AbstractBackground.Young survivors of gastric cancer (GC) have better prognoses than elderly patients, yet their disease‐specific survival (DSS) has received little attention.Patients and Methods.Data on young patients (aged ≤40 years) with GC undergoing resections at three Chinese institutions (n = 542) and from the SEER database (n = 533) were retrospectively analyzed. Three‐year conditional disease‐specific survival (CS3) was assessed. The effects of well‐known prognostic factors over time were analyzed by time‐dependent Cox regression.Results.Overall, young Chinese patients with GC had a better 5‐year DSS than U.S. patients (62.8% vs. 54.1%; p < .05). The disease‐specific mortality likelihood of the entire cohort was not constant over time, with most deaths occurring during the first 3 years after surgery but peaking at 1 and 2 years in China and the U.S., respectively. Based on 5‐year survivorship, the CS3 rates of both groups were similar (90.9% [U.S.] vs. 91.5% [China]; p > .05). Cox regression showed that for Chinese patients, site, size, T stage, and N stage were independent prognostic factors at baseline (p < .05). For U.S. patients, grade, T stage. and N stage significantly affected DSS at baseline (p < .05). In both groups, only T stage continuously affected DSS within 3 years after gastrectomy. However, for both groups, the initial well‐known prognostic factors lost prognostic significance after 5 years of survival (all p > .05). Although the 5‐year DSS rates of young Chinese patients with T3 and T4a disease were significantly better than those of young U.S. patients, in each T stage, the CS3 of both regions trended toward consistency over time.Conclusion.For young patients with GC, the factors that predict survival at baseline vary over time. Although the initial 5‐year DSS is heterogeneous, insight into conditional survival will help clinicians evaluate the long‐term prognoses of survivors while ignoring population differences.Implications for Practice.With the increasing number of young survivors of gastric cancer (GC), it is essential for clinicians to understand the dynamic prognosis of these patients. Based on large data sets from China and the U.S, this study found that the prognostic factors that predict survival for young patients with GC at baseline vary over time. Although the initial 5‐year disease‐specific survival is heterogeneous, insight into conditional survival will help clinicians evaluate the long‐term prognoses of survivors while ignoring population differences. This knowledge may be more effective in helping young patients with GC to manage future uncertainties, especially when they need to make important life plans.
https://ift.tt/2BsRy6q
Παρασκευή 23 Νοεμβρίου 2018
Prognosis of Young Survivors of Gastric Cancer in China and the U.S.: Determining Long‐Term Outcomes Based on Conditional Survival
Concomitant Medications and Risk of Chemotherapy‐Induced Peripheral Neuropathy
AbstractBackground.Peripheral neuropathy is the dose‐limiting toxicity of many oncology drugs, including paclitaxel. There is large interindividual variability in the neuropathy, and several risk factors have been proposed; however, many have not been replicated. Here we present a comprehensive study aimed at identifying treatment and physiopathology‐related paclitaxel‐induced neuropathy risk factors in a large cohort of well‐characterized patients.Patients and Methods.Analyses included 503 patients with breast or ovarian cancer who received paclitaxel treatment. Paclitaxel dose modifications caused by the neuropathy were extracted from medical records and patients self‐reported neuropathy symptoms were collected. Multivariate logistic regression analyses were performed to identify concomitant medications and comorbidities associated with paclitaxel‐induced neuropathy.Results.Older patients had higher neuropathy: for each increase of 1 year of age, the risk of dose modifications and grade 3 neuropathy increased 4% and 5%, respectively. Cardiovascular drugs increased the risk of paclitaxel dose reductions (odds ratio [OR], 2.51; p = .006), with a stronger association for beta‐adrenergic antagonists. The total number of concomitant medications also showed an association with dose modifications (OR, 1.25; p = .012 for each concomitant drug increase). A dose modification predictive model that included the new identified factors gave an area under the curve of 0.74 (p = 1.07 × 10−10). Preexisting nerve compression syndromes seemed to increase neuropathy risk.Conclusion.Baseline characteristics of the patients, including age and concomitant medications, could be used to identify individuals at high risk of neuropathy, personalizing chemotherapy treatment and reducing the risk of severe neuropathy.Implications for Practice.Peripheral neuropathy is a common adverse effect of many cancer drugs, including chemotherapeutics, targeted therapies, and immune checkpoint inhibitors. About 40% of survivors of cancer have functional deficits caused by this toxicity, some of them irreversible. Currently, there are no effective treatments to prevent or treat this neuropathy. This study, performed in a large cohort of well‐characterized patients homogenously treated with paclitaxel, identified concomitant medications, comorbidities, and demographic factors associated with peripheral neuropathy. These factors could serve to identify patients at high risk of severe neuropathy for whom alternative non‐neurotoxic alternatives may be considered.
https://ift.tt/2KvO4mk
Initial Report of Second‐Line FOLFIRI in Combination with Ramucirumab in Advanced Gastroesophageal Adenocarcinomas: A Multi‐Institutional Retrospective Analysis
AbstractBackground.The randomized phase III RAINBOW trial established paclitaxel (pac) plus ramucirumab (ram) as a global standard for second‐line (2L) therapy in advanced gastric and gastroesophageal junction adenocarcinoma, together gastroesophageal adenocarcinoma (GEA). Patients (pts) receiving first‐line (1L) FOLFOX often develop neuropathy that renders continued neurotoxic agents in the 2L setting unappealing and other regimens more desirable. As such, FOLFIRI‐ram has become an option for patients with 2L GEA. FOLFIRI‐ramucirumab (ram) has demonstrated safety and activity in 2L colorectal cancer, but efficacy/safety data in GEA are lacking.Subjects, Materials, and Methods.Patients with GEA treated with 2L FOLFIRI‐ram between August 2014 and April 2018 were identified. Clinicopathologic data including oxaliplatin neurotoxicity rates/grades (G), 2L treatment response, progression‐free survival (PFS), overall survival (OS), safety, and molecular features were abstracted from three U.S. academic institutions. Kaplan‐Meier survival analysis was used to generate PFS/OS; the likelihood ratio test was used to determine statistical significance.Results.We identified 29 pts who received 2L FOLFIRI‐ram. All pts received 1L platinum + fluoropyrimidine, and 23 of 29 (79%) had post‐1L neuropathy; 12 (41%) had G1, and 11 (38%) had G2. Patients were evenly split between esophagus/gastroesophageal junction (12; 41%) and gastric cancer (17; 59%). Among evaluable pts (26/29), the overall response rate was 23% (all partial response) with a disease control rate of 79%. Median PFS was 6.0 months and median OS was 13.4 months among all evaluable pts. Six‐ and 12‐month OS were 90% (n = 18/20) and 41% (n = 7/17). There were no new safety signals.Conclusion.We provide the first data suggesting FOLFIRI‐ram is a safe, non‐neurotoxic regimen comparing favorably with the combination of pac + ram used in the seminal RAINBOW trial.Implications for Practice.Results of this study provide initial support for the safety and efficacy of second‐line (2L) FOLFIRI‐ramucirumab (ram) after progression on first‐line platinum/fluoropyrimidine in patients with gastroesophageal adenocarcinoma (GEA). The overall response, progression‐free survival, overall survival, and toxicity profile compare favorably with paclitaxel (pac) + ram and highlight the importance of the ongoing phase II RAMIRIS trial examining FOLFIRI‐ram versus pac + ram in 2L GEA (NCT03081143). FOLFIRI‐ram may warrant consideration for inclusion as an alternate regimen in consensus guidelines for GEA.
https://ift.tt/2BuEg9E
Biomarkers in Non-Complicated Pregnancy: Insights About Serum Myeloperoxidase and Ultrasensitive C-Reactive Protein
Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0777-2090
Introduction Pregnancy is characterized by increased innate immune response, with low-grade systemic inflammation. The specific role of MPO during normal pregnancy remains not well understood. Therefore, the aim of this study was to evaluate plasma levels of MPO, hs-CRP, total leukocyte, absolute neutrophil and monocyte counts, in all trimesters of normal human pregnancy compared with non-pregnant controls. In addition, possible fluctuations of MPO according to different inflammatory conditions in the normal gestation were studied. Materials and methods Case-control study (n=84) developed with 63 normal pregnant women and 21 healthy non-pregnant women. Total leukocyte, absolute neutrophils and absolute monocytes count, hs-CRP and MPO were measured in non-pregnant women and normal human pregnancy. They were evaluated according to the 3 trimesters of pregnancy and systemic low grade inflammatory status, which was identified through increased hs-CRP levels. Results MPO levels in the normal pregnant women were not elevated in every 3 trimesters of pregnancy (P=0.456) or in systemic inflammation (P=0.446). The hs-CRP levels, total leukocyte, absolute neutrophil and monocyte counts are present in higher concentrations in normal pregnant women in relation to non-pregnant women. Conclusions The MPO did not show fluctuations in plasma levels during the 3 trimesters of gestation or in relation to different inflammation conditions. Considering MPO and hs-CRP levels are changed in high cardiovascular risk conditions and MPO levels (unlike hs-CRP) didn't increase during non complicated pregnancy, MPO could be a better biomarker than hs-CRP to monitor these patients.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2AkFySv
Advanced Adrenocortical Carcinoma – What to do when First-Line Therapy Fails?
Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0715-1946
Adrenocortical carcinoma is a rare endocrine malignant disease with a generally unfavorable but heterogeneous prognosis. Although even in advanced stages a subset of patients experiences long-term disease stabilisation, effective systemic treatment options are limited. Mitotane is the only approved drug and the combination of etoposide, doxorubicin and cisplatin (plus mitotane) is currently considered as treatment standard for advanced adrenocortical carcinoma based on the results of a large randomized phase III trial. However, progression-free survival is often limited and further treatment options are frequently needed. Here we summarize the current knowledge about second and third-line therapeutic modalities (local and systemic) in advanced disease. Following the recent ESE-ENSAT guidelines local therapies play an important role for these patients. Regarding systemic therapies the best data are available for gemcitabine+capecitabine or streptozotocin (both with or without mitotane). Furthermore, we introduce our own approach to patients with advanced adrenocortical carcinoma based on our experience as a large multidisciplinary clinic dedicated to the care of patients with this orphan disease.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2TyGJXz
Commentary to accompany the paper: The Quality of Systematic Reviews Addressing Peripheral Nerve Repair and Reconstruction
The authors are to be commended for highlighting the need for further high quality evidence to assist surgical decision making in the management of nerve injuries and for encouraging critical appraisal of available studies. Whilst it cannot be the responsibility of the individual surgeon to undertake randomised control trials (RCTs) and systematically review (SR) all available literature it is our duty of care to ensure our knowledge is best updated and our privilege to safely action innovations in our field.
https://ift.tt/2Ra9f02
Biliary duct stenosis after image-guided high-dose-rate interstitial brachytherapy of central and hilar liver tumors
Abstract
Objective
Image-guided high-dose-rate interstitial brachytherapy (iBT) with iridium-192 is an effective treatment option for patients with liver malignancies. Little is known about long-term radiation effects on the bile duct system when central hepatic structures are exposed to iBT. This retrospective analysis investigates the occurrence of posthepatic cholestasis (PHC) and associated complications in patients undergoing iBT.
Materials and methods
We identified patients who underwent iBT of hepatic malignancies and had point doses of ≥1 Gy to central bile duct structures. Patients with known bile duct-related diseases or prior bile duct manipulation were excluded.
Results
102 patients were retrospectively included. Twenty-two patients (22%) developed morphologic PHC after a median of 17 (3–54) months; 18 of them were treated using percutaneous transhepatic cholangiopancreatography drainage or endoscopic retrograde cholangiopancreatography. The median point dose was 24.8 (4.4–80) Gy in patients with PHC versus 14.2 (1.8–61.7) Gy in those without PHC (p = 0.028). A dose of 20.8 Gy (biological effective dose, BED3/10 = 165/64.1 Gy) was identified to be the optimal cutoff dose (p = 0.028; 59% sensitivity, 24% specificity). Abscess/cholangitis was more common in patients with PHC compared to those without (4 of 22 vs. 2 of 80; p = 0.029). Median survival did not differ between patients with and without PHC (43 vs. 36 months; p = 0.571).
Conclusion
iBT of liver malignancies located near the hilum can cause PHC when the central bile ducts are exposed to high point doses. Given the long latency and absence of impact of iBT-induced PHC on median survival, the rate of cholestasis and complications seen in our patients appears to be acceptable.
https://ift.tt/2OZrX8F
Isotropically weighted intravoxel incoherent motion brain imaging at 7T
Publication date: Available online 23 November 2018
Source: Magnetic Resonance Imaging
Author(s): Ivan I. Maximov, Sebastian Vellmer
Abstract
Perfusion magnetic resonance imaging (MRI) is a promising non-invasive technique providing insights regarding the brain's microvascular architecture in vivo. The scalar perfusion metrics can be used for quantitative diagnostics of various brain abnormalities, in particular, in the stroke cases and tumours. However, conventional MRI-based perfusion approaches such as dynamic contrast-enhanced perfusion imaging or arterial spin labelling have a few weaknesses, for instance, contrast agent deposition, low signal-to-noise ratio, limited temporal and spatial resolution, and specific absorption rate constraints. As an alternative, the intravoxel incoherent motion (IVIM) approach exploits an extension of diffusion MRI in order to estimate perfusion parameters in the human brain. Application of IVIM imaging at ultra-high field MRI might employ the advantage of a higher signal-to-noise ratio, and thereby the use of higher spatial and temporal resolutions.
In the present work, we demonstrate an application of recently developed isotropic diffusion weighted sequences to the evaluation of IVIM parameters at an ultra-high 7T field. The used sequence exhibits high immunity to image degrading factors and allows one to acquire the data in a fast and efficient way. Utilising the bi-exponential fitting model of the signal attenuation, we performed an extensive analysis of the IVIM scalar metrics obtained by a isotropic diffusion weighted sequence in vivo and compared results with a conventional pulsed gradient sequence at 7T. In order to evaluate a possible metric bias originating from blood flows, we additionally used a truncated b-value protocol (b-values from 100 to 200 s/mm2 with the step 20 s/mm2) accompanied to the full range (b-values from 0 to 200 s/mm2). The IVIM scalar metrics have been assessed and analysed together with a large and middle vessel density atlas of the human brain. We found that the diffusion coefficients and perfusion fractions of the voxels consisting of large and middle vessels have higher values in contrast to other tissues. Additionally, we did not find a strong dependence of the IVIM metrics on the density values of the vessel atlas. Perspectives and limitations of the developed isotropic diffusion weighted perfusion are presented and discussed.
https://ift.tt/2Ksf2eQ
Sampling arterial input function (AIF) from peripheral arteries: Comparison of a temporospatial-feature based method against conventional manual method
Publication date: Available online 22 November 2018
Source: Magnetic Resonance Imaging
Author(s): Xiaowan Li, Christopher C. Conlin, Stephen T. Decker, Nan Hu, Michelle Mueller, Lillian Khor, Christopher Hanrahan, Gwenael Layec, Vivian S. Lee, Jeff L. Zhang
Abstract
It is often difficult to accurately localize small arteries in images of peripheral organs, and even more so with vascular abnormality vasculatures, including collateral arteries, in peripheral artery disease (PAD). This poses a challenge for manually sampling arterial input function (AIF) in quantifying dynamic contrast-enhanced (DCE) MRI data of peripheral organs. In this study, we designed a multi-step screening approach that utilizes both the temporal and spatial information of the dynamic images, and is presumably suitable for localizing small and unpredictable peripheral arteries. In 41 DCE MRI datasets acquired from human calf muscles, the proposed method took <5 s on average for sampling AIF for each case, much more efficient than the manual sampling method; AIFs by the two methods were comparable, with Pearson's correlation coefficient of 0.983 ± 0.004 (p-value < 0.01) and relative difference of 2.4% ± 2.6%. In conclusion, the proposed temporospatial-feature based method enables efficient and accurate sampling of AIF from peripheral arteries, and would improve measurement precision and inter-observer consistency for quantitative DCE MRI of peripheral tissues.
https://ift.tt/2BspQqv
Magnetic resonance imaging in the presence of projectiles and projectile fragments: Artefacts, image quality, rotation and movement
Publication date: Available online 22 November 2018
Source: Magnetic Resonance Imaging
Author(s): C. Hackenbroch, M. Wafa, S. Klinger, U.M. Mauer
Abstract
Background and purpose
Gunshot injuries have been considered a contraindication for MRI because of the risk of secondary dislodgement of retained metallic foreign bodies.
The objective of our study was to provide a systematic overview of the behaviour of projectiles and fragments in order to aid decision-making regarding the use of MRI in clinical practice.
Materials and methods
Ferromagnetic (n = 2) and non-ferromagnetic (n = 5) projectiles and fragments that were lodged in soft tissue (porcine masseter muscles) were examined using standard protocols at 1, 1.5 and 3 T, to simulate clinical situations as realistically as possible. CT was performed before and after every MRI to assess rotation and movement. Artefacts and image quality were analysed using Likert-type scales.
Results
Ferromagnetic projectiles were of poorer quality and showed larger artefacts and did not provide benefit for clinical practice compared to images of non-ferromagnetic material. Image quality of non-ferromagnetic projectiles varied widely (from very good to moderate) depending on the composition of the projectiles.
Field strength (1 T to 3 T) had no relevant influence on image quality.
Conclusions
Non-ferromagnetic projectiles are not a contraindication for MR imaging since there is no potential risk of secondary dislodgement. Image quality and the extent of artefacts, however, strongly depend on the type of ammunition used. The presence of ferromagnetic projectiles in or near vital anatomic structures is a contraindication for MRI because these objects may exhibit movement in response to magnetic fields. Knowledge of the type of projectile used appears to be important in order to guide patient management before an examination is performed.
https://ift.tt/2KseWnu
Brahma deficiency in keratinocytes promotes UV carcinogenesis by accelerating the escape from cell cycle arrest and the formation of DNA photolesions
Publication date: Available online 22 November 2018
Source: Journal of Dermatological Science
Author(s): Andrew W. Farrell, Gary M. Halliday, J. Guy Lyons
Abstract
Background
Ultraviolet radiation (UVR) is the principal cause of keratinocyte skin cancers. Previous work found that levels of the chromatin remodelling protein, Brahma (Brm), are diminished during the progression from actinic keratoses to cutaneous squamous cell carcinomas in humans, and its loss in UV-irradiated mouse skin causes epidermal hyperplasia and increased tumour incidence.
Methods
The skins of mice and mouse and human keratinocytes deficient in Brm were exposed to UVR and evaluated for cell cycle progression and DNA damage response.
Objective
To identify the mechanisms by which loss of Brm contributes to UVR-induced skin carcinogenesis.
Results
In both mouse keratinocytes and HaCaT cells, Brm deficiency led to an increased cell population growth following UVR exposure compared to cells with normal levels of Brm. Cell cycle analysis using a novel assay showed that Brm-deficient keratinocytes entered cell cycle arrest normally, but escaped from cell cycle arrest faster, enabling them to begin proliferating earlier. In mouse keratinocytes, Brm primarily affected accumulation in G0/G1-phase, whereas in HaCaT cells, which lack normal p53, accumulation in G20/GM-phase was affected. Brm-deficient keratinocytes in mouse skin and human cell cultures also had higher levels of UVR-induced cyclobutane pyrimidine dimer photolesions. These effects occurred without any compensatory increase in DNA repair or cell death to remove photolesions or the cells that harbor them from the keratinocyte population.
Conclusion
The loss of Brm in keratinocytes exposed to UVR enables them to resume proliferation while harboring DNA photolesions, leading to an increased fixation of mutations and, consequently, increased carcinogenesis.
https://ift.tt/2PSLQnn
Atopic dermatitis at preschool age and contact allergy in adolescence: a population‐based cohort study
Abstract
Background
Atopic dermatitis (AD) is characterized by an impaired skin barrier that can allow enhanced penetration of allergens. It is not clear whether AD influences the risk of developing contact allergy.
Objectives
To examine the association between AD at preschool age and contact allergy at 16 years of age.
Methods
At 16 years of age, 2215 adolescents from the population‐based cohort BAMSE were included. These adolescents had been followed with repeated questionnaires regarding AD throughout childhood, and contact allergy was assessed by skin patch test at 16 years.
Results
AD at preschool age was associated with contact allergy to at least one of the tested substances at 16 years of age among boys (adjusted odds ratio [OR] 1.51, 95% confidence interval 1.03‐2.20), but not among girls (adjusted OR 0.77, 95% CI 0.54‐1.10). AD at preschool age was not associated with contact allergy to nickel in either boys or girls. In contrast, AD at preschool age was associated with contact allergy to fragrance mix I (adjusted OR 3.10, 95% CI 1.66‐5.80). This association was observed especially for AD at preschool age in combination with immunoglobulin E (IgE) sensitization to airborne or food allergens (adjusted OR 3.80, 95% CI 1.67‐8.61).
Conclusions
The results suggest that AD in early childhood may be associated with contact allergy to fragrances, but not to nickel, in adolescence.
This article is protected by copyright. All rights reserved.
https://ift.tt/2BrMvD6
Clinical features and outcomes of spitzoid proliferations in children and adolescents
Summary
Background
Spitzoid proliferations range from Spitz nevi to melanomas, and there are few studies describing clinical features and outcomes in the pediatric population.
Objectives
Determine clinical features and outcomes of a large pediatric cohort with histopathologically‐confirmed Spitz tumors.
Methods
Retrospective cohort study of Boston Children's Hospital patients younger than 20 years with a histopathologic diagnosis of spitzoid proliferation from 1/1/1994 – 10/23/2012.
Results
Five hundred ninety‐five patients with 622 spitzoid proliferations were identified [median age = 7.4 years, (25th, 75th) quartiles = (4.6, 11.7) years]. Five hundred twelve (82.3%) proliferations were typical, 107 (17.2.%) were atypical, and 3 (0.5%) were melanomas. Median age at biopsy was 7.4, 7.2, and 17.2 years, respectively, and there was a significant difference in age at biopsy for patients with typical or atypical proliferations versus melanoma (p<0.01). Among samples with positive margins (n = 153), 55.1% (54/98) of typical proliferations, 77.4% (41/53) of atypical proliferations, and 100.0% (2/2) of melanomas were re‐excised. Six patients had sentinel lymph node biopsy performed, with 3 patients demonstrating nodes positive for melanocytic cells. With median follow‐up of 4.1 years for the full cohort, there were no related deaths.
Conclusion
Spitz tumors have strikingly benign outcomes in the pediatric population, though this study is limited by low number of melanomas and restriction to a single pediatric institution. Aggressive management recommendations should be reconsidered for children and adolescents with banal‐appearing Spitz nevi, based upon the clinically indolent behavior in this cohort.
This article is protected by copyright. All rights reserved.
https://ift.tt/2Kue1mi
Endocrine and metabolic adverse effects of immune checkpoint inhibitors: an overview (what endocrinologists should know)
Abstract
Immune checkpoint inhibitors (ICIs) are novel anticancer agents, recently introduced with the aim of boosting the immune response against tumors. ICIs are monoclonal autoantibodies that specifically target inhibitory receptors on T cells: cytotoxic T lymphocyte antigen 4 (CTLA4), programmed death 1 (PD-1) and its ligand (PD-1L). ICIs also generate peculiar dysimmune toxicities, called immune-related adverse events (irAEs), that can potentially affect any tissue, and some may be life-threatening if not promptly recognized. The endocrine and metabolic side effects of ICIs are reviewed here, with a particular focus on their clinical presentation and management. They are among the most frequent toxicities (around 10%) and include hypophysitis, thyroid disorders, adrenalitis, and diabetes mellitus. Treatment is based on the replacement of specific hormone deficits, accompanied by immunosuppression (with corticosteroids or other drugs), depending on irAEs grade, often without the need of ICI withdrawal, except in more severe forms. Prompt recognition of endocrine and metabolic irAEs and adequate treatment allow the patients to continue a therapy they are benefiting from. Endocrinologists, as an integral part of the multidisciplinary oncologic team, need to be familiar with the unique toxicity profile of these anticancer agents. Practical recommendations for their management are proposed.
https://ift.tt/2FMFEbU
Efficacy and Safety of Brodalumab in Patients with Moderate-to-Severe Plaque Psoriasis and Skin of Color: Results from the Pooled AMAGINE-2/-3 Randomized Trials
Abstract
Background
Data on treatment outcomes in patients with psoriasis who have skin of color are limited. Brodalumab has shown efficacy in patients with moderate-to-severe plaque psoriasis.
Objective
Our objective was to evaluate the efficacy, safety, and health-related quality of life associated with brodalumab in patients with skin of color participating in two phase III, multicenter, randomized, double-blind, placebo- and active comparator–controlled studies (AMAGINE-2/-3).
Methods
Patients were self-categorized into racial subgroups (black, Asian, or white) or the non-mutually exclusive ethnic subgroup Hispanic/Latino. Patients were randomized to receive brodalumab 210 mg every 2 weeks (Q2W) or ustekinumab (45 mg in patients weighing ≤ 100 kg and 90 mg in patients weighing > 100 kg) for 52 weeks. Skin clearance was monitored using the Psoriasis Area and Severity Index (PASI) and Static Physician's Global Assessment (sPGA). Treatment-emergent adverse events (TEAEs) were summarized by treatment and racial and ethnic subgroup. Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI).
Results
During the 12-week induction phase, 613 patients received ustekinumab (black, n = 20; Asian, n = 24; white, n = 551; Hispanic/Latino, n = 68) and 1236 patients received brodalumab 210 mg Q2W (black, n = 36; Asian, n = 39; white, n = 1116; Hispanic/Latino, n = 132). At week 52, a total of 590 patients received continuous ustekinumab (black, n = 19; Asian, n = 23; white, n = 532; Hispanic/Latino, n = 64) and 339 patients were re-randomized to continue receiving brodalumab 210 mg Q2W (black, n = 10; Asian, n = 7; white, n = 308; Hispanic/Latino, n = 40). Among patients who received brodalumab 210 mg Q2W, skin clearance response rates were similar across racial and ethnic subgroups at week 12 and week 52; rates of 75%, 90%, and 100% improvement in PASI from baseline were also higher, as was sPGA score ≤ 1, than in patients who received ustekinumab across all racial and ethnic subgroups. Rates of TEAEs and ≥ 5-point improvement in DLQI score were similar across racial and ethnic subgroups.
Conclusions
Brodalumab 210 mg Q2W is well tolerated and efficacious across diverse racial and ethnic subgroups in patients with psoriasis, including black, Asian, white, and Hispanic/Latino patients.
Trial Registry
ClinicalTrials.gov identifier NCT01708603 (AMAGINE-2); NCT01708629 (AMAGINE-3).
https://ift.tt/2r130jy
A fatal case of Fournier’s gangrene during neoadjuvant radiotherapy for rectal cancer
Abstract
Purpose
To report the development of an ultimately fatal occurrence of Fournier's gangrene in a rectal cancer patient undergoing neoadjuvant radiotherapy without chemotherapy.
Methods
A 53-year-old male patient with G2 cT3 cN1a cM0 stage IIIB adenocarcinoma of the lower rectum and several comorbidities including ulcerative colitis was treated with 56 Gy to the primary tumor in 28 fractions because he declined the recommended simultaneous chemotherapy. He was also enrolled in the ketogenic diet arm of our KETOCOMP study, so that prospective measurements of blood parameters, quality of life, and body composition were made.
Results
The patient died 6 days after completion of radiotherapy due to septic shock associated with Fournier's gangrene reaching from the right buttock into the gluteal muscles and descending into the scrotum. In retrospect, there were several signs probably indicating the development of the gangrene: (i) a decline in bioelectrical phase angle; (ii) an accelerated weight and fat-free mass loss starting in the third week of radiotherapy; (iii) an increase in C-reactive protein (CRP) and concurrent drop in high-density lipoprotein (HDL) cholesterol and insulin-like growth factor(IGF)-1 concentrations; and (iv) the occurrence of a sharp pain in the perianal region reported in the fifth week of radiotherapy. Notably, his self-reported quality of life score was the same at the end of as before radiotherapy.
Conclusions
This case highlights the occurrence of Fournier's gangrene as an extremely rare but life-threatening complication during neoadjuvant radiotherapy for rectal cancer which should be refreshed in the awareness of radiation oncologists and radiologists.
https://ift.tt/2BrRtjg
Scholar : New articles have been published for Journal of Natural History, Volume 52, Issue 39-40
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High-Density Lipoprotein Components and Functionality in Cancer: State-of-the-Art
Publication date: Available online 22 November 2018
Source: Trends in Endocrinology & Metabolism
Author(s): Shiva Ganjali, Biagio Ricciuti, Matteo Pirro, Alexandra E. Butler, Stephen L. Atkin, Maciej Banach, Amirhossein Sahebkar
Cancer is the second leading cause of death in western countries, and thus represents a major global public health issue. Whilst it is well-recognized that diet, obesity, and smoking are risk factors for cancer, the role of low levels of high-density lipoprotein cholesterol (HDL-C) in cancer is less well appreciated. Conflicting evidence suggests that serum HDL-C levels may be either positively or negatively associated with cancer incidence and mortality. Such disparate associations are supported in part by the multitude of high-density lipoprotein (HDL) functions that can all have an impact on cancer cell biology. The aim of this review is to provide a comprehensive overview of the crosstalk between HDLs and cancer, focusing on the molecular mechanisms underlying this association.
https://ift.tt/2KqKiL1
Association between atopic dermatitis and extra-cutaneous bacterial and mycobacterial infections: A systematic review and meta-analysis
Publication date: Available online 22 November 2018
Source: Journal of the American Academy of Dermatology
Author(s): Linda Serrano, Kevin R. Patel, Jonathan I. Silverberg
Abstract
Background
Atopic dermatitis (AD) is associated with increased bacterial colonization and infection of skin, and multiple risk factors for extra-cutaneous infections. However, previous studies found conflicting results about whether AD is associated with increased extra-cutaneous infections.
Objectives
To determine whether extra-cutaneous bacterial and mycobacterial infections are increased in AD.
Methods
A systematic review was performed of all published observational studies with controls in MEDLINE, EMBASE, GREAT, Cochrane, and Web of Science that assessed extra-cutaneous infections in AD. Pooled meta-analysis was performed using random-effects weighting.
Results
Overall, 7 studies met inclusion criteria. All 7 studies found increased odds of at least one extra-cutaneous infection in AD, including endocarditis, meningitis, encephalitis, bone and joint infections, and sepsis. In pooled meta-analysis, AD in children and adults was associated with higher odds of ear infection (odds ratio [95% confidence interval]: 1.29 [1.16–1.43]), strep throat (2.31 [1.66–3.22]) and urinary tract infection (2.31 [1.66–3.22]), but not pneumonia (1.72 [0.75–3.98]). No publication bias was detected.
Limitations
Individual level data were not available.
Conclusions
AD patients have higher odds of extra-cutaneous infections. Future studies are needed to confirm these associations and determine their mechanisms.
https://ift.tt/2R6aTzz
Comment on “Trends in phototherapy utilization among Medicare beneficiaries in the United States, 2000 to 2015”
Publication date: Available online 22 November 2018
Source: Journal of the American Academy of Dermatology
Author(s): François Aubin, Eve Puzenat, Fabien Pelletier, Charlée Nardin, Florence Castelain
https://ift.tt/2PMPmiR
A review of smartphone applications for promoting sun protection practices
Publication date: Available online 22 November 2018
Source: Journal of the American Academy of Dermatology
Author(s): C. Moran, E. Zetler
https://ift.tt/2R6tT12
Facial Reconstruction After Mohs Surgery, 1st ed
Publication date: Available online 22 November 2018
Source: Journal of the American Academy of Dermatology
Author(s): Brian C. Leach
https://ift.tt/2PNaB4j
Time to Reconsider the Role of Sentinel Lymph Node Biopsy in Melanoma
Publication date: Available online 22 November 2018
Source: Journal of the American Academy of Dermatology
Author(s): M. Bigby, S. Zagarella, M. Sladden, C.M. Popescu
https://ift.tt/2R8cbdA
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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The online platform for Taylor & Francis Online content New for Canadian Journal of Remote Sen...
