Journal of Cosmetic Dermatology, EarlyView.
Πέμπτη 17 Μαΐου 2018
NonScarring Diffuse Hair Loss in Women: a Clinico‐Etiological Study from tertiary care center in North‐West India
Identification of tumor margins using diffuse reflectance spectroscopy with an extended‐wavelength spectrum in a porcine model
Skin Research and Technology, EarlyView.
Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke: From the American Association of Neurological Surgeons (AANS), American Society of Neuroradiology (ASNR), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Canadian Interventional Radiology Association (CIRA), Congress of Neurological Surgeons (CNS), European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (E
Mobile Stroke Unit Reduces Time to Image Acquisition and Reporting [INTERVENTIONAL]
SUMMARY:
Timely administration of thrombolytic therapy is critical to maximizing the likelihood of favorable outcomes in patients with acute ischemic stroke. Although emergency medical service activation overall improves the timeliness of acute stroke treatment, the time from emergency medical service dispatch to hospital arrival unavoidably decreases the timeliness of thrombolytic administration. Our mobile stroke unit, a new-generation ambulance with on-board CT scanning capability, reduces key imaging time metrics and facilitates in-the-field delivery of IV thrombolytic therapy.
Radiation-Induced Myelitis: Initial and Follow-Up MRI and Clinical Features in Patients at a Single Tertiary Care Institution during 20 Years [SPINE]
SUMMARY:
Myelitis is a rare complication of radiation exposure to the spinal cord and is often a diagnosis of exclusion. A retrospective review of clinical records and serial imaging was performed to identify subjects with documented myelitis and a history of prior radiation. Eleven patients fulfilled the inclusion criteria. All patients had longitudinally extensive cord involvement with homogeneous precontrast T1 hyperintense signal in the adjacent vertebrae, corresponding to the radiation field. T2 signal abnormalities involving the central two-thirds of the cord were seen in 6/11 patients (55%). The degree of cord expansion and contrast enhancement was variable but was seen in 6 (54%) and 5 (45%) patients, respectively. On follow-up, 2 patients developed cord atrophy, while complete resolution was noted in 1. Clinical improvement was noted in 5 patients, with symptom progression in 2 patients. Our results suggest that radiation myelitis is neither universally progressive nor permanent, and some radiographic and clinical improvement may occur.
Balanced Steady-State Free Precession Sequence (CISS/FIESTA/3D Driven Equilibrium Radiofrequency Reset Pulse) Increases the Diagnostic Yield for Spinal Drop Metastases in Children with Brain Tumors [SPINE]
BACKGROUND AND PURPOSE:
Identification of spinal drop metastases is important in the staging and management of pediatric patients with primary brain tumors. Our aim was to assess the diagnostic utility of the balanced steady-state free precession (bSSFP) sequence (CISS/FIESTA/3D driven equilibrium radiofrequency reset pulse) for the detection of spinal drop metastases in pediatric patients with primary intracranial tumors.
MATERIALS AND METHODS:This was a retrospective study of 44 pediatric patients with primary intracranial tumors undergoing MR imaging spine evaluation for drop metastases before radiation treatment. All patients underwent a whole-spine MRI with both bSSFP and postcontrast T1WI sequences. Two neuroradiologists independently reviewed only the bSSFP sequence, then 1 week later only the postcontrast T1WI sequence.
RESULTS:Patients ranged from 1 to 18 years of age (mean, 7.1 ± 4.2 years) with 27 males and 17 females. The number of lesions per patient ranged from 1 to 13 and from 2 to 11 mm in size. Lesions suspicious for drop metastases were seen in 8 patients on the postcontrast T1WI (18%) compared with 10 patients on the bSSFP sequence (23%). Twenty-two drop metastases seen on the bSSFP sequence were not visible on the postcontrast T1WI, including nonenhancing drop metastases and multiple nodules of <3 mm. Interrater agreement was excellent for the bSSFP sequence (0.91) and the postcontrast T1 sequence (0.90).
CONCLUSIONS:The bSSFP sequence increased the diagnostic yield for the detection of drop metastases in pediatric patients with primary intracranial tumors and was particularly advantageous for small drop metastases (<3 mm) and nonenhancing metastases, and it decreased the number of false-positives. The bSSFP sequence may be an important adjunct to postcontrast T1WI for the evaluation of drop metastases.
Postnatal Brain Growth Assessed by Sequential Cranial Ultrasonography in Infants Born <30 Weeks' Gestational Age [PEDIATRICS]
BACKGROUND AND PURPOSE:
Brain growth in the early postnatal period following preterm birth has not been well described. This study of infants born at <30 weeks' gestational age and without major brain injury aimed to accomplish the following: 1) assess the reproducibility of linear measures made from cranial ultrasonography, 2) evaluate brain growth using sequential cranial ultrasonography linear measures from birth to term-equivalent age, and 3) explore perinatal predictors of postnatal brain growth.
MATERIALS AND METHODS:Participants comprised 144 infants born at <30 weeks' gestational age at a single center between January 2011 and December 2013. Infants with major brain injury seen on cranial ultrasonography or congenital or chromosomal abnormalities were excluded. Brain tissue and fluid spaces were measured from cranial ultrasonography performed as part of routine clinical care. Brain growth was assessed in 3 time intervals: <7, 7–27, and >27 days' postnatal age. Data were analyzed using intraclass correlation coefficients and mixed-effects regression.
RESULTS:A total of 429 scans were assessed for 144 infants. Several linear measures showed excellent reproducibility. All measures of brain tissue increased with postnatal age, except for the biparietal diameter, which decreased within the first postnatal week and increased thereafter. Gestational age of ≥28 weeks at birth was associated with slower growth of the biparietal diameter and ventricular width compared with gestational age of <28 weeks. Postnatal corticosteroid administration was associated with slower growth of the corpus callosum length, transcerebellar diameter, and vermis height. Sepsis and necrotizing enterocolitis were associated with slower growth of the transcerebellar diameter.
CONCLUSIONS:Postnatal brain growth in infants born at <30 weeks' gestational age can be evaluated using sequential linear measures made from routine cranial ultrasonography and is associated with perinatal predictors of long-term development.
Neuroimaging Findings of Zika Virus-Associated Neurologic Complications in Adults [REVIEW ARTICLE]
SUMMARY:
When the first suspected cases of neurologic disorders associated with the Zika virus were noticed in Brazil in late 2015, several studies had been conducted to understand the pathophysiology of the disease and its associated complications. In addition to its well-established association with microcephaly in neonates, the Zika virus infection has also been suggested to trigger other severe neurologic complications in adults, such as Guillain-Barré syndrome, radiculomyelitis, and meningoencephalitis. Hence, the Zika virus should be deemed a global threat that can cause devastating neurologic complications among individuals in all age ranges. The aim of this review was to further describe neuroimaging findings of Zika virus infection and associated neurologic complications found in adults.
Prediction of Borderzone Infarction by CTA in Patients Undergoing Carotid Embolization for Carotid Blowout [EXTRACRANIAL VASCULAR]
BACKGROUND AND PURPOSE:
Permanent common carotid artery and/or ICA occlusion is an effective treatment for carotid blowout syndrome. Besides postoperative thromboembolic infarction, permanent common carotid artery and/or ICA occlusion may cause borderzone infarction when the collateral flow to the deprived brain territory is inadequate. In this study, we aimed to test the predictive value of CTA for post–permanent common carotid artery and/or ICA occlusion borderzone infarction in patients with carotid blowout syndrome.
MATERIALS AND METHODS:In this retrospective study, we included 31 patients undergoing unilateral permanent common carotid artery and/or ICA occlusion for carotid blowout syndrome between May 2009 and December 2016. The vascular diameter of the circle of Willis was evaluated using preprocedural CTA, and the risk of borderzone infarction was graded as very high risk, high risk, intermediate risk, low risk, and very low risk.
RESULTS:The performance of readers' consensus on CTA for predicting borderzone infarction was excellent, with an area under receiver operating characteristic curve of 0.938 (95% confidence interval, 0.85–1.00). We defined very high risk, high risk, and intermediate risk as positive for borderzone infarction, the sensitivity, specificity, positive predictive value, and negative predictive value of CTA for borderzone infarction were 100% (7/7), 62.5% (15/24), 43.8% (7/16), and 100% (15/15), respectively. The interobserver reliability was excellent ( = 0.807). No significant difference in the receiver operating characteristic curves was found between the 2 readers (P = .114).
CONCLUSIONS:CTA can be used to predict borderzone infarction after permanent common carotid artery and/or ICA occlusion by measuring the collateral vessels of the circle of Willis.
European cancer mortality predictions for the year 2018 with focus on colorectal cancer
Abstract
Background
We projected cancer mortality statistics for 2018 for the European Union (EU) and its six more populous countries, using the most recent available data. We focused on colorectal cancer. Materials and methods
We obtained cancer death certification data from stomach, colorectum, pancreas, lung, breast, uterus, ovary, prostate, bladder, leukaemia, and total cancers from the World Health Organisation database and projected population data from Eurostat. We derived figures for France, Germany, Italy, Poland, Spain, the UK, and the EU in 1970–2012. We predicted death numbers by age group and age-standardized (world population) rates for 2018 through joinpoint regression models. Results
EU total cancer mortality rates are predicted to decline by 10.3% in men between 2012 and 2018, reaching a predicted rate of 128.9/100 000, and by 5.0% in women with a rate of 83.6. The predicted total number of cancer deaths is 1 382 000 when compared with 1 333 362 in 2012 (+3.6%). We confirmed a further fall in male lung cancer, but an unfavourable trend in females, with a rate of 14.7/100 000 for 2018 (13.9 in 2012, +5.8%) and 94 500 expected deaths, higher than the rate of 13.7 and 92 700 deaths from breast cancer. Colorectal cancer predicted rates are 15.8/100 000 men (−6.7%) and 9.2 in women (−7.5%); declines are expected in all age groups. Pancreatic cancer is stable in men, but in women it rose +2.8% since 2012. Ovarian, uterine and bladder cancer rates are predicted to decline further. In 2018 alone, about 392 300 cancer deaths were avoided compared with peak rates in the late 1980s. Conclusion
We predicted continuing falls in mortality rates from major cancer sites in the EU and its major countries to 2018. Exceptions are pancreatic cancer and lung cancer in women. Improved treatment and—above age 50 years—organized screening may account for recent favourable colorectal cancer trends.Taking it in the chin: vitamin K1 for the prevention of acneiform rash
In this issue of Annals of Oncology, Hofheinz et al. study the efficacy of a topical formulation of vitamin K1 in the prevention of a disfiguring toxicity resulting from epidermal growth factor receptor (EGFR) inhibitors [1]. An acneiform rash on the face and upper body develops in the majority of patients treated with EGFR inhibitors [2]. In addition to its psychosocial impact [3], it is associated with symptoms of pruritus and pain, may result in secondary infections [4], all of which may lead to inconsistencies in the dosing of causal anticancer agents [5]. Since the rash has been correlated with antitumor efficacy across most solid tumors in which it has been employed [6], mitigating this untoward event has been the subject of research for the past 15 years.
Targeting cell cycle dependencies represent a novel therapeutic approach for selected sarcoma subgroups
Adult soft tissue sarcoma (STS) represents a group of rare malignant tumours associated with a very poor prognosis in the metastatic setting, with <20% of patients surviving 5 years after diagnosis [1]. Beyond their biological aggressiveness, under-recognition misdiagnosis of STS also contributes to this increased mortality. Management by specialized multidisciplinary boards is recommended and improves patients' survival [2].
ESR1 and endocrine therapy resistance: more than just mutations
Estrogen receptor (ER)-positive breast cancer accounts for 70%–80% of all diagnosed breast cancers [1]. The adoption of endocrine therapies, including ER modulators/degraders (SERMs/SERDs), which antagonize ER, and aromatase inhibitors (AIs), which suppress estrogen synthesis, as the mainstay of treatment of ER-positive breast cancer patients has resulted in substantial survival benefit for patients with early stage disease [2]. Treating ER-positive metastatic breast cancer (MBC), however, remains a significant clinical challenge, due to the development of secondary resistance to all modalities of endocrine therapy [3]. Recently, studies have identified recurrent somatic mutations within the ligand-binding domain (LBD) of ESR1 (encoding ER) in >30% of ER-positive MBC [4–8]. These mutations alter the conformation of ER and produce a constitutively active form of the protein. Mutations at residues 536–538, in particular, promote ER activity in the absence of ligand, resulting in resistance to AIs and reduced sensitivity to SERMs/SERDs [4, 5]. ESR1 fusion genes have also been reported in ER-positive MBCs; however, a detailed description of their manifestations and clinical prevalence is lacking [9]. In this issue of Annals of Oncology, Hartmaier et al. reported the identification of recurrent hyperactive ESR1 fusion genes in breast cancers resistant to endocrine therapy [10], adding to the diversity of reported ESR1 alterations.
Time is up for PD-L1 testing standardization in lung cancer
The treatment options for patients with advanced non-small-cell lung carcinoma have undergone major changes in the recent years, particularly after the FDA approval of PD-1/PD-L1 immune checkpoint inhibitors nivolumab, pembrolizumab and atezolizumab) [1–8]. Each PD-1/PD-L1 inhibitor was approved together with a specific PD-L1 immunohistochemistry assay used in the clinical trials. In addition to unique primary antibody, each assay is optimized for use with a different detection system (i.e. Dako Link 48 and Ventana BenchMark) and a different diagnostic kit. Furthermore, the unique scoring algorithms for immunohistochemical assays were co-developed with each immune checkpoint inhibitor based on predictive values shown in the clinical trials. The one drug–one assay approach is challenging to implement in clinical practice as most laboratories do not use all of the staining platforms and such practice leads to avoidable escalation of laboratory testing cost and health care in general. The main question is whether laboratories will make effort to implement the FDA approved predictive assays for one or more anti-PD-1/PD-L1 checkpoint inhibitors or implement one or more affordable laboratory developed tests (LDTs) using already available testing platforms. To find the answer to this question it is essential to determine analytical concordance between commercially available PD-L1 immunohistochemical assays. Several studies showed an excellent analytical concordance between either FDA approved or LDTs [9–13]. Three assays SP263, 22C3 and 28-8 showed a high concordance in percentage of PD-L1 membrane staining of tumor cells at any intensity. In contrast, lower expression of PD-L1 on tumor cells was observed with SP142 clone. In terms of interpretation, interobserver concordance was high for tumor cell PD-L1 expression, while it was low for immune cells.
Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer
Abstract
Background
There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methods
In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m2 intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS). Results
A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%). Conclusions
Vinflunine 280 mg/m2 q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m2 merits evaluation. ClinicalTrials.gov
NCT01091168.Computational prediction of neoantigens: do we need more data or new approaches?
The capability of the immune system for self-recognition has recently become the focus of interest for a broadening research community due to the impressive clinical results achieved with immune checkpoint inhibitors and other immunotherapies in the treatment of advanced metastatic carcinoma [1]. A significant portion of this clinical efficacy is attributed to the fact that the genomic instability of cancer generates mutation-derived peptides (neopeptides) that are not present in normal cells. A subset of these neopeptides may be neoantigens (also called neoepitopes) which are recognized as alien by cytotoxic T cells. Ideally, a cell producing neoantigens should be eliminated by the immune system. However, tumors are able to inhibit this immune response by activating various checkpoint mechanisms; these can be overcome by the now widely used therapeutic agents of checkpoint inhibitors such as anti PD-L1 or anti-CTLA-4 antibodies. There is increasing evidence that such neoantigen-driven immune responses are responsible for the significant clinical response shown to immune checkpoint inhibitors in at least one specific type of tumors, microsatellite instable cancer [2, 3].
Predictive biomarkers and EGFR inhibitors in squamous cell carcinoma of head and neck (SCCHN)
Squamous cell carcinoma of the head and neck (SCCHN) represents the sixth most common cancer globally and accounts for ∼5% of all cancers [1, 2]. The management of these cancers is complex and requires a multidisciplinary approach with multi-modality treatments but the survival outcome of these patients remain poor [2].
Toward optimizing outcomes in Her2-positive gastric cancer: timing and genomic context matter
In 2010, the ToGA trial demonstrated a 2.7-month improvement in overall survival (OS) with the addition of the anti-HER2 monoclonal antibody trastuzumab to platinum-5-FU in first-line treatment of advanced HER2-positive gastric cancer [1]. Subsequent attempts to address HER2-directed therapies in first and second lines have been met with largely disappointing results [2–5]. In the phase III LOGiC trial, the addition of the small molecule HER2-inhibitor lapatinib to first-line CapeOx failed to improve OS in the primary efficacy population (12.2 versus 10.5, Hazard Ratio (HR) 0.91, P = 0.35), though preplanned subset analysis suggested a benefit with the addition of lapatinib in Asian patients (HR 0.68) and patients < 60 years old (HR 0.69) [2]. There was no correlation between Immunohistochemistry (IHC)-status and OS benefit in the study population, which were all amplified by FISH. Contemporary with the LOGiC trial was several publications associating magnitude of HER2 amplification with degree of benefit from trastuzumab, as well as the recognition that HER2-positive gastric cancer is a highly heterogeneous disease complicated by chronologic HER2 changes, and inter- and intratumoral variations in molecular features [6–9]. The incorporation of cell-free DNA (cfDNA) has allowed for perhaps more representative sampling of global tumor makeup, potentially facilitating identification of patient subsets with better or worse outcomes though limited prospective data exist in esophagogastric cancers [10].
Introducing whole-genome sequencing into routine cancer care: the Genomics England 100 000 Genomes Project
Large-scale sequencing studies such as the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) have begun to catalogue the spectra of somatic mutations present in different solid tumour types [1, 2]. However, to date there has been minimal traction for solid tumours in alignment of large-scale sequencing data to longitudinal data on therapy and outcome. Such data are essential if we are to better target conventional cytotoxics, as well as emerging drugs such as immunotherapeutics. Stratification using molecular markers could improve benefit against cost and side-effects, especially critical in the adjuvant setting. Molecular heterogeneity of tumours and confounding patient factors mean datasets of daunting size and depth will be required. Arguably these will only be achieved through molecular analyses as standard for cancer patients entering clinical trials and, by adopting a population level approach to molecular analysis of patients undergoing routine cancer treatments.
Overexpression of BLM promotes DNA damage and increased sensitivity to platinum salts in triple-negative breast and serous ovarian cancers
Abstract
Background
Platinum-based therapy is an effective treatment for a subset of triple-negative breast cancer and ovarian cancer patients. In order to increase response rate and decrease unnecessary use, robust biomarkers that predict response to therapy are needed. Patients and methods
We performed an integrated genomic approach combining differential analysis of gene expression and DNA copy number in sensitive compared with resistant triple-negative breast cancers in two independent neoadjuvant cisplatin-treated cohorts. Functional relevance of significant hits was investigated in vitro by overexpression, knockdown and targeted inhibitor treatment. Results
We identified two genes, the Bloom helicase (BLM) and Fanconi anemia complementation group I (FANCI), that have both increased DNA copy number and gene expression in the platinum-sensitive cases. Increased level of expression of these two genes was also associated with platinum but not with taxane response in ovarian cancer. As a functional validation, we found that overexpression of BLM promotes DNA damage and induces sensitivity to cisplatin but has no effect on paclitaxel sensitivity. Conclusions
A biomarker based on the expression levels of the BLM and FANCI genes is a potential predictor of platinum sensitivity in triple-negative breast cancer and ovarian cancer.Beyond second-line therapy in patients with metastatic colorectal cancer: a systematic review
Abstract
Background
The optimal chemotherapeutic regimen for use beyond the second line for patients with metastatic colorectal cancer (mCRC) remains unclear. Materials and methods
We systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the efficacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC. Studies were assessed for design and quality, and a qualitative data synthesis was conducted to understand the impact of treatment on overall survival and other relevant cancer-related outcomes. Results
The search yielded 938 references of which 68 were included for qualitative synthesis. There was limited evidence to support rechallenge with chemotherapy, targeted therapy or both. Compared with placebo, an overall survival benefit for trifluridine/tipiracil (also known as TAS-102) or regorafenib has been shown for patients previously treated with conventional chemotherapy and targeted therapy. There was no evidence to suggest a difference in efficacy between these treatments. Patient choice and quality of life at this stage of treatment should also be considered when choosing an appropriate therapy. Conclusions
These findings support the introduction of an approved agent such as trifluridine/tipiracil or regorafenib beyond the second line before any rechallenge in patients with mCRC who have failed second-line treatment.Lifestyle factors and risk of sporadic colorectal cancer by microsatellite instability status: a systematic review and meta-analyses
Abstract
Introduction
The association of lifestyle factors with molecular pathological subtypes of colorectal cancer (CRC), such as microsatellite instability (MSI), could provide further knowledge about the colorectal carcinogenic process. The aim of this review was to evaluate possible associations between lifestyle factors and risk of sporadic CRC by MSI status. Methods
PubMed and Web of Science were searched for studies investigating the association between alcohol, body mass index, dietary fiber, hormone replacement therapy (HRT), non-steroidal anti-inflammatory drugs, physical activity, red meat, smoking, or statin use, with MSI-high (MSI-H) and microsatellite stable (MSS) CRC. Meta-analyses were carried out to calculate summary relative risks (sRR). Results
Overall, 31 studies reporting on the association between lifestyle factors and CRC according to MSI status were included in this review. Ever smoking was associated with MSI-H (sRR = 1.62; 95% CI: 1.40–1.88) and MSS/MSI-low CRC (sRR = 1.10; 95% CI: 1.01–1.20), but the association was significantly stronger for MSI-H CRC. The use of HRT was associated with a 20% decrease (sRR = 0.80; 95% CI: 0.73–0.89) in the risk of MSS CRC, but was not associated with MSI-H CRC. An increase in body mass index per 5 kg/m2 was equally associated with MSS and MSI-H CRC (sRR = 1.22, in both cases), but was statistically significant for MSS CRC only (95% CI: 1.11–1.34 and 0.94–1.58, respectively). Limited evidence for associations between other lifestyle factors and CRC by MSI status exists. Conclusions
Lifestyle factors, such as HRT and smoking are differentially associated with the risk of MSI-H and MSS CRC. Further research on associations of lifestyle factors and CRC subtypes is necessary to provide a better understanding of the CRC disease pathway.Management of metastatic retroperitoneal sarcoma: a consensus approach from the Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG)†
Abstract
Introduction
Retroperitoneal sarcoma (RPS) is a rare disease accounting for 0.1%–0.2% of all malignancies. Management of RPS is complex and requires multidisciplinary, tailored treatment strategies at all stages, but especially in the context of metastatic or multifocal recurrent disease. Due to the rarity and heterogeneity of this family of diseases, the literature to guide management is limited. Methods
The Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaboration of sarcoma experts from all disciplines convened in an effort to overcome these limitations. The TARPSWG has compiled the available evidence surrounding metastatic and multifocally recurrent RPS along with expert opinion in an iterative process to generate a consensus document regarding the complex management of this disease. The objective of this document is to guide sarcoma specialists from all disciplines in the diagnosis and treatment of multifocal recurrent or metastatic RPS. Results
All aspects of patient assessment, diagnostic processes, local and systemic treatments, and palliation are reviewed in this document, and consensus recommendations provided accordingly. Recommendations were guided by available evidence, in conjunction with expert opinion where evidence was lacking. Conclusions
This consensus document combines the available literature regarding the management of multifocally recurrent or metastastic RPS with the practical expertise of high-volume sarcoma centers from multiple countries. It is designed as a tool for decision making in the complex multidisciplinary management of this condition and is expected to standardize management across centers, thereby ensuring that patients receive the highest quality care.Epigenetic modifiers as new immunomodulatory therapies in solid tumours
Abstract
Background
Immune therapies have revolutionized cancer treatment over the last few years by allowing improvements in overall survival. However, the majority of patients is still primary or secondary resistant to such therapies, and enhancing sensitivity to immune therapies is therefore crucial to improve patient outcome. Several recent lines of evidence suggest that epigenetic modifiers have intrinsic immunomodulatory properties, which could be of therapeutic interest. Material and methods
We reviewed preclinical evidence and clinical studies which describe or exploit immunomodulatory properties of epigenetic agents. Experimental approaches, clinical applicability and corresponding ongoing clinical trials are described. Results
Several epigenetic modifiers, such as histone deacetylase inhibitors, DNA methyl transferase inhibitors, bromodomain inhibitors, lysine-specific histone demethylase 1 inhibitors and enhancer of zeste homolog 2 inhibitors, display intrinsic immunomodulatory properties. The latter can be achieved through the action of these drugs either on cancer cells (e.g. presentation and generation of neoantigens, induction of immunogenic cell death, modulation of cytokine secretion), on immune cells (e.g. linage, differentiation, activation status and antitumor capability), or on components of the microenvironment (e.g. regulatory T cells and macrophages). Several promising combinations, notably with immune checkpoint blockers or adoptive T-cell therapy, can be envisioned. Dedicated clinically relevant approaches for patient selection and trial design will be required to optimally develop such combinations. Conclusion
In an era where immune therapies are becoming a treatment backbone in many tumour types, epigenetic modifiers could play a crucial role in modulating tumours' immunogenicity and sensitivity to immune agents. Optimal trial design, including window of opportunity trials, will be key in the success of this approach, and clinical evaluation is ongoing.Genetic profiling of cell-free DNA from cerebrospinal fluid: opening the barrier to leptomeningeal metastasis in EGFR-mutant NSCLC
Over the past decade, remarkable progress has been made in the management of advanced non-small-cell lung cancer (NSCLC), when tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors have been added to the therapeutic armamentarium. Indeed, dramatic responses to epidermal growth factor receptor (EGFR)-TKIs are observed in patients with NSCLC harbouring activating EGFR driver mutations [1, 2]. Unfortunately, all tumours ultimately develop secondary resistance, half of these due to the acquirement of the gatekeeper EGFR T790M mutation [3]. Fortunately, T790M-induced resistance can now be successfully addressed by use of third-generation EGFR-TKIs that show impressive activity in these patients [4].
Statistical controversies in clinical research: limitations of open-label studies assessing antiangiogenic therapies with regard to evaluation of vascular adverse drug events—a meta-analysis
Abstract
Background
Previous meta-analyses have shown paradoxical increased risk of bleeding and thrombotic events in patients receiving antiangiogenics (AA) that may be simply explained by the studies design included. By a meta-epidemiological approach, we aim to investigate the impact of double-blind (DB) and open-label study designs on the risks of bleeding, venous thrombotic events (VTE) and arterial thrombotic events (ATE) in cancer patients treated with AA. Materials and methods
We searched Medline, Cochrane, ClinicalTrials.gov databases and proceedings of major oncology congresses for clinical trials published from January 2003 to January 2016. Randomized clinical trials that assigned patients with solid cancers to AA or control groups were eligible for inclusion. Combined odds ratios (ORs) for the risks of bleeding events, VTE and ATE were calculated for open and DB trials. Estimation bias of the treatment effect was determined by the ratio of OR, by dividing the OR values obtained in open-label trials by those obtained in DB trials. Results
The literature-based meta-analysis included 166 trials (72 024 patients). For bleeding events, comparison of AA versus control yielded an overall OR of 2.41 [95% confidence interval (95% CI) 2.12–2.73; P < 0.001], but this risk was overestimated by 1.68 (95% CI 1.33–2.13) in open-label studies. Concerning VTE, the OR was 1.19 (95% CI 1.04–1.35; P = 0.012) overall with AA, but this effect disappears when considering only DB trials (OR 0.99, 95% CI 0.83–1.17). The corresponding ratio of OR showed a significant overestimation of 1.53 (95% CI 1.19–1.96) in open-label trials. For ATE, an OR of 1.59 (95% CI 1.30–1.94; P < 0.001) was observed, associated with a significant overestimation of 1.65 (95% CI 1.13–2.43) in open-label trials. Conclusions
Open-label studies overestimated the risk of vascular adverse events with AA by at least 50%. Meta-analyses assessing adverse drug events should therefore be restricted to DB randomized trials.Expression III: patients’ expectations and preferences regarding physician–patient relationship and clinical management—results of the international NOGGO/ENGOT-ov4-GCIG study in 1830 ovarian cancer patients from European countries
Abstract
Backround
The primary aim of this study was to investigate information needs and treatment preferences of patients with ovarian cancer, focusing especially on physician–patient relationship and treatment. Patients and methods
A questionnaire was developed based on the experiences of the national German survey 'Expression II', and was provided to patients with ovarian cancer either at initial diagnosis or with recurrent disease via Internet (online-version) or as print-out-version. Results
From December 2009 to October 2012, a total of 1830 patients with ovarian cancer from eight European countries (Austria, Belgium, France, Germany, Italy, Poland, Romania, Spain) participated, 902 (49.3%) after initial diagnosis and 731 (39.9%) with recurrent ovarian cancer. The median age was 58 years (range 17–89). Nearly all patients (96.2%) had experienced upfront surgery followed by first-line chemotherapy (91.8%). The majority of patients were satisfied with the completeness and comprehensibility of the explanation about the diagnosis and treatment options. The three most important aspects, identified by patients to improve the treatment for ovarian cancer included: 'the therapy should not induce alopecia' (42%), 'there must be more done to counter fatigue' (34.5%) and 'the therapy should be more effective' (29.7%). Out of 659 (36%) patients, who were offered participation in a clinical trial, 476 (26%) were included. Conclusion
This study underlines the high need of patients with ovarian cancer for all details concerning treatment options irrespective of their cultural background, the stage of disease and the patient's age. Increased information requirements regarding potential side effects and treatment alternatives were recorded. Besides the need for more effective therapy, alopecia and fatigue are the most important side effects of concern to patients.Developing androgen receptor targeting for salivary gland cancers
Salivary gland cancers (SGCs) are rare malignancies that can arise from major (parotid, submandibular, sublingual) or minor glands present throughout the upper aerodigestive tract. These tumors encompass a diverse set of diseases representing more than 20 different histologic subtypes with distinct clinical behaviors, genomic/molecular profiles, and responsiveness to drug therapy [1–3]. Similar to other rare diseases, the lack of prospective drug trials focused on singular SGC tumor types makes evidence-based management a challenge.
Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases
Abstract
Background
Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC. Patients and methods
Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses. Results
After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50–0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61–0.81). Rates of treatment-related hepatic adverse events (primarily grade 1–2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%). Conclusions
After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated. Clinical trial registration
CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.Functional and Anatomical Outcomes of Facial Nerve Injury With Application of Polyethylene Glycol
This experiment assesses whether the application of polyethylene glycol in addition to neurorrhaphy can improve functional outcomes and synkinesis in a rat model of facial nerve injury.
Zygomaticomaxillary Complex–Orbit Fracture Alignment—Buccal vs Orbital Approach Techniques
This study proposes the use of a sublabial incision without a lower eyelid incision to address zygomaticomaxillary complex fractures involving the orbital rim.
Asian Upper Blepharoplasty
This Surgical Pearl describes the eyelid crease blepharoplasty, or aesthetic blepharoplasty, in Asian patients using a beveled approach and trapezoidal debulking of preaponeurotic tissues.
Supraclavicular Artery Island Flap in Patients With Ports or Pacemakers
This case report examines the technique and safety of supraclavicular artery island flap harvest in patients with subclavian devices such as pacemakers and ports.
Surgical Procedure Grid for Increased Safety and Communication
This Viewpoint describes the Surgical Procedure Grid, a tool to help organization in the operating room during multisite surgery.
Adverse Events in Facial Implant Surgery and Associated Litigation
This cross-sectional study examines complications and litigation following facial implant surgery.
Complications and Reoperations in Mandible Angle Fractures
This cohort study compares the use of transcervical and transoral techniques to repair mandible fractures in patients.
JAMA Facial Plastic Surgery—The Year in Review, 2017
JAMA Facial Plastic Surgery is nearly 20 years old—youthful compared with many of the JAMA Network journals! The biggest news for the journal this year was the impressive jump in our impact factor to 2.7, which positions the journal in the top echelon among journals that publish similar content. As we have attracted higher-quality scientific submissions, our acceptance rate for research manuscripts has now dipped to 24% (last year the rate was 33%) (Table). We will be carefully monitoring this trend because we wish to be inclusive and inviting to our research community while striving to be selective in showcasing the very best work of our colleagues.
Vermilionectomy in Malignant and Premalignant Lower Lip Lesions
This cohort study examines the effectiveness of vermilionectomy in patients with lower lip actinic cheilitis.
Anesthesia Duration and Head and Neck Microvascular Reconstruction Complications
This study examines the association of anesthesia duration with complications after microvascular reconstruction of the head and neck.
A Closer Look at the Analgesic Regimen After Rhinoplasty—Reply
In Reply We thank Kendall and Castro-Alves for taking the time to read and critically analyze our article. Their commentary was very insightful and thought provoking. First, to directly answer their inquiries, we did not use a consistent standardized intraoperative or perioperative pain regimen, although that would have been desirable. In large medical center and academic medical center hospitals, and especially now with large anesthesia groups, the ability to have the same anesthesia team even throughout a single case is difficult because different anesthesiologists and certified registered nurse anesthetists continually come in and out of the operating room to spell one another for breaks and leave at shift changes so that the person who started the anesthesia portion is often not the same as who ends the case and extubates the patient. We agree that pain management should be discussed and coordinated with the anesthesiology team, and this should be a proactive venture that is highly dependent on the ability of local anesthesia to quell the need for intravenous medications during the case.
Outcomes of Buccinator Treatment With Botulinum Toxin in Facial Synkinesis
This cohort study evaluates outcomes for patients treated with botulinum toxin applied to the buccinator muscle in the setting of facial synkinesis.
Current Trends in Management of Submental Liposis
This pooled analysis of phase 3 trials evaluates the efficacy of deoxycholic acid injection compared with submental liposuction among patients with submental liposis.
Adverse Events and Litigation for Injectable Fillers
This cross-sectional review used the US Food and Drug Administration's manufacturer and user facility device experience database to evaluate for complications from the use of soft-tissue fillers.
Lazy Pentagonal Wedge Resection of Eyelid Margin Lesions
This Surgical Pearl describes a modified curvilinear or "lazy" pentagonal wedge resection technique to achieve the tarsal alignment associated with the pentagonal wedge minimize scarring and dog-ear deformity.
Spreader and Butterfly Graft Comparison in Cadaveric Models
This cadaver study uses computational fluid dynamics to compare nasal airflow resistance following butterfly and spreader graft surgical interventions for treating nasal valve compromise.
Blast SMS and Enrollment for Cleft Lip and Cleft Palate Surgery in Zimbabwe
This study tested the effectiveness of a "blast" short message service text message to facilitate enrollment with a visiting surgical team in Zimbabwe.
3-D Analysis of Fat-Processing Techniques for Facial Fat Grafting
This randomized clinical trial uses 3-dimensional volumetric analysis to assess which of 3 fat-processing techniques results in better volume retention in recipient sites in autologous fat grafting to correct facial asymmetry.
A Closer Look at the Analgesic Regimen After Rhinoplasty
To the Editor We read with great interest the article of Patel and colleagues in a recent issue of the JAMA Facial Plastic Surgery. The authors performed a retrospective study of 62 patients who underwent rhinoplasty, and they proposed a multifaceted pain control program to manage postoperative pain and ascertain the balance between controlling pain and avoiding overprescribing narcotics. The authors should be commended for performing a study in an important topic (eg, opioid consumption) in patients undergoing outpatient surgery. The current emphasis on the need to improve postoperative pain using multimodal analgesic strategies makes the topic very relevant in perioperative medicine.
Scaffold-Assisted Artificial Hair Implantation in a Rat Model
This randomized prospective animal study tests the biocompatibility of porous high-density polyethylene and expanded polytetrafluoroethylene hair-bearing scaffolds in rats.
Psoriatic Arthritis and the Dermatologist: An Approach to Screening and Clinical Evaluation
Publication date: Available online 21 April 2018
Source:Clinics in Dermatology
Author(s): Arianna Zhang, Drew JB Kurtzman, Lourdes M Perez-Chada, Joseph F Merola
Psoriatic arthritis is a common form of inflammatory arthritis that frequently accompanies psoriasis of the skin—up to 30% of patients with psoriasis are affected. Recognition of the clinical features of psoriatic arthritis is critical, as delayed detection and untreated disease may result in irreparable joint injury, impaired physical function, and a significantly reduced quality of life. Recent epidemiologic studies have also supported that psoriatic arthritis is associated with cardiometabolic and cerebrovascular comorbidities including coronary heart disease, diabetes mellitus, hypertension, dyslipidemia, and cerebrovascular accidents, further highlighting the importance of identifying affected patients. Dermatologists are poised for the early detection of psoriatic arthritis, as psoriasis predates its development in as many as 80% of patients. In an effort to further acquaint dermatologists and other clinicians with psoriatic arthritis, this review provides a detailed overview, emphasizing its salient clinical features, and discusses classification criteria, validated screening tools, and simple musculoskeletal examination maneuvers that may facilitate earlier detection and treatment of the disorder.
Damien de Veuster (1840–1889) – A Life Devoted to Lepers
Publication date: Available online 17 May 2018
Source:Clinics in Dermatology
Author(s): Jakub Pawlikowski, Joanna Banasiuk, Jarosław Sak, Mariusz Jojczuk, Andrzej Grzybowski
Father Damian de Veuster or Saint Damien of Molokai (1840–1889) was one of the precursors of the holistic approach to care provision for leprosy patients and contributed to the overcoming of patients' social stigmatization. He devoted his life to the lepers living in America's only leper colony, on the Hawaiian island of Molokai, where people with leprosy were required to live under government-sanctioned medical quarantine. Father Damien gained practical skills in caring for the sick, eagerly learning wound cleansing, bandaging techniques and drug administration from a nurse. Mahatma Gandhi said that Father Damien's work had inspired his own social campaigns in India.
Project-based learning methodology in the area of microbiology applied to undergraduate medical research
Abstract
In the recent years, there has been a decrease in the number of medical professionals dedicated to a research career. There is evidence that students with a research experience during their training acquire knowledge and skills that increase the probability of getting involved in research more successfully. In the Degree of Medicine (University of the Basque Country) the annual core subject 'Research Project' introduces students to research. The aim of this work was to implement a project-based learning methodology, with the students working on microbiology, and to analyse its result along time. Given an initial scenario, the students had to come up with a research idea related to medical microbiology and to carry out a research project, including writing a funding proposal, developing the experimental assays, and analyzing and presenting their results to a congress organized by the University. Summative assessment was performed by both students and teachers. A satisfaction survey was carried out to gather the students' opinion. The overall results regarding to the classroom dynamics, learning results and motivation after the implementation were favourable. Students referred a greater interest about research than they had before. They would choose the project based methodology versus the traditional one.Conformational plasticity of molecular chaperones involved in periplasmic and outer membrane protein folding
Abstract
How proteins reach their native conformation and location has been a major question of biology during the last 50 years. To counterbalance protein misfolding and the accumulation of aggregation products, a complex network of chaperones and proteases takes care of protein quality control in the cell. Such a chaperone network is in place in the periplasm of Gram-negative bacteria, where it is necessary for the survival of the bacteria as well as for outer membrane biogenesis. First mechanistic insights into the periplasmic chaperones that comprise this system came from crystal structures of their apo-states. While these crystal structures represent stable conformations of the proteins, they typically lack the information to understand the conformational changes that regulate the functional cycle as well as the mechanisms coordinating the dynamic adaptation of the chaperones to client proteins. During the past few years, the main actors of periplasmic and outer membrane protein folding have been extensively studied by a combination of experimental techniques. This review aims to give an overview of how recent structural biology developments have helped to achieve a better understanding of the functional cycles of the molecular chaperones Skp, SurA and BamA and how these cycles are regulated by dynamic conformational rearrangements.Deletion of PBP1a/LpoA complex compromises cell envelope integrity in Shewanella oneidensis
Abstract
High molecular weight penicillin binding proteins (PBPs) are responsible for the biosynthesis of peptidoglycan. In Escherichia coli, PBP1a and PBP1b form multienzyme peptidoglycan-synthesizing complexes with outer-membrane lipoproteins LpoA and LpoB, respectively. The two complexes appear to be largely redundant, although their distinct physiological roles remain unclear. PBP1a/LpoA and PBP1b/LpoB also exist in Shewanella oneidensis strain MR-1, but effects of the two complexes on aerobic growth and β-lactam resistance are quite different. In this study, the phenotypes of strains lacking a certain complex in S. oneidensis were compared. Deletion of PBP1a/LpoA caused aberrant cell morphology (including branches and bulges), enhanced sensitivity to various envelope stresses and outer membrane permeability. On the contrary, strains lacking PBP1b/LpoB displayed phenotypes similar to the wild type.A Study of the Focal Adhesion Kinase Inhibitor GSK2256098 in Patients with Recurrent Glioblastoma with Evaluation of Tumor Penetration of [11C]GSK2256098
Abstract
Background
GSK2256098 is a novel oral focal adhesion kinase inhibitor. Preclinical studies demonstrate growth inhibition in glioblastoma cell lines. However, rodent studies indicate limited blood-brain barrier penetration. In this expansion cohort within a phase I study, the safety, tolerability, pharmacokinetics and clinical activity of GSK2256098 were evaluated in patients with recurrent glioblastoma. Biodistribution and kinetics of [11C]GSK2256098 were assessed in a sub-study using positron-emission tomography (PET). Methods
Patients were treated with GSK2256098 until disease progression or withdrawal due to adverse events (AEs). Serial pharmacokinetic samples were collected on Day 1. On a single day between Days 9-20, patients received a microdose of intravenous [11C]GSK2256098 and scanned with PET over 90 minutes with parallel PK sample collection. Response was assessed by MRI every six weeks. Results
Thirteen patients were treated in three dose cohorts (1000 mg, 750 mg, 500 mg; all dosed twice-daily). The maximum tolerated dose was 1000 mg twice-daily. Dose-limiting toxicities were related to cerebral edema. Treatment-related AEs (>25%) were diarrhea, fatigue and nausea. Eight patients participated in the PET sub-study, with [11C]GSK2256098 VT estimates of 0.9 in tumor tissue, 0.5 in surrounding T2 enhancing areas, and 0.4 in normal brain,. Best response of stable disease was observed in three patients, including one patient on treatment for 11.3 months. Conclusions
GSK2256098 was tolerable in patients with relapsed glioblastoma. GSK2256098 crossed the blood-brain barrier at low levels into normal brain, but at markedly higher levels into tumor, consistent with tumor-associated blood-brain barrier disruption. Additional clinical trials of GSK2256098 are ongoing.An Active Role for Neurons in Glioma Progression: Making Sense of Scherer’s Structures
Abstract
Perineuronal satellitosis, the microanatomical clustering of glioma cells around neurons in the tumor microenvironment, has been recognized as a histopathological hallmark of high-grade gliomas since the seminal observations of Scherer in the 1930s. In this review, we explore the emerging understanding that neuron - glioma cell interactions regulate malignancy, and that neuronal activity is a critical determinant of glioma growth and progression. Elucidation of the interplay between normal and malignant neural circuitry is critical to realizing the promise of effective therapies for these seemingly intractable diseases. Here, we review current knowledge regarding the role of neuronal activity in the glioma microenvironment and highlight critical knowledge gaps in this burgeoning research space.Treatment of periorbital dark circles: Comparative study of carboxy therapy vs chemical peeling vs mesotherapy
Journal of Cosmetic Dermatology, EarlyView.
The role of Scalpel‐bougie cricothyroidotomy in managing emergency Front of Neck Airway access. A review and technical update for ENT surgeons
Clinical Otolaryngology, Volume 43, Issue 3, Page 791-794, June 2018.
Heterogeneity in skin manifestations of spotted fever group rickettsial infection in Australia
Australasian Journal of Dermatology, EarlyView.
Dermatoscopic chaos of border‐abruptness led to diagnosis of a minute melanoma
Australasian Journal of Dermatology, EarlyView.
A case of acitretin‐induced haemorrhagic lesions in Darier disease
Australasian Journal of Dermatology, EarlyView.
Trichoscopy helps to predict the time point of clinical cure of tinea capitis
Australasian Journal of Dermatology, EarlyView.
Bedside diagnosis of lentigo maligna with reflectance confocal microscopy
Journal of Cutaneous Pathology, EarlyView.
Dermatologic toxicity from novel therapy using antimicrobial peptide LL‐37 in melanoma: A detailed examination of the clinicopathologic features
Journal of Cutaneous Pathology, EarlyView.
Testicular choriocarcinoma with cutaneous metastasis in a 19‐year‐old man
Journal of Cutaneous Pathology, EarlyView.
Grocott methenamine silver and periodic acid‐Schiff positivity in cutaneous Mycobacterium avium complex infection
Journal of Cutaneous Pathology, EarlyView.
Nanoemulsions and dermatological diseases: contributions and therapeutic advances
International Journal of Dermatology, EarlyView.
A case of allergic contact dermatitis caused by Disperse Blue dye in ultrasound gel
Contact Dermatitis, EarlyView.
Contact dermatitis caused by dialkylcarbamoyl compounds in a medication used for chronic wounds
Contact Dermatitis, EarlyView.
Allergic contact dermatitis caused by plastic items containing the ultraviolet absorber drometrizole
Contact Dermatitis, EarlyView.
Angiosarcoma arising on the scalp in a Korean patient with xeroderma pigmentosum variant type
Photodermatology, Photoimmunology &Photomedicine, EarlyView.
Case of S100‐positive benign cephalic histiocytosis involving monocyte/macrophage lineage marker expression
The Journal of Dermatology, EarlyView.
Brodalumab‐induced palmar pustular eruption and joint swelling accompanied by muscle pains in two cases of psoriasis
The Journal of Dermatology, EarlyView.
Vertical transmission of herpes simplex virus: an update
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.
Painful circumscribed bullous dermatosis of the left hand after contact with African four‐toed hedgehogs
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.
Cutaneous metastatic breast cancer simulating angiosarcoma on the face and neck of a woman
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.
Are European dermatology patients treated unequally?
British Journal of Dermatology, Volume 178, Issue 5, Page 991-991, May 2018.
Allocation of biologics: health economics and clinical decision making in plaque psoriasis
British Journal of Dermatology, Volume 178, Issue 5, Page 997-998, May 2018.
After the approval of dupilumab for moderate‐to‐severe atopic dermatitis: what is next on the research agenda?
British Journal of Dermatology, Volume 178, Issue 5, Page 992-993, May 2018.
Beyond skin deep: taking bedside dermatology to the next level with noninvasive technologies
British Journal of Dermatology, Volume 178, Issue 5, Page 994-996, May 2018.
Changes in filaggrin degradation products and corneocyte surface texture by season
British Journal of Dermatology, Volume 178, Issue 5, Page e365-e365, May 2018.
U.K. Psychodermatology Society Annual Meeting, Royal College of Physicians, London, 26 January 2017
British Journal of Dermatology, Volume 178, Issue 5, Page e342-e346, May 2018.
U.K. Psychodermatology Society Annual Meeting, St Thomas’ Hospital, London, 25 January 2018
British Journal of Dermatology, Volume 178, Issue 5, Page e347-e353, May 2018.
Analysis of anti‐tumour necrosis factor‐induced skin lesions reveals strong T helper 1 activation with some distinct immunological characteristics
British Journal of Dermatology, Volume 178, Issue 5, Page e364-e364, May 2018.
Image Gallery: the new age of dermoscopy: optical super‐high magnification
British Journal of Dermatology, Volume 178, Issue 5, Page e330-e330, May 2018.
Iris pigmented lesions as a marker of cutaneous melanoma risk: an Australian case–control study
British Journal of Dermatology, Volume 178, Issue 5, Page e372-e372, May 2018.
Cellulitis: what to measure, how to define? Systematic review of outcomes from cellulitis trials
British Journal of Dermatology, Volume 178, Issue 5, Page 1000-1001, May 2018.
A systematic review of diagnostic criteria for psoriasis in adults and children: evidence from studies with a primary aim to develop or validate diagnostic criteria
British Journal of Dermatology, Volume 178, Issue 5, Page e362-e362, May 2018.
Supervised exercise training as an adjunct therapy for venous leg ulcers: a randomized controlled feasibility trial
British Journal of Dermatology, Volume 178, Issue 5, Page e361-e361, May 2018.
Inflammatory skin eruptions induced by anti‐tumour necrosis factor‐α therapy differ undeniably from psoriasis or eczema
British Journal of Dermatology, Volume 178, Issue 5, Page 1007-1008, May 2018.
Pembrolizumab treatment of a patient with xeroderma pigmentosum with disseminated melanoma and multiple nonmelanoma skin cancers
British Journal of Dermatology, Volume 178, Issue 5, Page 1009-1009, May 2018.
Adjunctive therapy for healing venous leg ulcers
British Journal of Dermatology, Volume 178, Issue 5, Page 1005-1006, May 2018.
Image Gallery: Cutaneous findings in Hunter syndrome
British Journal of Dermatology, Volume 178, Issue 5, Page e329-e329, May 2018.
Moving core outcome sets in dermatology forward
British Journal of Dermatology, Volume 178, Issue 5, Page 1010-1010, May 2018.
Dermatology on‐call should be commissioned and funded to support acute hospital services
Clinical and Experimental Dermatology, EarlyView.
Toll‐like receptor signalling induces the expression of serum amyloid A in epidermal keratinocytes and dermal fibroblasts
Clinical and Experimental Dermatology, EarlyView.
Paraneoplastic pemphigus foliaceus related to underlying breast cancer
Clinical and Experimental Dermatology, EarlyView.
Improvement in facial discoid dermatosis with calcipotriol/betamethasone ointment and low‐dose acitretin
Clinical and Experimental Dermatology, EarlyView.
Persistent unilateral ulcer of the ear as the first manifestation of relapsing polychondritis
Clinical and Experimental Dermatology, EarlyView.
Presence of human papillomavirus 16 in acral Bowen disease as a predictor of a less efficacious response to photodynamic therapy: a retrospective case series of nine patients
Clinical and Experimental Dermatology, EarlyView.
Patients affected by a new variant of endemic pemphigus foliaceus have autoantibodies colocalizing with MYZAP, p0071, desmoplakins 1–2 and ARVCF, causing renal damage
Clinical and Experimental Dermatology, EarlyView.
Lichenoid paraneoplastic pemphigus associated with follicular lymphoma without detectable autoantibodies
Clinical and Experimental Dermatology, EarlyView.
An enlarging pedunculated nodule on the shoulder of a 21‐year‐old man
Clinical and Experimental Dermatology, EarlyView.
Dermatological aspects of tularaemia: a study of 168 cases
Clinical and Experimental Dermatology, EarlyView.
Erythema nodosum arising during everolimus therapy for tuberous sclerosis complex
Pediatric Dermatology, EarlyView.
Therapeutic interventions to lessen the psychosocial effect of vitiligo in children: A review
Pediatric Dermatology, EarlyView.
Multiple superficial oral mucoceles after Mycoplasma‐induced mucositis
Pediatric Dermatology, EarlyView.
Cutaneous fibrolipomatous hamartoma: Report of 2 cases with retrocalcaneal location
Pediatric Dermatology, EarlyView.
Hand‐foot‐skin reaction related to use of the multikinase inhibitor sorafenib and hard orthotics
Pediatric Dermatology, EarlyView.
Risk factors for ocular complications in periocular infantile hemangiomas
Pediatric Dermatology, EarlyView.
Imprecise lexical superiority and the (slightly less) Repugnant Conclusion
Abstract
Recently, Derek Parfit has offered a novel solution to the "Repugnant Conclusion" that compared with the existence of many people whose quality of life would be very high, there is some much larger number of people whose existence would be better but whose lives would be barely worth living. On this solution, qualitative differences between two populations will often entail that the populations are merely "imprecisely" comparable. According to Parfit, this fact allows us to avoid the Repugnant Conclusion without violating the transitivity of better than. In this paper, I argue that Parfit's view nevertheless implies two objectionable conclusions. The first is an alternative version of the Repugnant Conclusion that, Parfit suggests, may not be all that repugnant. The second is a revised version of the first that is nearly identical to the Repugnant Conclusion. I conclude that Parfit's view offers no escape from repugnance.
Summary of historical terrestrial toxicity data for the brominated flame retardant tetrabromobisphenol A (TBBPA): effects on soil microorganisms, earthworms, and seedling emergence
Abstract
This article summarizes historical and recent research on the terrestrial toxicology of tetrabromobisphenol A (TBBPA). Despite its ubiquitous use and presence in the environment, little published data is available to evaluate the terrestrial ecotoxicity of TBBPA. The purposes of this paper are to enable broad access to a series of TBBPA ecotoxicity tests (nitrogen transformation, earthworm survival/reproduction, and seedling emergence/growth) that were conducted in support of regulatory risk assessments, and to summarize available research in the terrestrial toxicity of TBBPA. In these studies, no significant effect of TBBPA on nitrogen transformation was observed up to the highest concentration [1000 mg/kg dry weight (d.w.) soil]. The no-observed-effect concentrations (NOECs) for seedling emergence ranged from 20 to 5000 mg/kg d.w. Sensitivities were soybeans < corn ≈ onion ≈ tomato < ryegrass < cucumber; the most sensitive endpoints being seedling dry weight and height. The 28-day earthworm mortality NOEC was > 4840 mg/kg d.w. The most sensitive terrestrial endpoint was earthworm reproduction with a half maximal effective concentration (EC50) of 0.12 mg/kg d.w. soil. Based on this sensitive terrestrial endpoint, the EU derived a predicted no-effect concentration (PNEC) for soil of 0.012 mg/kg wet weight soil (EU 2008). We did not identify a more sensitive/lower point of departure for terrestrial toxicity endpoints in the published literature. On the basis of this PNEC, the EU concluded there was potential risk for environmental effects near TBBPA manufacturing sites, but no additional risk provided that no sewage sludge was applied to agricultural land (EU 2008).
Coordinated effects of lead toxicity and nutrient deprivation on growth, oxidative status, and elemental composition of primed and non-primed rice seedlings
Abstract
Rice crop is highly susceptible to the toxic levels of lead (Pb) during early growth stages. Moreover, a sufficient availability of mineral nutrients is critical for survival of plants particularly under stressful conditions. An experiment was carried out to unravel the coordinated effects of Pb stress (1-mM PbCl2) and different nutrient treatments (sufficient nutrient supply, nitrogen (N) deprivation, phosphorus (P) deprivation, and potassium (K) deprivation) on morphological growth, reactive oxygen species (ROS), antioxidants, and nutrient status in primed and non-primed rice seedlings. Seeding were primed with distilled water, 60-μM selenium, or 100-mg L−1 salicylic acid. Results indicated that Pb toxicity did not affect the root growth, but severely reduced the shoot growth (length and biomass) of rice in N- or P-deprived seedlings. Rice seedlings grown with sufficient supply of nutrients or K-deprivation showed no growth reduction under Pb toxicity. Exposure of Pb stress triggered the production of ROS (H2O2, O2˙−, OH−) and lipid peroxidation rate particularly under N- or P-deprivation. Moreover, the shoot accumulations of macronutrients (P in particular) were also restricted under Pb toxicity. Seed priming treatments effectively alleviated the undesirable effects of Pb stress on rice growth. The primed rice seedlings showed minimal oxidative damage caused by excessive generation of ROS under Pb stress and/or nutrient deprivation. Seed priming strengthened the antioxidative defense system of rice seedlings by regulating the activities/levels of superoxide dismutase, catalase, peroxidase, and glutathione in rice leaves. Moreover, better accumulation of essential nutrients in primed rice seedlings prevented the excess uptake and translocation of Pb, as evident by the lowered shoot accumulation of Pb.
Malignes Melanom − Früherkennung, Diagnostik und Nachsorge
Zusammenfassung
Hintergrund
Das maligne Melanom ist eine häufige Hautkrebsart mit einer sehr hohen Mortalität. In Europa versterben jährlich etwa 22.000 Menschen daran, davon etwa 2700 Patienten alleine in Deutschland. Die Inzidenz zeigt seit Jahren eine steigende Tendenz. Bedeutende Risikofaktoren für die Entstehung eines malignen Melanoms sind die Anzahl der melanozytären Nävi am Körper, eine positive Familienanamnese für Melanom und genetische Prädisposition.
Ziel
In dieser Arbeit soll auch dem Nichtdermatoonkologen eine Übersicht über die Diagnostik, Behandlung, Stadieneinteilung und Nachsorge des malignen Melanoms vermittelt werden.
Material und Methoden
Es wurde eine selektive Literaturrecherche in Medline über Pubmed erstellt und mit eigenen Erfahrungen der Autoren ergänzt.
Ergebnisse
Es werden 4 klinische Formen des Melanoms unterschieden: superfiziell spreitende Melanome (SSM), Lentigo-maligna-Melanome (LMM), akral-lentiginöse Melanome (ALM) und noduläre Melanome (NM). Diese unterscheiden sich sowohl in ihrem klinischen Erscheinungsbild, ihrer Lokalisation und Entwicklung und letztlich auch ihrer Prognose, die für das ALM und NM am ungünstigsten ist. Zur Diagnosesicherung und zur klinischen und pathologischen Stadieneinteilung ist eine operative Erstversorgung von kutanen Melanomen unerlässlich. Ab einer Tumordicke nach Breslow über 1 mm wird die diagnostische Exzision des Wächterlymphknotens (WLK) empfohlen. Bei Befall des WLK sollte zunächst eine Ausbreitungsdiagnostik mittels Schnittbildgebung erfolgen. Ist eine Exzision und Nachexzision und ggf. die WLK-Biopsie erfolgt, wird eine stadiengerechte Ausbreitungsdiagnostik empfohlen. Die empfohlene Nachsorge des malignen Melanoms gestaltet sich stadienadaptiert und entsprechend der aktuellen Leitlinie.
Correction to: Ecotoxicological assessment of oil-based paint using three-dimensional multi-species bio-testing model: pre- and post-bioremediation analysis
The original publication of this paper contains a mistake.
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Publication date: Available online 25 July 2018 Source: Journal of Photochemistry and Photobiology B: Biology Author(s): Marco Ballestr...
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Editorial AJR Reviewers: Heartfelt Thanks From the Editors and Staff Thomas H. Berquist 1 Share + Affiliation: Citation: American Journal...
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https://www.youtube.com/watch?v=DFOhpBjLqN4&t=1s , Η ΘΕΡΑΠΕΙΑ ΓΙΑ ΟΛΕΣ ΤΙΣ ΑΣΘΕΝΕΙΕΣ 1 Περιεχόμενα Σύντομο βιογραφικό Πρόλογος μεταφραστ...
