A phase II trial of the effect of perindopril on hand–foot skin reaction (HFSR) incidence and severity in patients receiving regorafenib for refractory mCRC

Abstract

Purpose

Regorafenib is an oral multi-kinase inhibitor that offers an OS benefit to patients with mCRC refractory to standard therapy (Grothey et al., in Lancet 381:303–312, 2013), but comes with potential significant toxicities including grade 3 hand–foot skin reaction (HFSR). The pathogenesis of regorafenib-induced HFSR is not well established, but may be related to alterations in the capillary endothelium. We hypothesized that perindopril, an angiotensin-converting enzyme (ACE) inhibitor, indicated for the treatment of hypertension (Ceconi et al., in Cardiovasc Res 73:237–246, 2007), and which plays a role in preventing endothelial dysfunction, may help to prevent or reduce the severity of regorafenib-induced HFSR.

Patients and methods

In this single-center phase II open-label trial, patients with refractory mCRC were treated with both regorafenib (160 mg/day) and perindopril (4 mg/day) for 21 days per 28-day cycle. The primary end point was to assess the proportion of patients with any grade HFSR toxicity. Secondary end points included time to development of worst (grade 3) HFSR, reduction of all grades of hypertension and all grade toxicities, as well as progression-free survival. All toxicities were evaluated using CTCAE v4.03.

Results

A planned interim analysis was performed after ten evaluable patients had completed their first cycle of study treatment. As 50% (5/10) experienced grade 3 HFSR, enrolment was stopped as the addition of perindopril did not lead to a reduced level of HFSR compared with regorafenib alone. Other grade 3 toxicities included hypertension (16.7%) and increased AST (16.7%).

Conclusion

The addition of an ACE inhibitor perindopril to regorafenib did not reduce HFSR incidence or severity in patients with refractory mCRC.

https://ift.tt/2RD8m06

MnO 2 -loaded microorganism-derived carbon for U(VI) adsorption from aqueous solution

Abstract

A low-cost industrial microorganism, Saccharomyces cerevisiae, was employed as a precursor to synthesize carbon/MnO₂ composites (MMCs) via an oxidation-reduction reaction and one-step carbonization method for U(VI) adsorption. Scanning electron microscopy and nitrogen adsorption measurement indicated that the microorganism's carbonization could form surface porous structure and increase the specific surface area. Batch experiments showed that the maximum U(VI) adsorption capacity of MMCs reached 207 mg g⁻¹ at [U(VI)]_initial = 25 mg L⁻¹ and pH_initial = 4.5. The obtained thermodynamic and kinetic parameters suggested that the process is endothermic, spontaneous, and chemisorption. FTIR and X-ray photoelectron spectroscopy demonstrated that the surface hydroxyl groups of composites might be the reactive adsorption sites for U(VI). Additionally, 0.5 mol L⁻¹ HNO₃ solution could desorb ~ 95% uranium from U(VI)-loaded MMCs, and materials exhibited good regenerated availability. This study suggests that MMCs can be a potential adsorbent for U(VI) preconcentration and removal from radioactive wastewater.

https://ift.tt/2BXXB31

The Results of a Crossover Placebo-Controlled Study of the Effect of Lavender Oil on Behavioral and Psychological Symptoms of Dementia

Rejuvenation Research, Ahead of Print.


https://ift.tt/2Pp4ii5

Laryngeal temperature simulations during carbon dioxide laser irradiation delivered by a scanning micromanipulator

Abstract

We use scatter-limited phototherapy techniques to calculate the time-dependent temperature profiles of incisions made with a commercial carbon dioxide laser being used to make a 1-mm incision under computer control using the Digital Acublade™ and with incisions made with the same laser under manual control. The goal is to understand the differences in the amount of lateral thermal damage that is likely from the computer-controlled incisions versus the manually controlled incisions. The temperature profiles are calculated from the absorption and scatter of light in a homogeneous material. The resulting temperature profiles are presented as videos showing how the tissue heats up and cools down with the incident laser pulses. The time-dependent thermal distributions indicate that the computer-controlled laser incision could show as little as 210 μm of lateral thermal damage, whereas the manually controlled laser incisions could show as much as 375 μm of lateral thermal damage. The computer-controlled laser incision is able to control laser pulses fast enough that subsequent pulses can ablate away tissue with a significant amount of residual heat from the previous laser pulse. Using the scatter-limited phototherapy techniques, we can see how a computer-controlled laser can make incisions with less thermal damage by ablating away tissue holding a significant amount of heat from the previous pulse before it has time to diffuse through the tissue. This method of heat removal from laser incisions has not been previously described or demonstrated.

https://ift.tt/2PljBbH

5 natural ways to reduce breast size

Breast tissue is largely made up of fatty materials. Losing body fat is one effective way to reduce breast size naturally. In this article, we look at five methods people can use to reduce breast size, or the appearance of breasts.

https://ift.tt/2BWCJJn

Utilizing serum bicarbonate instead of venous pH to transition from intravenous to subcutaneous insulin shortens the duration of insulin infusion in pediatric diabetic ketoacidosis

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


https://ift.tt/2ryEwyF

Long-acting intramuscular ACTH stimulation test for the diagnosis of secondary adrenal insufficiency in children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


https://ift.tt/2G5Vxu6

Fatty pancreas in relation to insulin resistance and metabolic syndrome in children with obesity

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


https://ift.tt/2rpGPDO

Germinal center humoral autoimmunity independently mediates progression of allograft vasculopathy

Publication date: Available online 7 December 2018

Source: Journal of Autoimmunity

Author(s): M. Saeed Qureshi, Jawaher Alsughayyir, Manu Chhabra, Jason M. Ali, Martin J. Goddard, Chris Devine, Thomas M. Conlon, Michelle A. Linterman, Reza Motallebzadeh, Gavin J. Pettigrew

Abstract

The development of humoral autoimmunity following organ transplantation is increasingly recognised, but of uncertain significance. We examine whether autoimmunity contributes independently to allograft rejection.

In a MHC class II-mismatched murine model of chronic humoral rejection, we report that effector antinuclear autoantibody responses were initiated upon graft-versus-host allorecognition of recipient B cells by donor CD4 T-cells transferred within heart allografts. Consequently, grafts were rejected more rapidly, and with markedly augmented autoantibody responses, upon transplantation of hearts from donors previously primed against recipient. Nevertheless, rejection was dependent upon recipient T follicular helper (T_FH) cell differentiation and provision of cognate (peptide-specific) help for maintenance as long-lived GC reactions, which diversified to encompass responses against vimentin autoantigen. Heart grafts transplanted into stable donor/recipient mixed haematopoietic chimeras, or from parental strain donors into F1 recipients (neither of which can trigger host adaptive alloimmune responses), nevertheless provoked GC autoimmunity and were rejected chronically, with rejection similarly dependent upon host T_FH cell differentiation.

Thus, autoantibody responses contribute independently of host adaptive alloimmunity to graft rejection, but require host T_FH cell differentiation to maintain long-lived GC responses. The demonstration that one population of helper CD4 T-cells initiates humoral autoimmunity, but that a second population of T_FH cells is required for its maintenance as a GC reaction, has important implications for how autoimmune-related phenomena manifest.

https://ift.tt/2zNwfuZ

Poorly Differentiated Thyroid Cancer in the Context of the Revised 2015 American Thyroid Association Guidelines and the Updated American Joint Committee on Cancer/Tumor‐Node‐Metastasis Staging System (Eighth Edition)

SUMMARY

Objective

Poorly differentiated thyroid cancer (PDTC) is a rare, but aggressive thyroid cancer (TC) and a main cause of death from non‐anaplastic follicular cell‐derived TC. Assessing the risk of PDTC‐related death and the risk of recurrence is important for clinicians. The recent American Thyroid Association (ATA) 2015 guidelines and the updated 8^th edition of the American Joint Committee on Cancer/Tumor‐Node‐Metastasis (AJCC/TNM) staging system should support clinicians in the management approach to PDTC patients.

Patients

Forty‐six consecutive PDTC patients treated in a single oncologic center, 2000‐2017.

Measurements

Retrospective analysis of TNM stage, initial risk, response‐to‐therapy categories, follow‐up, and final disease status incorporating the ATA 2015 criteria and the 8^th AJCC/TNM staging system. Disease‐specific survival (DSS) using the Kaplan‐Meier method.

Results

Of the 46 PDTC 21 (45.6%) were ATA high risk (HR), 22 (47.8%), 17 (37%) and seven (15.2%) were TNM stage I, II, and III–IV, respectively. During a median follow‐up of 55.5 months, two (4.3%) patients were recurrent, 18 (39.1%) died of PDTC. The 5‐/10‐year DSS were 65/57%, respectively. According to the AJCC/TNM, the 5‐/10‐year DSS of I, II, and III‐IV stage were 83/83%; 77/55%, and 0/0%, respectively. According to the 2015 ATA initial risk, the 5‐/10‐year DSS were 91/72% for ATA intermediate risk, and 38/38% for ATA HR patients.

Conclusions

In PDTC patients, the updated AJCC/TNM staging system accurately predicts a high risk of death in stage III–IV, whereas it seems to be inadequate for predicting a very low or low risk of death expected for differentiated TC in stage I–II. The ATA initial HR may be also used to predict a high risk of PDTC‐related death.

This article is protected by copyright. All rights reserved.

https://ift.tt/2zOzsug

The healing of dental extraction sockets in insulin dependent diabetic patients: a prospective controlled observational study

Abstract

Background

The aim of this study was to determine whether there was a difference in delayed healing following dental extractions for insulin‐dependent diabetics as compared to non‐diabetic patients.

Methods

Prospective patients referred to the Adelaide Dental Hospital exodontia clinic for dental extractions were recruited into two groups: Known insulin‐dependent diabetics and healthy non‐diabetics. All had a random blood glucose level (BGL). Delayed healing cases were identified, and statistical evaluation performed.

Results

There were 56 insulin‐dependent diabetic patients (BGL 10.03, range 4.9‐26) and 49 non‐diabetic, age and sex matched, patients. Seven patients (12.5%) in the study group showed delayed healing following extraction, while only four patients (8.2%) in the control group suffered delayed healing. This difference was not statistically significant. Two of the study group developed post extraction infections, requiring incision, drainage, and antibiotics.

Conclusion

The study shows that Type 1 and insulin‐dependent Type 2 diabetic patients, if well controlled, tend to heal up well following dental extractions but with a small but not statistically different rate of post extraction complications including infection. This is contrary to what is usually taught. Clinicians should take great care with management of insulin dependent diabetic patients, as compared to non‐insulin dependent diabetics or non‐diabetic patients.

This article is protected by copyright. All rights reserved.

https://ift.tt/2Uq1G7x

Orofacial neuralgia associated with a middle cerebral artery aneurysm

Abstract

Chronic orofacial pain of neuropathic origin can present diagnostic and management dilemmas to dental practitioners and also affect the patient's quality of life. Intracranial aneurysms are a potential cause of stroke, with associated sub‐arachnoid haemorrhage leading to high rates of mortality and morbidity. A patient who had been previously managed for symptoms of temporomandibular joint disorder (TMD) presented with sharp, shooting pain of moderate intensity. It was precipitated by swallowing, and radiated to the right throat, posterior border of the mandible, ear and temporomandibular joint. Clinical and radiological investigations excluded odontogenic pain, TMD and other more common causes of facial pain. Magnetic resonance imaging revealed a 7 mm × 6 mm aneurysm in the right middle cerebral artery which was subsequently surgically clipped. Interestingly the facial pain resolved after this procedure. Compression of the insular region of the brain innervated by the trigeminal, glossopharyngeal and vagus nerves provides a plausible explanation for the pain. This is the first case of facial neuralgia associated with an aneurysm in the middle cerebral artery as far as we are aware, and it emphasizes the importance of a multidisciplinary approach in the diagnosis and management of unusual cases of chronic orofacial pain.

This article is protected by copyright. All rights reserved.

https://ift.tt/2AVqHym

Temporally Feathered Radiation Therapy (TFRT) for Head and Neck Squamous Cell Carcinoma

Condition:   Head and Neck Cancer
Intervention:   Radiation: Temporally Feathered Radiation Therapy (TFRT)
Sponsor:   Case Comprehensive Cancer Center
Not yet recruiting

https://ift.tt/2B0cFeY

Assement of the Morphological Characteristics of the Hips and Correlating Them With the Pathology Found

Conditions:   Ischiofemoral Impingement;   Hip Pain Chronic;   Musculoskeletal Disease;   Femoral Anteversion
Intervention:   Radiation: MRI
Sponsor:   Universidad de Zaragoza
Not yet recruiting

https://ift.tt/2B1QEMP

Cetuximab in Head and Neck Cancer Patients

Conditions:   Head and Neck Cancer;   Squamous Cell Carcinoma
Intervention:   Drug: Cetuximab
Sponsors:   University of Wisconsin, Madison;   National Cancer Institute (NCI);   National Institute of Dental and Craniofacial Research (NIDCR)
Not yet recruiting

https://ift.tt/2UmuFcc

Proximal Femoral Fractures - Patient Population, Risk Factors, Surgical Performance and Outcome

Condition:   Proximal Femoral Fracture
Interventions:   Procedure: surgery for pertrochanteric femoral fracture;   Procedure: surgery for femoral neck fracture
Sponsor:   University Hospital, Basel, Switzerland
Recruiting

https://ift.tt/2UmuwWc

Tabelecleucel in Combination With Pembrolizumab in Subjects With EBV+ Nasopharyngeal Carcinoma (ATA129-NPC-202)

Conditions:   Nasopharyngeal Carcinoma;   Nasopharyngeal Neoplasms;   Epstein-Barr Virus Infections;   Epstein-Barr Viraemia
Interventions:   Biological: tabelecleucel;   Biological: pembrolizumab
Sponsors:   Atara Biotherapeutics;   Merck Sharp & Dohme Corp.
Recruiting

https://ift.tt/2Upqr3p

Impact of Concurrent Task Performance on Transcranial Direct Current Stimulation (tDCS)-Induced Changes in Cortical Physiology and Working Memory

Publication date: Available online 7 December 2018

Source: Cortex

Author(s): Aron T. Hill, Nigel C. Rogasch, Paul B. Fitzgerald, Kate E. Hoy

Abstract

Transcranial direct current stimulation (tDCS) provides a means of non-invasively inducing plasticity-related changes in neural circuits in vivo and is experiencing increasing use as a potential tool for modulating brain function. There is growing evidence that tDCS-related outcomes are likely to be influenced by an individual's brain state at the time of stimulation, i.e., effects show a degree of 'state-dependency'. However, few studies have examined the behavioural and physiological impact of state-dependency within cognitively salient brain regions. Here, we applied High-Definition tDCS (HD-tDCS) over the left dorsolateral prefrontal cortex (DLPFC) in 20 healthy participants, whilst they either remained at rest, or performed a cognitive task engaging working memory (WM). In a third condition sham stimulation was administered during task performance. Neurophysiological changes were probed using TMS-evoked potentials (TEPs), event-related potentials (ERPs) recorded during n-back WM tasks, and via resting-state EEG (RS-EEG). From a physiological perspective, our results indicate a degree of neuromodulation following HD-tDCS, regardless of task engagement, as evidenced by changes in TEP amplitudes following both active stimulation conditions. Changes in ERP (P3) amplitudes were also observed for the 2-Back task following stimulation delivered during task performance only. However, no changes were seen on RS-EEG for any condition, nor were any group-level effects of either stimulation condition observed on n-back performance. As such, these findings paint a complex picture of neural and behavioural responses to prefrontal stimulation in healthy subjects and provide only limited support for state-dependent effects of HD-tDCS over the DLPFC overall.

https://ift.tt/2Pp6Rk4

Colored dots on Trichoscopy - Beware of artefacts

Publication date: Available online 6 December 2018

Source: Journal of the American Academy of Dermatology

Author(s): Sidharth Sonthalia

https://ift.tt/2E7tTu8

Electrodissection for Nevus Lipomatosus Cutaneous Superficialis Removal

Publication date: Available online 6 December 2018

Source: Journal of the American Academy of Dermatology

Author(s): Jesus Ancer-Arellano, Cesar Daniel Villarreal-Villarreal, Jesus Alberto Cardenas-de la Garza, Adrian Cuellar-Barboza, Osvaldo Vazquez-Martínez, Jorge Ocampo-Candiani

https://ift.tt/2Qy981l

Masculine Norms and Sunscreen Use among Adult Men in the United States: A cross-sectional study

Publication date: Available online 6 December 2018

Source: Journal of the American Academy of Dermatology

Author(s): Costner McKenzie, Alfred W. Rademaker, Roopal V. Kundu

https://ift.tt/2E5uD2M

Sphingolipids in the Pathogenesis of Parkinson’s Disease and Parkinsonism

Publication date: Available online 6 December 2018

Source: Trends in Endocrinology & Metabolism

Author(s): Guang Lin, Liping Wang, Paul C. Marcogliese, Hugo J. Bellen

The pathogenic mechanisms underlying Parkinson's disease (PD)/parkinsonism affect mitochondrial and endolysosomal trafficking. The retromer is required to retrieve some proteins from endosomes to the Golgi and plasma membrane. Here, we discuss how retromer-dependent retrieval also affects ceramide metabolism. Compelling studies across PD models in Drosophila and mammalian neurons reveal a pathogenic cascade implicating retromer dysfunction and mitochondrial defects. We argue that ceramides may play a critical role in the pathobiology based on the studies of PLA2G6 and VPS35 in Drosophila mutants and human knock-down cells. In addition, pathogenic variants in many lysosomal storage disorder genes have recently been associated with PD, suggesting a potential overlap between the pathogenic mechanisms underlying these disorders. We propose that disruption of ceramide metabolism may affect endolysosomal and mitochondrial function, and plays an important role in PD/parkinsonism.

https://ift.tt/2AZASSE

Mapping terrestrial oil spill impact using machine learning random forest and Landsat 8 OLI imagery: a case site within the Niger Delta region of Nigeria

Abstract

Terrestrial oil pollution is one of the major causes of ecological damage within the Niger Delta region of Nigeria and has caused a considerable loss of mangroves and arable croplands since the discovery of crude oil in 1956. The exact extent of landcover loss due to oil pollution remains uncertain due to the variability in factors such as volume and size of the oil spills, the age of oil, and its effects on the different vegetation types. Here, the feasibility of identifying oil-impacted land in the Niger Delta region of Nigeria with a machine learning random forest classifier using Landsat 8 (OLI spectral bands) and Vegetation Health Indices is explored. Oil spill incident data for the years 2015 and 2016 were obtained from published records of the National Oil Spill Detection and Response Agency and Shell Petroleum Development Corporation. Various health indices and spectral wavelengths from visible, near-infrared, and shortwave infrared bands were fused and classified using the machine learning random forest classifier to distinguish between oil-free and oil spill–impacted landcover. This provided the basis for the identification of the best variables for discriminating oil polluted from unpolluted land. Results showed that better results for discriminating oil-free and oil polluted landcovers were obtained when individual landcover types were classified separately as opposed to when the full study area image including all landcover types was classified at once. Similarly, the results also showed that biomass density plays a significant role in the characterization and classification of oil contaminated and oil-free pixels as tree cover areas showed higher classification accuracy compared to cropland and grassland.

https://ift.tt/2zKqEG0

Providing Evidence: Step by Step—a Letter from Associate Editor, Tobias Else, MD

https://ift.tt/2ro6Gw9

JAK Inhibitors for Atopic Dermatitis: An Update

Abstract

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. AD is driven by barrier dysfunction and abnormal immune activation of T helper (Th) 2, Th22, and varying degrees of Th1 and Th17 among various subtypes. The Janus kinase (JAK)–signal transducer and activator of transcription (STAT) and spleen tyrosine kinase (SYK) pathways are involved in signaling of several AD-related cytokines, such as IFN-γ, IL-4, IL-13, IL-31, IL-33, IL-23, IL-22, and IL-17, mediating downstream inflammation and barrier alterations. While AD is primarily Th2-driven, the clinical and molecular heterogeneity of AD endotypes highlights the unmet need for effective therapeutic options that target more than one immune axis and are safe for long-term use. The JAK inhibitors, which target different combinations of kinases, have overlapping but distinct mechanisms of action and safety profiles. Several topical and oral JAK inhibitors have been shown to decrease AD severity and symptoms. A review of the JAK and SYK inhibitors that are currently undergoing evaluation for efficacy and safety in the treatment of AD summarizes available data on a promising area of therapeutics and further elucidates the complex molecular interactions that drive AD.

https://ift.tt/2Qg9YjZ