fate of the dissected aortic arch after ascending replacement in type A aortic dissection †
Abstract
OBJECTIVES: To evaluate the fate of a dissected aortic arch after limited surgical repair of type A aortic dissection.METHODS: Of the 271 patients operated for acute type A dissection between 2001 and 2015, 86 (age 57 ± 13 years, 74% men) with predischarge computed tomographic (CT) scans had a residual dissection in the arch. Aortic diameters, lengths, ellipticity and communications between lumina were assessed using predischarge and follow-up CT scans. The median CT scan follow-up was 31 months (first quartile 15, third quartile 52).RESULTS: The largest increase in the total aortic diameter at follow-up was 20 mm distal to the left subclavian artery (median +4.0 mm; first quartile +1.5, third quartile +9.2 mm; P = 0.004), with an average growth rate of 1.5 mm/year (first quartile 0.6, third quartile 3.9 mm). The true lumen diameter was unchanged at follow-up. At least 1 communication between the true and the false lumina was observed in 80% of patients on the predischarge CT scan, and 70% had communications at the distal aorta–graft anastomosis. Accelerated increase in the diameter of the dissected aorta was associated with the number of communications between the lumina, communication at the distal anastomosis and false lumen perfusion (all, P < 0.001).CONCLUSIONS: Dissection of the residual aortic arch leads to aortic growth that may result in an aneurysm requiring treatment. The number of communications between the lumina, communication at the distal anastomosis and false lumen perfusion are associated with the accelerated aortic growth. Endovascular repair may be difficult due to the small true lumen and the presence of many communications between the lumina.http://ift.tt/2q32hwp
Thoracic surgeons in multiple/mass casualty scenario: are we ready?
Damage control thoracic surgeryChest traumaEducationMass casualty
http://ift.tt/2ro6tuz
http://ift.tt/2ro6tuz
Impact of sarcopenia on the outcomes of elective total arch replacement in the elderly †
Abstract
OBJECTIVES: The purpose of this study was to identify the cut-off value of sarcopenia based on the psoas muscle area index and evaluate early and late outcomes following elective total arch replacement in the elderly.METHODS: Sarcopenia was assessed by the psoas muscle area index [defined as the psoas muscle area at the L3 level on computed tomography (cm2)/body surface area (m2)]. The cut-off value for sarcopenia was defined as > 2 standard deviations below the mean psoas muscle area index value obtained from 464 normal control patients. Between October 1999 and July 2015, 266 patients who were ≥ 65 years and had undergone psoas muscle area index measurement underwent elective total arch replacement. These patients were classified into the sarcopenia (Group S, n = 81) and non-sarcopenia (Group N, n = 185) groups.RESULTS: The mean age was 76.2 ± 5.6 years in Group S and 75.7 ± 5.7 years in Group N (P = 0.553). Hospital mortality was 3.7% (3/81) in Group S and 2.2% (4/185) in Group N (P = 0.483). Mean follow-up was 48.3 ± 38.7 months. Five-year survival was significantly worse in Group S (S: 63.2 ± 6.6% vs N: 88.7 ± 2.6%, P < 0.001). A multivariable Cox proportional hazard analysis showed that sarcopenia significantly predicted poor survival (hazard ratio 2.59; 95% confidence interval 1.27–5.29; P = 0.011).CONCLUSIONS: Sarcopenia did not predict hospital death following total arch replacement, but it was negatively associated with overall survival. Sarcopenia can be an additional risk factor to estimate the outcomes of thoracic aortic surgery.http://ift.tt/2q3g9GL
Surgical management of penetrating thoracic injuries during the Paris attacks on 13 November 2015
Abstract
OBJECTIVES: The Paris terrorist attacks on 13 November 2015 caused 482 casualties, including 130 deaths and 352 wounded. Facing these multisite terrorist attacks, Parisian public and military hospitals simultaneously managed numerous patients with penetrating thoracic injuries. The aim of this study was to analyse this cohort, the injury patterns, and assess the results of this mobilization.METHODS: The clinical records of all patients admitted to Parisian public and military hospitals with a penetrating thoracic injury related to the Paris 13 November terrorist attacks were reviewed.RESULTS: The study group included 25 patients (7% of the casualties) with a mean age of 34 ± 8 years and a majority of gunshot wounds (n = 20, 80%). Most patients presented with severe thoracic injury (Abbreviated Injury Score Thorax 3.3 ± 1.2), and also associated non-thoracic injuries in 21 cases (84%). The mean Injury Severity Score was 26.8 ± 9.4. Eight patients (32%) were managed with chest tube insertion and 17 (68%) required thoracic surgery. Lung resection, diaphragmatic repair, and lung suture were performed in 6 (36%), 6 (35%), and 5 cases (29%), respectively. Extra-thoracic surgical procedures were performed in 16 patients, mostly for injuries to the extremities. Postoperative mortality was 12% (n = 3) and postoperative morbidity was 60% (n = 15),CONCLUSIONS: The coordination of Parisian military and civilian hospitals allowed the surgical management of 25 patients. The mortality is high but consistent with what has been reported in previous series. The current times expose us to the threat of new terrorist attacks and require that the medical community be prepared.http://ift.tt/2rod4oz
Common atrioventricular valve failure during single ventricle palliation†
Abstract
OBJECTIVES: To determine the risk of atrioventricular valve failure (valve intervention or moderate or greater regurgitation) during the lifetime of patients with single ventricle physiology and common atrioventricular valve.METHODS: Patients' data were extracted from an existing bi-national, population based registry. A retrospective review of their medical records was undertaken to determine the incidence of atrioventricular valve repair/replacement or moderate or greater regurgitation.RESULTS: From a registry of 1468 Fontan survivors, 136 patients with common atrioventricular valve were identified. Complete echocardiographic follow-up was available for 114 patients. Median length of follow-up was 10.2 years (interquartile range 5–15 years). Twenty-five year survival and freedom from Fontan failure were 94% [95% confidence interval (CI), 88–100%] and 74% (95% CI, 64–87%), respectively. Twenty-eight patients underwent 24 initial repairs and 4 replacements. The 24 patients undergoing repair subsequently needed 6 re-repairs, 2 replacements and 8 had moderate or greater regurgitation at last follow-up. Four-year freedom from atrioventricular valve repair failure was 50% (95% CI, 34–75%). An additional 30 patients developed moderate or greater atrioventricular valve regurgitation (6 New York Heart Association ≥3, 10 Fontan failures, 0 deaths). Cumulative incidence of the composite endpoint of atrioventricular valve failure at 28 years was 62% (95% CI, 49–74%).CONCLUSIONS: Patients with single ventricle physiology and common atrioventricular valve experience a continuous decline in valve function. The majority of patients experience valve failure in the first 30 years of life.http://ift.tt/2q3s6w9
The flaws in the detail of an observational study on transcatheter aortic valve implantation versus surgical aortic valve replacement in intermediate-risks patients
Abstract
The PARTNER group recently published a comparison between the latest generation SAPIEN 3 transcatheter aortic valve implantation (TAVI) system (Edwards Lifesciences, Irvine, CA, USA) and surgical aortic valve replacement (SAVR) in intermediate-risk patients, apparently demonstrating superiority of the TAVI and suggesting that TAVI might be the preferred treatment method in this risk class of patients. Nonetheless, assessment of the non-randomized methodology used in this comparison reveals challenges that should be addressed in order to elucidate the validity of the results. The study by Thourani and colleagues showed several major methodological concerns: suboptimal methods in propensity score analysis with evident misspecification of the propensity scores (PS; no adjustment for the most significantly different covariates: left ventricular ejection fraction, moderate–severe mitral regurgitation and associated procedures); use of PS quintiles rather than matching; inference on not-adjusted Kaplan–Meier curves, although the authors correctly claimed for the need of balancing score adjusting for confounding factors in order to have unbiased estimates of the treatment effect; evidence of poor fit; lack of data on valve-related death.These methodological flaws invalidate direct comparison between treatments and cannot support authors' conclusions that TAVI with SAPIEN 3 in intermediate-risk patients is superior to surgery and might be the preferred treatment alternative to surgery.http://ift.tt/2rolSem
Improved long-term outcomes in double-inlet left ventricle and tricuspid atresia with transposed great arteries: systemic outflow tract obstruction present at birth defines long-term outcome
Abstract
OBJECTIVES: In 2 subtypes of functional single ventricle, double inlet left ventricle (DILV) and tricuspid atresia with transposed great arteries (TA-TGA), systemic output passes through an outflow chamber before entering the aorta. Intracardiac obstruction to this pathway causing systemic outflow tract obstruction (SOTO) may be present at birth or develop over time. Long-term survival after Fontan has not been defined. We defined outcomes utilizing records from 2 centres that were cross-checked with data from a bi-national Fontan Registry for completeness and accuracy.METHODS: Two hundred and eleven patients were identified, 59 TA-TGA,152 DILV. Median follow-up was 17 years (range 4 days to 49.8 years). The Kaplan–Meier method was used for all of the time to event analyses and the log-rank test was used to compare the time-to-events. Cox proportional hazard models were used to test the association between potential predictors and time-to-event end-points. RESULTS: TA-TGA had reduced survival compared to DILV (cumulative risk of death 28.8% vs 11%, hazard ratio (HR) 3.1 (95% confidence interval (CI) 1.6–6.1), P = 0.001). In both groups, SOTO at birth carried a worse prognosis HR 3.54 (1.36–9.2, P = 0.01). SOTO was not more common in either morphology at birth (P = 0.20). Periprocedural mortality accounted for 40% of deaths. Fontan was achieved in 82%, DILV were more likely to achieve Fontan than TA-TGA (91% vs 60%, P <0.001). After Fontan there were 9 deaths (4%) with no difference according to morphology.CONCLUSIONS: Patients with TA-TGA have poorer outcomes than those with DILV, affecting survival and likelihood of achieving Fontan. SOTO at birth carries a high risk of mortality suggesting that, when present, initial surgical management should address this.http://ift.tt/2q3pJJM
Takayasu’s arteritis with total occlusion of the distal thoraco-abdominal aorta involving multiple visceral arteries
Takayasu's diseaseAortic occlusionVisceral ischaemia
http://ift.tt/2roq8dL
http://ift.tt/2roq8dL
Comparison of aortic arch repair using the endovascular technique, total arch replacement and staged surgery†
Abstract
OBJECTIVES: We evaluated the operative and long-term outcomes of various approaches for aortic arch repair.METHODS: A total of 436 consecutive patients who underwent aortic arch repair from January 2001 to March 2016 in our centre were evaluated. Of these, 276 underwent conventional total arch replacement (TAR), and 118 underwent thoracic endovascular repair (TEVAR). The remaining 42 patients underwent staged thoracic endovascular repair (STEVAR). A total of 72 patients in the TEVAR group were matched to 72 patients who underwent open surgery including TAR or STEVAR by using propensity score analysis.RESULTS: Surgical outcomes showed shorter ICU and hospital stay in the TEVAR group (P < 0.001 and P < 0.001, respectively). The 30-day mortality and neurologic dysfunction showed no significant difference among the three groups (2.8 and 5.4% in TAR group, 1.7 and 8.5% in TEVAR group and 0 and 2.4% in STEVAR group; P = 0.500 and P = 0.297, respectively). Long-term survival was not significantly different among the three groups (78% in TAR group, 67% in TEVAR group and 81% in STEVAR group at 5 years; P = 0.123). Freedom from aortic reintervention was lower in the TEVAR group than in other groups (98% in TAR, 92% in TEVAR and 97% in STEVAR at 5 years, P = 0.040).CONCLUSIONS: Operative outcomes showed no significant differences between the groups except for early recovery after TEVAR. Long-term survival was similar between groups; however, TEVAR had inferior reintervention free rate.http://ift.tt/2q3pJtg
Fatal bilateral haemopneumothoraces following double-lung transplantation caused by pretransplant colonization by Scedosporium apiospermum
Lung transplantation Haemothorax Pneumothorax Scedosporium Apiospermurm
http://ift.tt/2rod3kv
http://ift.tt/2rod3kv
The hemi-Mustard, bidirectional Glenn and Rastelli procedures for anatomical repair of congenitally corrected transposition of the great arteries/left ventricular outflow tract obstruction with positional heart anomalies†
Abstract
OBJECTIVES: The hemi-Mustard and bidirectional Glenn (BDG) procedures combined with the Rastelli procedure have been applied to selected cases of congenitally corrected transposition of the great arteries (ccTGA) for potential benefit over the classic atrial switch procedure. The aim of this study was to analyse our experience with the hemi-Mustard, BDG and Rastelli procedures as an anatomical correction for patients with ccTGA/left ventricular outflow tract obstruction (LVOTO) with positional heart anomalies.METHODS: In this retrospective study, 31 consecutive patients with corrected transposition underwent the hemi-Mustard/BDG procedures with the Rastelli operation between 2011 and 2015. The median age was 5.4 (range: 0.75–12) years. Positional anomalies were present in all patients. Eleven patients underwent BDG initially; they then had the second-stage hemi-Mustard and Rastelli procedures; 'one-stage repair' (hemi-Mustard/BDG and the Rastelli procedures) was performed in 20 cases.RESULTS: There were no in-hospital deaths, and 3 patients received a pacemaker. One patient had an atrial baffle obstruction that was observed in the early postoperative period; 7 patients had prolonged pleural effusions that developed more frequently in the one-stage repair group (7/20 vs 0/11, P = 0.033). During the mean follow-up of 3.3 years, 1 late death was noted, and no conduit replacements were required. Twenty-five (83.3%) patients are in New York Heart Association classes I and II at the latest follow-up.CONCLUSIONS: Hemi-Mustard, BDG and the Rastelli procedures are technically feasible for correction of ccTGA/left ventricular outflow tract obstruction (LVOTO) and cardiac malposition. Nevertheless, postoperative pleural effusion is the most prevalent complication in the one-stage repair. Two-stage repair may reduce the risk of pleural effusion-related complications.http://ift.tt/2q3AOdT
Can Perceval sutureless valve reduce the rate of patient-prosthesis mismatch? †
Abstract
OBJECTIVES: The aim of this study is to compare the theoretical incidence of patient-prosthesis mismatch (PPM) in patients undergoing a sutureless or a sutured aortic valve replacement using an exact statistical matching.METHODS: Between May 2012 and March 2016, 65 patients with severe symptomatic aortic stenosis underwent a sutureless aortic valve replacement with the Perceval bioprosthesis in 2 centres. Moreover, 177 aortic valve replacements with conventional sutured bioprosthesis were performed between August 2003 and September 2015. Perceval and sutured patients were 1:1 exactly matched for sex and body surface area (BSA), resulting in 62 couples (sutureless: BSA 1.77 ± 0.16 m2, female 62.9% vs sutured: BSA 1.77 ± 0.15 m2, female 62.9%).RESULTS: After matching, the indexed effective orifice area was 1.50 ± 0.18 cm2/m2 and 0.81 ± 0.19 cm2/m2 in the sutureless and the sutured group, respectively (P < 0.001). No PPM occurred in patients who received a Perceval bioprosthesis (n = 62). In the sutured group (n = 62), 38 patients (61.3%) developed a PPM, which was moderate in 41.9% (n = 26) and severe in 19.4% (n = 12) (P < 0.001).CONCLUSIONS: The indexed effective orifice area of the sutureless group was significantly larger than in the sutured one. The incidence of PPM with the conventional sutured biprosthesis was 61.3%, while it decreases to 0% in the sutureless group. No PPM was reported in the sutureless valve group. Therefore, the Perceval sutureless valve provides larger effective orifice areas compared to the sutured conventional bioprosthesis and could be considered as a good option to reduce the risk of a PPM.http://ift.tt/2rnVcdu
Lymphovascular invasion and extracapsular invasion are risk factors for distant recurrence after preoperative chemoradiotherapy and oesophagectomy in patients with oesophageal squamous cell carcinoma
Abstract
OBJECTIVES: Patients with oesophageal squamous cell carcinoma have a high risk of disease recurrence even after trimodality treatments, which include preoperative chemoradiotherapy and oesophagectomy. We aimed to identify the histological factors that are associated with loco-regional and distant recurrence.METHODS: A retrospective review of a prospectively established database identified patients who received preoperative chemoradiotherapy and oesophagectomy for squamous cell carcinoma. The impact of histological factors, including surgical resection margins, lymphovascular invasion (LVI), perineural invasion (PNI), extracapsular invasion (ECI) and tumour regression grade (TRG), on disease recurrence was analysed.RESULTS: A total of 116 patients treated between 2009 and 2015 were included. Sixty-one patients developed disease recurrence, including 25 loco-regional and 49 distant recurrences, with a median disease-free interval of 6 months. Positive histological surgical resection margins were significantly associated with loco-regional recurrence, whereas pre-treatment N stage, ypT stage, ypN stage, positive surgical resection margins, TRG, LVI, PNI, ECI and TRG were significant prognostic factors for distant recurrence. Upon multivariate analysis, cN stage [hazard ratio (HR): 4.049; 95% confidence interval (CI): 1.242–13.200, P = 0.020], LVI (HR: 3.658; 95% CI: 1.891–7.078, P < 0.001) and ECI (HR: 2.393; 95% CI: 1.202–4.763, P = 0.013) remained independent factors for distant recurrence. The 1- and 3-year freedom from distant recurrence rates were 71.8 and 65.6%, respectively, when both LVI and ECI factors were absent, compared to 17.6 and 14.1% when either or both were present (P < 0.001).CONCLUSIONS: Patients with lymphovascular invasion and extracapsular invasion are at a high risk of distant recurrence after preoperative chemoradiotherapy and oesophagectomy. Effective systemic therapy and intensive surveillance are necessary in this group of patients.http://ift.tt/2q35RGv
Video-assisted thoracic surgery lobectomy does not offer any functional recovery advantage in comparison to the open approach 3 months after the operation: a case matched analysis†
Abstract
OBJECTIVES: The objective of the present study was to compare functional loss [forced expiratory volume in one second to forced vital capacity ratio (FEV1), DLCO and VO2max reduction] after VATS versus open lobectomies.METHODS: We performed a prospective observational study on 195 patients who had a pulmonary lobectomy from June 2010 to November 2014 and who were able to complete a 3-months functional evaluation follow-up program. Since the VATS technique was our first choice for performing lobectomies from January 2012, we divided the patients into two groups: the OPEN group (112 patients) and the VATS group (83 patients). The open approach was intended as a muscle sparing/nerve sparing lateral thoracotomy. Fourteen baseline factors were used to construct a propensity score to match the VATS-group patients with their OPEN-group counterparts. These two matched groups were then compared in terms of reduction of FEV1, DLCO and VO2max (Mann–Whitney test).RESULTS: The propensity score analysis yielded 83 well-matched pairs of OPEN and VATS patients. In both groups, 3 months postoperatively, we found a reduction in FEV1, DLCO and VO2max values (OPEN patients: FEV1–10%, DLCO –11.9%, VO2max – 5.5%; VATS patients: FEV1–7.2%, DLCO-10.6%, VO2max-6.9%). The reductions in FEV1, DLCO and VO2max were similar to those in the two matched groups, with a Cohen effect size <0.2 for all the comparisons.CONCLUSIONS: In 3 months, both OPEN patients and VATS patients experienced a reduction in their preoperative functional parameters. VATS lobectomy does not offer any advantages in terms of FEV1, DLCO and exercise capacity recovery in comparison to the muscle-sparing thoracotomy approach.http://ift.tt/2ro7AKN
Extensive infective endocarditis of the aortic root and the aortic-mitral continuity: a mitral valve sparing approach†
Abstract
OBJECTIVES: Severe cases of infective endocarditis (IE) of the aortic valve can cause aortic root destruction and affect the surrounding structures, including the aortic-mitral continuity, the anterior mitral valve leaflet and the roof of the left atrium. Reconstruction after resection of all infected tissue remains challenging. We describe our surgical approach and the mid-term results.METHODS: Between January 2004 and December 2015, 35 patients underwent surgery for extensive IE of the aortic valve with destruction of the aortic root, the aortic-mitral continuity and the mitral valve. Mean age was 60.4 ± 13.7; 26/35 (74%) patients had prosthetic valve endocarditis. Four patients were in critical preoperative state. Median EuroSCORE II was 18.0% [interquartile range (IQR) 11.0–26.7].RESULTS: Aortic root replacement was performed in 32 (91%) patients. The remaining patients underwent aortic valve replacement. Reconstruction of the aortic-mitral continuity and the roof of the left atrium were performed using a folded pericardial patch. In 28 patients (80%), mitral valve repair was performed. Postoperative mechanical circulatory support, acute kidney failure and surgical re-exploration were seen in 5 (16%), 10 (31%) and 4 (13%) patients, respectively. Early survival rate was 77% (27 patients). During a median follow-up of 29.8 months (IQR 6.4–62.9), 7 (26%) patients required reintervention (3–42 months after surgery); 4 were due to mitral incompetence, early in our experience.CONCLUSIONS: Extensive IE of the aortic root with destruction of the surrounding tissues remains a complex disease with high morbidity and mortality rates. Our technique allows native mitral valve preservation but is technically challenging.http://ift.tt/2q3sYRB
Defining epileptogenic networks: Contribution of SEEG and signal analysis
Summary
Epileptogenic networks are defined by the brain regions involved in the production and propagation of epileptic activities. In this review we describe the historical, methodologic, and conceptual bases of this model in the analysis of electrophysiologic intracerebral recordings. In the context of epilepsy surgery, the determination of cerebral regions producing seizures (i.e., the "epileptogenic zone") is a crucial objective. In contrast with a traditional focal vision of focal drug-resistant epilepsies, the concept of epileptogenic networks has been progressively introduced as a model better able to describe the complexity of seizure dynamics and realistically describe the distribution of epileptogenic anomalies in the brain. The concept of epileptogenic networks is historically linked to the development of the stereoelectroencephalography (SEEG) method and subsequent introduction of means of quantifying the recorded signals. Seizures, and preictal and interictal discharges produce clear patterns on SEEG. These patterns can be analyzed utilizing signal analysis methods that quantify high-frequency oscillations or changes in functional connectivity. Dramatic changes in SEEG brain connectivity can be described during seizure genesis and propagation within cortical and subcortical regions, associated with the production of different patterns of seizure semiology. The interictal state is characterized by networks generating abnormal activities (interictal spikes) and also by modified functional properties. The introduction of novel approaches to large-scale modeling of these networks offers new methods in the goal of better predicting the effects of epilepsy surgery. The epileptogenic network concept is a key factor in identifying the anatomic distribution of the epileptogenic process, which is particularly important in the context of epilepsy surgery.
http://ift.tt/2q6ijV7
The role of Metabolic Reprogramming in γ-Herpesvirus-associated Oncogenesis
Abstract
The γ-herpesviruses, EBV and KSHV, are closely associated with a number of human cancers. While the signal transduction pathways exploited by γ-herpesviruses to promote cell growth, survival and transformation have been reported, recent studies have uncovered the impact of γ-herpesvirus infection on host cell metabolism. Here, we review the mechanisms utilised by γ-herpesviruses to induce metabolic reprogramming in host cells, focusing on their ability to modulate the activity of metabolic regulators and manipulate metabolic pathways. While γ-herpesviruses alter metabolic phenotypes as a means to support viral infection and long-term persistence, this modulation can inadvertently contribute to cancer development. Strategies that target deregulated metabolic phenotypes induced by γ-herpesviruses provide new opportunities for therapeutic intervention. This article is protected by copyright. All rights reserved.
http://ift.tt/2ro933x
CpG island methylator phenotype identifies high risk patients among microsatellite stable BRAF mutated colorectal cancers
Abstract
The prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer remains unsettled. We aimed to assess the prognostic value of this phenotype analyzing a total of 1126 tumor samples obtained from two Norwegian consecutive colorectal cancer series. CIMP status was determined by analyzing the 5-markers CAGNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 by quantitative methylation specific PCR (qMSP). The effect of CIMP on time to recurrence (TTR) and overall survival (OS) were determined by uni- and multivariate analyses. Subgroup analyses were conducted according to MSI and BRAF mutation status, disease stage, and also age at time of diagnosis (<60, 60-74, ≥75 years). Patients with CIMP positive tumors demonstrated significantly shorter TTR and worse OS compared to those with CIMP negative tumors (multivariate hazard ratio [95% CI] 1.86 [1.31-2.63] and 1.89 [1.34-2.65], respectively). In stratified analyses, CIMP tumors showed significantly worse outcome among patients with microsatellite stable (MSS, P < 0.001), and MSS BRAF mutated tumors (P < 0.001), a finding that persisted in patients with stage II, III or IV disease, and that remained significant in multivariate analysis (P < 0.01). Consistent results were found for all three age groups. To conclude, CIMP is significantly associated with inferior outcome for colorectal cancer patients, and can stratify the poor prognostic patients with MSS BRAF mutated tumors. This article is protected by copyright. All rights reserved.
http://ift.tt/2q2Mhuk
Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist
New England Journal of Medicine, Ahead of Print.
http://ift.tt/2pVvrRZ
Varicella-zoster virus seroprevalence in children and adolescents in the pre-varicella vaccine era, Germany
In 2004, universal childhood varicella vaccination was introduced in Germany. We aimed to determine the age-specific prevalence of anti-varicella zoster virus (VZV) IgG-antibodies among children in the pre-var...
http://ift.tt/2rCu3A5
Short-term fasting promotes insulin expression in rat hypothalamus
Abstract
In the hypothalamus, insulin takes on many roles involved in energy homeostasis. Therefore the aim of this study was to examine hypothalamic insulin expression during the initial phase of the metabolic response to fasting. Hypothalamic insulin content was assessed by both radioimmunoassay and western blot. The relative expression of insulin mRNA was examined by q PCR. Immunofluorescence and immunohistochemistry were used to determine the distribution of insulin immunopositivity in the hypothalamus. After six-hour fasting, both glucose and insulin levels were decreased in serum but not in the cerebrospinal fluid. Our study showed for the first time that, while the concentration of circulating glucose and insulin decreased, both insulin mRNA expression and insulin content in the hypothalamic parenchyma were increased after short-term fasting. Increased insulin immunopositivity was detected specifically in the neurons of the hypothalamic periventricular nucleus and in the ependymal cells of fasting animals. These novel findings point to the complexity of mechanisms regulating insulin expression in the CNS in general and in the hypothalamus in particular.
This article is protected by copyright. All rights reserved.
http://ift.tt/2pVM9AN
Obesity and Brain Positron Emission Tomography
Abstract
Obesity, an increasingly common problem in modern societies, results from energy intake chronically exceeding energy expenditure. This imbalance of energy can be triggered by the internal state of the caloric equation (homeostasis) and non-homeostatic factors, such as social, cultural, psychological, environmental factors or food itself. Nowadays, positron emission tomography (PET) radiopharmaceuticals have been examined to understand the cerebral control of food intake in humans. Using 15O–H2 PET, changes in regional cerebral blood flow (rCBF) coupled to neuronal activity were reported in states of fasting, satiation after feeding, and sensory stimulation. In addition, rCBF in obese subjects showed a greater increase in insula, the primary gustatory cortex. 18F–fluorodeoxyglucose PET showed higher metabolic activity in postcentral gyrus of the parietal cortex and lower in prefrontal cortex and anterior cingulate cortex in obese subjects. In addition, dopamine receptor (DR) PET demonstrated lower DR availability in obese subjects, which might lead to overeating to compensate. Brain PET has been utilized to reveal the connectivity between obesity and brain. This could improve understanding of obesity and help develop a new treatment for obesity.
http://ift.tt/2r2xDan
Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist
New England Journal of Medicine, Ahead of Print.
http://ift.tt/2pVvrRZ
Cross-Disciplinary Perceptions of Structured Interprofessional Rounds in Promoting Teamwork Within an Academic Tertiary Care Obstetric Unit
http://ift.tt/2rBWG0c
Chronic Amphetamine Users Do Not Need More Drugs During General Anesthesia
http://ift.tt/2qE2hWv
Magic Mirror, on the Wall—Which Is the Right Study Design of Them All?—Part I
http://ift.tt/2qDGNJk
An Observational Assessment of Anesthesia Capacity in Madagascar as a Prerequisite to the Development of a National Surgical Plan
http://ift.tt/2qDZDjs
Exercise Combined With Ultrasound Attenuates Neuropathic Pain in Rats Associated With Downregulation of IL-6 and TNF-α, but With Upregulation of IL-10
http://ift.tt/2rBW2zW
Red Cell Transfusion–Associated Hemolysis in Cardiac Surgery: An Observational Cohort Study
http://ift.tt/2qDRuf9
Haptoglobin Administration in Cardiovascular Surgery Patients: Its Association With the Risk of Postoperative Acute Kidney Injury
http://ift.tt/2rnWEMW
A Retrospective Study to Evaluate the Effect of Concentration of Hypertonic Saline on Efficacy and Safety of Epidural Adhesiolysis
http://ift.tt/2qDUqZ2
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
