True Low-Power Self-Locking Soft Actuators

Abstract

Natural double-layered structures observed in living organisms are known to exhibit asymmetric volume changes with environmental triggers. Typical examples are natural roots of plants, which show unique self-organized bending behavior in response to environmental stimuli. Herein, light- and electro-active polymer (LEAP) based actuators with a double-layered structure are reported. The LEAP actuators exhibit an improvement of 250% in displacement and hold an object three times heavier as compared to that in the case of conventional electro-active polymer actuators. Most interestingly, the bending motion of the LEAP actuators can be effectively locked for a few tens of minutes even in the absence of a power supply. Further, the self-locking LEAP actuators show a large and reversible bending strain of more than 2.0% and require only 6.2 mW h cm⁻² of energy to hold an object for 15 min at an operating voltage of 3 V. These novel self-locking soft actuators should find wide applicability in artificial muscles, biomedical microdevices, and various innovative soft robot technologies.

A self-locking soft actuator is developed that exhibits light and voltage sensitivity and is capable of locking its motion for a few minutes even without a power supply. The light- and electro-active polymer (LEAP) actuator demonstrates a large and reversible bending strain with only a few milliwatt hours of energy consumption to hold an object for 15 min.

http://ift.tt/2EfNk16

A High-Performance Optical Memory Array Based on Inhomogeneity of Organic Semiconductors

Abstract

Organic optical memory devices keep attracting intensive interests for diverse optoelectronic applications including optical sensors and memories. Here, flexible nonvolatile optical memory devices are developed based on the bis[1]benzothieno[2,3-d;2′,3′-d′]naphtho[2,3-b;6,7-b′]dithiophene (BBTNDT) organic field-effect transistors with charge trapping centers induced by the inhomogeneity (nanosprouts) of the organic thin film. The devices exhibit average mobility as high as 7.7 cm² V⁻¹ s⁻¹, photoresponsivity of 433 A W⁻¹, and long retention time for more than 6 h with a current ratio larger than 10⁶. Compared with the standard floating gate memory transistors, the BBTNDT devices can reduce the fabrication complexity, cost, and time. Based on the reasonable performance of the single device on a rigid substrate, the optical memory transistor is further scaled up to a 16 × 16 active matrix array on a flexible substrate with operating voltage less than 3 V, and it is used to map out 2D optical images. The findings reveal the potentials of utilizing [1]benzothieno[3,2-b][1]benzothiophene (BTBT) derivatives as organic semiconductors for high-performance optical memory transistors with a facile structure. A detailed study on the charge trapping mechanism in the derivatives of BTBT materials is also provided, which is closely related to the nanosprouts formed inside the organic active layer.

A high-performance organic optical memory array is developed based on the structural inhomogeneity of bis[1]benzothieno[2,3-d;2′,3′-d′]naphtho[2,3-b;6,7-b′]dithiophene organic semiconductors with charge trapping centers induced by the nanosprouts in the thin film. The flexible 16 × 16 array can encrypt and store 2D optical images. The findings reveal the potentials of utilizing [1]benzothieno[3,2-b][1]benzothiophene derivatives for high-performance optical memory transistors with a facile structure.

http://ift.tt/2EQy2AO

Achieving Insertion-Like Capacity at Ultrahigh Rate via Tunable Surface Pseudocapacitance

Abstract

The insertion/deinsertion mechanism enables plenty of charge-storage sites in the bulk phase to be accessible to intercalated ions, giving rise to at least one more order of magnitude higher energy density than the adsorption/desorption mechanism. However, the sluggish ion diffusion in the bulk phase leads to several orders of magnitude slower charge-transport kinetics. An ideal energy-storage device should possess high power density and large energy density simultaneously. Herein, surface-modified Fe₂O₃ quantum dots anchored on graphene nanosheets are developed and exhibit greatly enhanced pseudocapacitance via fast dual-ion-involved redox reactions with both large specific capacity and fast charge/discharge capability. By using an aqueous Na₂SO₃ electrolyte, the oxygen-vacancy-tuned Fe₂O₃ surface greatly enhances the absorption of SO₃²⁻ anions that majorly increase the surface pseudocapacitance. Significantly, the Fe₂O₃-based electrode delivers a high specific capacity of 749 C g⁻¹ at 5 mV s⁻¹ and retains 290 C g⁻¹ at an ultrahigh scan rate of 3.2 V s⁻¹. With a novel dual-electrolyte design, a 2 V Fe₂O₃/Na₂SO₃//MnO₂/Na₂SO₄ asymmetric supercapacitor is constructed, delivering a high energy density of 75 W h kg⁻¹ at a power density of 3125 W kg⁻¹.

Tunable chemical adsorption of redox anions is achieved by surface-modified Fe₂O₃ quantum dots anchored on graphene nanosheets, exhibiting greatly enhanced pseudocapacitance via fast dual-ion-involved redox reactions and fast charge/discharge capability. Significantly, the electrode achieves a high capacity up to 749 C g⁻¹ in the Na₂SO₃ electrolytes and retains 290 C g⁻¹ at an ultrahigh scan rate of 3.2 V s⁻¹.

http://ift.tt/2EeZBCG

Superhierarchical Cobalt-Embedded Nitrogen-Doped Porous Carbon Nanosheets as Two-in-One Hosts for High-Performance Lithium–Sulfur Batteries

Abstract

Lithium–sulfur (Li–S) batteries, based on the redox reaction between elemental sulfur and lithium metal, have attracted great interest because of their inherently high theoretical energy density. However, the severe polysulfide shuttle effect and sluggish reaction kinetics in sulfur cathodes, as well as dendrite growth in lithium-metal anodes are great obstacles for their practical application. Herein, a two-in-one approach with superhierarchical cobalt-embedded nitrogen-doped porous carbon nanosheets (Co/N-PCNSs) as stable hosts for both elemental sulfur and metallic lithium to improve their performance simultaneously is reported. Experimental and theoretical results reveal that stable Co nanoparticles, elaborately encapsulated by N-doped graphitic carbon, can work synergistically with N heteroatoms to reserve the soluble polysulfides and promote the redox reaction kinetics of sulfur cathodes. Moreover, the high-surface-area pore structure and the Co-enhanced lithiophilic N heteroatoms in Co/N-PCNSs can regulate metallic lithium plating and successfully suppress lithium dendrite growth in the anodes. As a result, a full lithium–sulfur cell constructed with Co/N-PCNSs as two-in-one hosts demonstrates excellent capacity retention with stable Coulombic efficiency.

A two-in-one approach with superhierarchical cobalt-embedded nitrogen-doped porous carbon nanosheets (Co/N-PCNSs) as stable hosts for both elemental sulfur and metallic lithium is developed to improve the performance of lithium–sulfur batteries. Benefiting from the unique structure and surface chemistry merits, a full lithium–sulfur cell constructed with Co/N-PCNSs as the two-in-one hosts demonstrates excellent capacity retention with stable Coulombic efficiency.

http://ift.tt/2ESpObC

Tough and Water-Insensitive Self-Healing Elastomer for Robust Electronic Skin

Abstract

An electronic (e-) skin is expected to experience significant wear and tear over time. Therefore, self-healing stretchable materials that are simultaneously soft and with high fracture energy, that is high tolerance of damage or small cracks without propagating, are essential requirements for the realization of robust e-skin. However, previously reported elastomers and especially self-healing polymers are mostly viscoelastic and lack high mechanical toughness. Here, a new class of polymeric material crosslinked through rationally designed multistrength hydrogen bonding interactions is reported. The resultant supramolecular network in polymer film realizes exceptional mechanical properties such as notch-insensitive high stretchability (1200%), high toughness of 12 000 J m⁻², and autonomous self-healing even in artificial sweat. The tough self-healing materials enable the wafer-scale fabrication of robust and stretchable self-healing e-skin devices, which will provide new directions for future soft robotics and skin prosthetics.

An extremely tough and water-insensitive self-healing elastomer crosslinked through multistrength hydrogen bonding interactions is described. The resultant crosslinking network in polymer film realizes exceptional mechanical properties such as notch-insensitive high stretchability (1200%), a high toughness of 12 000 J m⁻², and autonomous self-healing even in artificial sweat. The tough self-healing materials enable the wafer-scale fabrication of robust and stretchable self-healing e-skin devices.

http://ift.tt/2EeZrey

Monodisperse CNT Microspheres for High Permeability and Efficiency Flow-Through Filtration Applications

Abstract

Carbon nanotube (CNT)-based filters have the potential to revolutionize water treatment because of their high capacity and fast kinetics in sorption of organic, inorganic, and biological pollutants. To date, CNT filters either rely on CNTs dispersed in liquids, which are difficult to recover and cause safety concerns, or on CNT buckypaper, which offers high efficiency, but suffers from an intrinsic trade-off between filter permeability and capacity. Here, a new approach is presented that bypasses this trade-off and achieves buckypaper-like efficiency combined with filter-column-like permeability and capacity. For this, CNTs are first assembled into porous microspheres and then are packed into microfluidic column filters. These microcolumns exhibit large flow-through filtration efficiencies, while maintaining membrane permeabilities an order of magnitude larger then CNT buckypaper and specific permeabilities double that of activated carbon for similar flowrates (232 000 L m⁻² h⁻¹ bar⁻¹, 1.23 × 10⁻¹² m²). Moreover, in a test to remove sodium dodecyl sulfate (SDS) from water, these microstructured CNT columns outperform activated carbon columns. This improved filtration efficiency and permeability is an important step toward a broader implementation of CNT-based filtration devices.

Porous carbon nanotube (CNT) microspheres packed into microfluidic column filters offer high flow-through filtration efficiencies, while maintaining permeabilities an order of magnitude larger then CNT buckypaper. Moreover, these columns of CNT microspheres show a better efficiency at removing sodium dodecyl sulfate from water than activated carbon particles of similar size under the same flow conditions.

http://ift.tt/2sgqcxP

Atomically Dispersed Transition Metals on Carbon Nanotubes with UltraHigh Loading for Selective Electrochemical Carbon Dioxide Reduction

Abstract

Single-atom catalysts (SACs) are the smallest entities for catalytic reactions with projected high atomic efficiency, superior activity, and selectivity; however, practical applications of SACs suffer from a very low metal loading of 1–2 wt%. Here, a class of SACs based on atomically dispersed transition metals on nitrogen-doped carbon nanotubes (MSA-N-CNTs, where M = Ni, Co, NiCo, CoFe, and NiPt) is synthesized with an extraordinarily high metal loading, e.g., 20 wt% in the case of NiSA-N-CNTs, using a new multistep pyrolysis process. Among these materials, NiSA-N-CNTs show an excellent selectivity and activity for the electrochemical reduction of CO₂ to CO, achieving a turnover frequency (TOF) of 11.7 s⁻¹ at −0.55 V (vs reversible hydrogen electrode (RHE)), two orders of magnitude higher than Ni nanoparticles supported on CNTs.

A novel atomically dispersed transition-metal single-atom catalyst supported on CNTs is synthesized with atomic loading as high as 20 wt%, excellent selectivity, and activity for the electrochemical reduction of carbon dioxide.

http://ift.tt/2EtZ82Z

Polymer Solar Cells with 90% External Quantum Efficiency Featuring an Ideal Light- and Charge-Manipulation Layer

Abstract

Rapid progress in the power conversion efficiency (PCE) of polymer solar cells (PSEs) is beneficial from the factors that match the irradiated solar spectrum, maximize incident light absorption, and reduce photogenerated charge recombination. To optimize the device efficiency, a nanopatterned ZnO:Al₂O₃ composite film is presented as an efficient light- and charge-manipulation layer (LCML). The Al₂O₃ shells on the ZnO nanoparticles offer the passivation effect that allows optimal electron collection by suppressing charge-recombination loss. Both the increased refractive index and the patterned deterministic aperiodic nanostructure in the ZnO:Al₂O₃ LCML cause broadband light harvesting. Highly efficient single-junction PSCs for different binary blends are obtained with a peak external quantum efficiency of up to 90%, showing certified PCEs of 9.69% and 13.03% for a fullerene blend of PTB7:PC₇₁BM and a nonfullerene blend, FTAZ:IDIC, respectively. Because of the substantial increase in efficiency, this method unlocks the full potential of the ZnO:Al₂O₃ LCML toward future photovoltaic applications.

Highly efficient polymer solar cells based on nanopatterned ZnO:Al₂O₃ composite film achieve a peak external quantum efficiency up to 90% and a certified power conversion efficiency of 13.03%. Optical and electrical studies demonstrate enhanced light harvesting due to passivation- and dipole-induced suppression of charge recombination loss and broadband absorption enhancement.

http://ift.tt/2sk0MPJ

3D Graphene Fibers Grown by Thermal Chemical Vapor Deposition

Abstract

3D assembly of graphene sheets (GSs) is important for preserving the merits of the single-atomic-layered structure. Simultaneously, vertical growth of GSs has long been a challenge for thermal chemical vapor deposition (CVD). Here, vertical growth of the GSs is achieved in a thermal CVD reactor and a novel 3D graphene structure, 3D graphene fibers (3DGFs), is developed. The 3DGFs are prepared by carbonizing electrospun polyacrylonitrile fibers in NH₃ and subsequently in situ growing the radially oriented GSs using thermal CVD. The GSs on the 3DGFs are densely arranged and interconnected with the edges fully exposed on the surface, resulting in high performances in multiple aspects such as electrical conductivity (3.4 × 10⁴–1.2 × 10⁵ S m⁻¹), electromagnetic shielding (60 932 dB cm² g⁻¹), and superhydrophobicity and superoleophilicity, which are far superior to the existing 3D graphene materials. With the extraordinary properties along with the easy scalability of the simple thermal CVD, the novel 3DGFs are highly promising for many applications such as high-strength and conducting composites, flexible conductors, electromagnetic shielding, energy storage, catalysis, and separation and purification. Furthermore, this strategy can be widely used to grow the vertical GSs on many other substrates by thermal CVD.

3D graphene fibers (3DGFs) are successfully synthesized by vertically growing graphene sheets on polymer-derived carbon nanofibers carbonized in NH₃ using thermal chemical vapor deposition. The 3DGFs exhibit high electrical conductivity (3.4 × 10⁴–1.2 × 10⁵ S m⁻¹), electromagnetic shielding effectiveness (60 932 dB cm² g⁻¹), and superhydrophobicity and superoleophilicity, far superior to the existing 3D graphene materials.

http://ift.tt/2ErvV90

A Self-Powered Sensor Mimicking Slow- and Fast-Adapting Cutaneous Mechanoreceptors

Abstract

Highly efficient human skin systems transmit fast adaptive (FA) and slow adaptive (SA) pulses selectively or consolidatively to the brain for a variety of external stimuli. The integrated analysis of these signals determines how humans perceive external physical stimuli. Here, a self-powered mechanoreceptor sensor based on an artificial ion-channel system combined with a piezoelectric film is presented, which can simultaneously implement FA and SA pulses like human skin. This device detects stimuli with high sensitivity and broad frequency band without external power. For the feasibility study, various stimuli are measured or detected. Vital signs such as the heart rate and ballistocardiogram can be measured simultaneously in real time. Also, a variety of stimuli such as the mechanical stress, surface roughness, and contact by a moving object can be distinguished and detected. This opens new scientific fields to realize the somatic cutaneous sensor of the real skin. Moreover, this new sensing scheme inspired by natural sensing structures is able to mimic the five senses of living creatures.

Both the slow-adapting and the fast-adapting behavior in human somatosensing are mimicked. For this, an ion-channel system is devised along with an artificial receptor fabricated from a piezoelectric film. The sensing signals are measured without any external power, because the piezoelectric film and ion-channel system are self-powered for sensing, resembling biological sensory systems.

http://ift.tt/2sk0LeD

Molecularly Imprinted Porous Aromatic Frameworks and Their Composite Components for Selective Extraction of Uranium Ions

Abstract

Selective extraction of uranium from water has attracted worldwide attention because the largest source of uranium is seawater with various interference ions (Na⁺, K⁺, Mg²⁺, Ca²⁺, etc.). However, traditional adsorbents encapsulate most of their functional sites in their dense structure, leading to problems with low selectivity and adsorption capacities. In this work, the tailor-made binding sites are first decorated into porous skeletons, and a series of molecularly imprinted porous aromatic frameworks are prepared for uranium extraction. Because the porous architecture provides numerous accessible sites, the resultant material has a fourfold increased ion capacity compared with traditional molecularly imprinted polymers and presents the highest selectivity among all reported uranium adsorbents. Moreover, the porous framework can be dispersed into commercial polymers to form composite components for the practical extraction of uranium ions from simulated seawater.

Traditional adsorbents for the selective extraction of uranium have the disadvantages of low available surface areas, capacities, and selectivity. Thus, porous aromatic frameworks are decorated with tailor-made binding sites to obtain molecularly imprinted porous aromatic frameworks, which possess excellent capacities and selectivity due to more accessible porous spaces and the hierarchical porosity.

http://ift.tt/2EwSSYs

Leg length, sitting height, and body proportions references for achondroplasia: New tools for monitoring growth

Achondroplasia is the most common form of inherited disproportionate short stature. We report leg length, sitting height, and body proportion curves for achondroplasia. Seven centile format of sitting height, leg length, sitting height/leg length ratio, sitting height/height ratio, and head circumference/height ratio were estimated by the LMS method. The Q-test was applied to assess the goodness of fit. For comparison, centiles of sitting height and leg length were graphed using Argentine national growth references for achondroplasia and non-achondroplasia populations. The sample consisted of 342 children with achondroplasia (171 males, 171 females) aged 0–18 years. The median (interquartile range) number of measurements per child was 6 (3, 12) for sitting height and 8 (3, 13) for head circumference. Median leg length increased from 14 cm at age 1 week to 44 and 40 cm (males and females, respectively) in achondroplasia adolescents which is 3.5 cm shorter than non-achondroplasia children at age 1 week and, 38 cm shorter at adolescence. Median sitting height increased from 34 cm at birth to 86 and 81 in adolescents' boys and girls respectively, only 5 cm shorter than non-achondroplasia children. Sitting height/leg length decreased from 2.61 at birth to approximately 1.90 at adolescent. Median head circumference/height ratio decreased from 0.79 at birth to 0.46 at 18 years in both sexes. Growth of lower limbs is affected early in life and becomes more noticeable throughout childhood. The disharmonic growth between the less affected trunk and the severely affected limbs determine body disproportion in achondroplasia.

http://ift.tt/2H01WmX

The art and science of choosing efficacy endpoints for rare disease clinical trials

An important challenge in rare disease clinical trials is to demonstrate a clinically meaningful and statistically significant response to treatment. Selecting the most appropriate and sensitive efficacy endpoints for a treatment trial is part art and part science. The types of endpoints should align with the stage of development (e.g., proof of concept vs. confirmation of clinical efficacy). The patient characteristics and disease stage should reflect the treatment goal of improving disease manifestations or preventing disease progression. For rare diseases, regulatory approval requires demonstration of clinical benefit, defined as how a patient, feels, functions, or survives, in at least one adequate and well-controlled pivotal study conducted according to Good Clinical Practice. In some cases, full regulatory approval can occur using a validated surrogate biomarker, while accelerated, or provisional, approval can occur using a biomarker that is likely to predict clinical benefit. Rare disease studies are small by necessity and require the use of endpoints with large effect sizes to demonstrate statistical significance. Understanding the quantitative factors that determine effect size and its impact on powering the study with an adequate sample size is key to the successful choice of endpoints. Interpreting the clinical meaningfulness of an observed change in an efficacy endpoint can be justified by statistical methods, regulatory precedence, and clinical context. Heterogeneous diseases that affect multiple organ systems may be better accommodated by endpoints that assess mean change across multiple endpoints within the same patient rather than mean change in an individual endpoint across all patients.

http://ift.tt/2FVDPo3

Two de novo novel mutations in one SHANK3 allele in a patient with autism and moderate intellectual disability

SHANK3 encodes for a scaffolding protein that links neurotransmitter receptors to the cytoskeleton and is enriched in postsynaptic densities of excitatory synapses. Deletions or mutations in one copy of the SHANK3 gene cause Phelan-McDermid syndrome, also called 22q13.3 deletion syndrome, a neurodevelopmental disorder with common features including global developmental delay, absent to severely impaired language, autistic behavior, and minor dysmorphic features. By whole exome sequencing, we identified two de novo novel variants including one frameshift pathogenic variant and one missense variant of unknown significance in a 14-year-old boy with delayed motor milestones, delayed language acquisition, autism, intellectual disability, ataxia, progressively worsening spasticity of the lower extremities, dysmorphic features, short stature, microcephaly, failure to thrive, chronic constipation, intrauterine growth restriction, and bilateral inguinal hernias. Both changes are within the CpG island in exon 21, separated by a 375 bp sequence. Next generation sequencing of PCR products revealed that the two variants are most frequently associated with each other. Sanger sequencing of the cloned PCR products further confirmed that both changes were on a single allele. The clinical presentation in this individual is consistent with other patients with a truncating mutation in exon 21, suggesting that the missense change contributes none or minimally to the phenotypes. This is the first report of two de novo mutations in one SHANK3 allele.

http://ift.tt/2H2Tm71

International investigation of neurocognitive and behavioral phenotype in 47,XXY (Klinefelter syndrome): Predicting individual differences

47,XXY (KS) occurs in 1:650 male births, though less than 25% are ever identified. We assessed stability of neurocognitive features across diverse populations and quantified factors mediating outcome. Forty-four boys from the Netherlands (NL) and 54 boys from the United States (US) participated. The Wechsler Intelligence Scales assessed intellectual functioning; the ANT program evaluated cognitive function; and the CBCL assessed behavioral functioning. ANOVA was used for group comparisons. Hierarchical regressions assessed variance explained by each independent variable: parental education, timing of diagnosis, testosterone, age, and nationality. Parental education, timing of diagnosis, and hormonal treatment all played an important role in neurocognitive performance. The observed higher IQ and better attention regulation in the US group as compared to the NL group was observed with decreased levels of behavioral problems in the US group. Cognitive measures that were different between the NL and US groups, i.e., attention regulation and IQ scores, were also significantly influenced by external factors including timing of diagnosis, testosterone treatment, and parental education. On the ANT, a cognitive phenotype of 47,XXY was observed, with similar scores on 9 out of the 10 ANT subtests for the NL and US groups. This study lays additional features to the foundation for an algorithm linking external variables to outcome on various neurodevelopmental measures.

http://ift.tt/2G026sW

What We Do and Do Not Know About Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Woman’s Day

Chronic kidney disease (CKD) affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide,¹ and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women' s health and specifically their kidney health, on the community, and the next generations; as well as to strive to be more curious about the unique aspects of kidney disease in women, so that we may apply those learnings more broadly.

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Patient Experience With Care and Its Association With Adherence to Hypertension Medications

Abstract

BACKGROUND

Medication adherence is crucial to effective chronic disease management, yet little is known about the influence of the patient–provider interaction on medication adherence to hypertensive regimens. We aimed to examine the association between the patient's experience with care and medication adherence.

METHODS

We collected 2,128 surveys over 4 years from a convenience sample of hypertensive patients seeking care at three urban safety-net practices in upstate New York. The survey collected adherence measures using the Morisky Medication Adherence Scale (MMAS-8) and patient experience measures. We used regression models to adjust for age, gender, race/ethnicity, self-reported health status, and clustering by patients. The primary outcome was reporting of medium-to-high adherence (MMAS ≥ 6) vs. low adherence

RESULTS

A total of 62.5% of respondents reported medium-to-high medication adherence. The concern the provider demonstrated for patient questions or worries (adjusted odds ratio [AOR] 1.4; 95% confidence interval [CI] 1.1–1.7), provider efforts to include the patient in decisions (AOR 1.5; 95% CI 1.8–1.9), information given (AOR 1.3; 95% CI 1.0–1.6), and the overall rating of care received (AOR 1.4; 95% CI 1.1–1.8) were associated with higher medication adherence. The amount of time the provider spent was not associated with medication adherence (AOR 1.2; 95% CI 0.9–1.4). Medium-to-high medication adherence was in turn associated with increased hypertension control rates.

CONCLUSIONS

Overall, better experiences with care were associated with higher adherence to hypertension regimens. However, the amount of time the provider spent with the patient was not statistically associated with medication adherence, suggesting that the quality of communication may be more important than the absolute quantity of time.

http://ift.tt/2sllT4i

Adherence to Antihypertensive Therapy: A Missing Link Between Treatment and Outcomes

The metric of "adherence" simply captures concordance of patient's self management behavior with mutually agreed health care recommendations. With increasing burden of chronic diseases, adherence to pharmacological, and nonpharmacological measures has emerged as an essential reinforcer to treatment effectiveness. Alarmingly, poor adherence to antihypertensive medication (AHM) is fuelling the public health crisis of unsuccessfully treated hypertension, negatively impacting cardiovascular, cerebrovascular, and renal outcomes.¹ A study carried out in 5 European countries forecasted 6,553 fewer hypertensive complications with cost saving of €36 billion over a decade if 70% of patients take >80% of their AHM.² Indeed, poor adherence to blood pressure (BP) lowering medication cuts across various groups such as gender, race, marital status, comorbidities, and is not driven by one particular demographic or biopsychosocial stereotype. Research over last few decades had aptly dissipated the long held paternalistic belief of "blame the patient" for poor adherence.¹ WHO's multidimensional adherence model has broadly classified reasons for poor adherence into 5 domains—socioeconomic factors, health care team- and system-related factors, condition-related factors, therapy-related factors, and patient-related factors.¹ In this backdrop, study by Fortuna et al. in current issue evaluated the health care team- and system-related dimension highlighting importance of participatory patient provider management with shared decision making in optimizing adherence to AHM therapy.³ Using 8-item Morisky Medication Adherence Scale, 29.7% of patients reported high adherence (score 8), 32.8% reported moderate adherence (score 6–7), and 37.5% (score <6) reported low adherence and there was linear positive correlation between Morisky Medication Adherence Scale score and BP control rate. Notably, quality and not the quantity of time spent by health care provider in the care of hypertensive patient was significant predictor of adherence in their study. However, downside of their study includes an observational design, nonprobability sampling and overfitting the logistic regression model due to higher prevalence of dependent outcome. Moreover, among 3 components of adherence (initiation of therapy, day to day implementation of prescribed dosing, and long-term persistence with therapy), the current study only reported implementation bottlenecks between actual and prescribed antihypertensive therapy. Importantly, it is also reported that 5% of the hypertensive patients fail to initiate treatment after prescribing, nearly 10% skip their scheduled doses on a given day (half of them have "drug holiday" lapses of >3 days) and about 50% default within 1 year of treatment initiation.⁴ The summary of recent meta-analyses of studies evaluating adherence to AHM are tabulated in Table 1.

http://ift.tt/2EqpLpD

New Methods to Study the Microcirculation

Abstract

Essential hypertension is associated with structural alterations in the microvessels; in particular, an increase in the media thickness to internal lumen ratio of small resistance arteries (MLR) and a reduction in capillary density have been observed. The evaluation of the morphological characteristics of small resistance arteries in humans is challenging. The gold-standard method is generally considered to be the measurement by wire or pressure micromyography of MLR of subcutaneous small vessels obtained by local biopsies. However, noninvasive techniques for the evaluation of retinal arterioles were recently proposed; in particular, 2 approaches, scanning laser Doppler flowmetry (SLDF) and adaptive optics (AO), seem to provide useful information. Both of them provide an estimation of the wall to lumen ratio (WLR) of retinal arterioles. Moreover, a noninvasive measurement of basal and total capillary density may be obtained by videomicroscopy/capillaroscopy. It has been recently demonstrated that AO has a substantial advantage over SLDF in terms of evaluation of microvascular morphology, since WLR measured with AO is more closely correlated with the M/L of subcutaneous small arteries. The possibility to noninvasively assess in a reliable way, microvascular morphology in a clinical setting may represent a major advancement, since micromyography has substantial limitations in its application due to the local invasiveness of the procedure.

http://ift.tt/2sfiYu4

Unsweetening the Heart: Possible Pleiotropic Effects of SGLT2 Inhibitors on Cardio and Cerebrovascular Alterations in Resistant Hypertensive Subjects

Abstract

Resistant hypertension (RH) is a multifactorial disease associated with several target organ damage, such as microalbuminuria, left ventricular hypertrophy, and arterial stiffness. These subjects have high cardiovascular complications, especially when associated with diabetes condition. Sodium glucose cotransporter 2 (SGLT-2) inhibitors represent a new class of oral antidiabetic drugs that have shown positive effects in diabetics and even hypertensives subjects. Several studies demonstrated positive outcomes related to blood pressure levels, body weight, and glycemic control. Also found a reduction on microalbuminuria, cardiac and arterial remodeling process, and decrease in hospitalization care due heart failure. Despite these positive effects, the outcomes found for stroke were conflicted and tend neutral effect. Based on this, we sought to assess the pleiotropic effects of SGLT-2 inhibitors and the possible impact in RH subjects. In order to analyze the prospects of SGLT-2 inhibitors as a possible medication to complement the therapy manage of this high-risk class of patients.

http://ift.tt/2ErOdH0

Antihypertensive Medications and Falls in the Elderly

More than two-thirds of elderly persons (≥65 years) in the United States have hypertension.¹ In addition, prospective cohort studies have shown that aging is significantly associated with hypertension prevalence. For example, the Framingham Heart Study reported that the prevalence of hypertension increased from 27.3% in individuals <60 years to 74.0% in those >80 years.² As hypertension is a major risk factor for cardiovascular morbidities and mortalities, especially in the elderly, treating hypertension in older individuals is an important task for clinicians.

http://ift.tt/2sk1z39

The Association Between Serum Activin A Levels and Hypertension in the Elderly: A Cross-Sectional Analysis From I-Lan Longitudinal Aging Study

Abstract

BACKGROUND

Hypertension is an important risk factor for cardiovascular disease. Activin A, a member of the transforming growth factor-β cytokine family, has been shown to regulate blood pressure through the renin–angiotensin system. However, the relationship between activin A and blood pressure remains uncertain. The objective of this study was to determine whether serum activin A levels are associated with blood pressure.

METHOD

A total of 470 participants of I-Lan longitudinal Aging Study (ILAS) were eligible for this study. Serum levels of activin A were assessed by enzyme-linked immunosorbent assay. Cross-sectional analyses were performed, including comparisons of demographic characteristics, hypertensive status, and activin A levels.

RESULTS

Among the study participants (50% men, mean age, 69 years), 236 (50.2%) were hypertensive and 234 (49.8%) were normotensive. Hypertensive patients had significantly higher serum activin A levels than normotensives (normotensive vs. hypertensive: 507 ± 169 vs. 554 ± 176 pg/ml, mean ± SD, P < 0.001). All subjects were divided into 3 tertiles on the basis of serum activin A levels. Increasing tertiles of activin A were associated with higher systolic blood pressure (SBP), diastolic blood pressure and pulse pressure (PP) (all P < 0.001). After adjusting for all the potential confounding factors, serum activin A concentration was still significantly associated with SBP (P = 0.02) and PP (P = 0.03).

CONCLUSIONS

Serum activin A level was associated with SBP and PP. Further studies are required to assess their causal relationship and the clinical relevance.

http://ift.tt/2Eqt1RR

Single Pill Combinations as Initial Therapy in the Management of Hypertension: What is Taking you so Long?

In 2017, 2 respected hypertension guidelines, those of Hypertension Canada and those of the Latin American Society of Hypertension added another treatment to their listing of first line (initial) pharmacological therapy for hypertension.^1,2 This event, unlikely to be reported by CNN or Fox was still newsworthy for 2 reasons. First, it is the only new therapy added to that list in almost 2 decades (at least in Canada). Second, the therapy was one that had been used in hypertension for more than 50 years. The treatment? Single pill combinations (SPCs) of 2 antihypertensive drugs. The examination of the duration of time it took from the initial introduction of SPCs in therapy to their recognition as first line in an increasing number of countries (but not in the United States) is illustrative of the limitations of our current approach in the identification and implementation of best practices.

http://ift.tt/2snAuwi

Left Ventricular Hypertrophy and Coronary Artery Calcifications: A Dangerous Duet?

Hypertension is a leading risk factor for premature morbidity and mortality in developed and developing countries.¹ It is a common cause of cerebrovascular disease and a major contributor to the global burden of ischemic heart disease and heart failure.¹ Several cardiac alterations may be present in hypertensive patients, which include cardiac structural and functional changes (increased left ventricular [LV] mass, LV systolic and diastolic dysfunction, and impairment of coronary reserve), arrhythmias, and enlargement of left atrial and aortic root.² Within the array of such abnormalities, considerable attention has been paid to LV hypertrophy for its negative association with major cardiovascular events and survival.^3,4 LV hypertrophy, either diagnosed by ECG or echocardiography,^5,6 reflects a dangerous vicious circle characterized by endothelial dysfunction, intrinsic myocyte impairment, ischemia, myocardial fibrosis, and apoptosis.

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Identification of the Optimal Protocol for Automated Office Blood Pressure Measurement Among Patients With Treated Hypertension

Abstract

BACKGROUND

Automated office blood pressure (AOBP) involving repeated, unobserved blood pressure (BP) readings during one clinic visit is recommended for in-office diagnosis and assessment of hypertension. However, the optimal AOBP protocol to determine BP control in the least amount of time with the fewest BP readings is yet to be determined and was the aim of this study.

METHODS

One hundred and eighty-nine patients (mean age 62.8 ± 12.1 years; 50.3% female) with treated hypertension referred to specialist clinics at 2 sites underwent AOBP in a quiet room alone. Eight BP measurements were taken starting immediately after sitting and then at 2-minute intervals (15 minutes total). The optimal AOBP protocol was defined by the smallest mean difference and highest intraclass correlation coefficient (ICC) compared with daytime ambulatory BP (ABP). The same BP device (Mobil-o-graph, IEM) was used for both AOBP and daytime ABP.

RESULTS

Average 15-minute AOBP and daytime ABP were 134 ± 22/82 ± 13 and 137 ± 17/83 ± 11 mm Hg, respectively. The optimal AOBP protocol was derived within a total duration of 6 minutes from the average of 2 measures started after 2 and 4 minutes of seated rest (systolic BP: mean difference (95% confidence interval) 0.004(−2.21, 2.21) mm Hg, P = 1.0; ICC = 0.81; diastolic BP: mean difference 0.37(−0.90, 1.63) mm Hg, P = 0.57; ICC = 0.86). AOBP measures taken after 8 minutes tended to underestimate daytime ABP (whether as a single BP or the average of more than 1 BP reading).

CONCLUSIONS

Only 2 AOBP readings taken over 6 minutes (excluding an initial reading immediately after sitting) may be needed to be comparable with daytime ABP.

http://ift.tt/2sfiPH2

Intradialytic Hypertension Frequency and Short-Term Clinical Outcomes Among Individuals Receiving Maintenance Hemodialysis

Abstract

BACKGROUND

Intradialytic hypertension occurs in 5–20% of hemodialysis treatments. Observational data support an association between intradialytic hypertension and long-term mortality. However, the short-term consequences of recurrent intradialytic hypertension are unknown.

METHODS

Data were taken from a cohort of prevalent hemodialysis patients receiving treatment at a large United States dialysis organization on 1 January 2010. A retrospective cohort design with a 180-day baseline, 30-day exposure assessment, and 30-day follow-up period was used to estimate the associations between intradialytic hypertension frequency and 30-day outcomes. Intradialytic hypertension frequency was defined as the proportion of exposure period hemodialysis treatments with a predialysis to postdialysis systolic blood pressure rise >0 mm Hg. Multivariable Cox proportional hazards regression, adjusted for baseline clinical, laboratory, and dialysis treatment covariates, was used to estimate hazard ratios and 95% confidence intervals.

RESULTS

Of the 37,094 study patients, 5,242 (14.1%), 17,965 (48.4%), 10,821 (29.2%), 3,066 (8.3%) had intradialytic hypertension in 0%, 1–32%, 33–66%, and ≥67% of exposure period treatments, respectively. More frequent intradialytic hypertension was associated with incremental increases in 30-day mortality and hospitalizations. Patients with intradialytic hypertension in ≥67% (vs. 0%) of exposure period treatments had the highest risk of all-cause death, hazard ratio [95% confidence interval]: 2.57 [1.68, 3.94]; cardiovascular (CV) death, 3.68 [1.89, 7.15]; all-cause hospitalizations, 1.42 [1.26, 1.62]; CV hospitalizations, 1.71 [1.36, 2.15]; and volume-related hospitalizations, 2.25 [1.25, 4.04].

CONCLUSIONS

Among prevalent hemodialysis patients, more frequent intradialytic hypertension was incrementally associated with increased 30-day morbidity and mortality. Intradialytic hypertension may be an important short-term risk marker in the hemodialysis population.

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Correlation of Blood Pressure Variability as Measured By Clinic, Self-measurement at Home, and Ambulatory Blood Pressure Monitoring

Abstract

BACKGROUND

Blood pressure variability (BPV) has been postulated as a potential predictor of cardiovascular outcomes. No agreement exists as to which measurement method is best for BPV estimation. We attempt to assess the correlation between BPV obtained at the doctor's office, self-measurement at home (SMBP) and ambulatory BP monitoring (ABPM).

METHODS

Eight weekly clinic BP measurements, 2 SMBP series, and 1 24-hour ABPM recording were carried out in a sample of treated hypertensive patients. BPV was calculated using the SD, the "coefficient of variation" and the "average real variability." Determinants of short-, mid-, and long-term BPV (within each measurement method) were also calculated. The different BPV determinants were correlated "intramethod" and "intermethod" by linear regression test.

RESULTS

For the 104 patients (66.5 ± 7.7 years, 58.7% males), the ABPM BPV (SD, systolic/diastolic: 14.5 ± 3.1/9.8 ± 2.5 mm Hg) was higher than the SMBP (12.2 ± 9.8/7.4 ± 5.8 mm Hg; P < 0.001) and clinic BPV (10 ± 8.9/5.9 ± 4.9 mm Hg; P = 0.001). The main BPV correlation between methods was weak, with a maximum R² = 0.17 (P < 0.001) between clinic and SMBP systolic BPV. The "intramethod" correlation of BPV yielded a maximum R² = 0.21 (P < 0.001) between morning diastolic SMBP intershift/intermeans variability. The "intermethod" correlation of short-, mid-, and long-term BPV determinants was weak (maximum R² = 0.22, P < 0.001, between clinic intraday variability/SMBP morning intershift variability).

CONCLUSIONS

The "intramethod" and "intermethod" correlation between BPV determinants was weak or nonexistent, even when comparing determinants reflecting the same type of temporal BPV. Our data suggest that BPV reflects a heterogeneous phenomenon that strongly depends on the estimation method and the time period evaluated.

http://ift.tt/2sfiJiE

Left Ventricular Hypertrophy Predicts Cardiovascular Events in Hypertensive Patients With Coronary Artery Calcifications

Abstract

BACKGROUND

Coronary artery calcification (CAC) is associated with increased cardiovascular (CV) risk. Left ventricular hypertrophy (LVH) is an independent risk factor for CV events. Our aim was to estimate the relative CV risk of LVH in the presence of CAC.

METHODS

We included asymptomatic hypertensive patients who were enrolled in the calcification arm of the INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy). Patients had baseline echocardiography and computed tomography to assess CAC. The primary end-point was the first CV event.

RESULTS

Two hundred and fifty-two subjects (mean age 64.7 ± 5.5 years, 54% men) were followed for a mean of 13.3 ± 2.6 years. 72 patients (28.5%) had LVH and 159 patients (63%) had CAC. During follow up, 89 patients had a first CV event. The rate of CV events was higher in those with than in those without CAC (43.4% vs. 21.5%, P < 0.01) and in those with than in those without LVH (44% vs. 31.6%, P < 0.01). However, LVH had no effect on CV events in the absence of CAC, whereas LVH almost doubled the rate of CV events (61.4% vs. 36.5%, P < 0.01) in the presence of CAC. In comparison to patients without CAC and without LVH the hazard ratio for CV event in those with LVH was 1.46 (95% confidence interval [CI], 0.50–4.21) in those without CAC and 4.4 (95% CI, 2.02–9.56) in those with CAC.

CONCLUSIONS

LVH and CAC independently predict CV events in asymptomatic hypertensive patients. However, the risk of LVH is mainly observed in those with CAC.

http://ift.tt/2Es0ECK

Prevalence of Hypertension Defined by Central Blood Pressure Measured Using a Type II Device in a Nationally Representative Cohort

Abstract

OBJECTIVES

Central blood pressure (BP) can be used to define hypertension. A central BP approach may be more sensitive than a conventional brachial BP approach in detecting hypertension. We aimed to compare the 2 approaches in estimating the prevalence hypertension in a nationally representative population.

METHODS

A total of 2,742 adults older than 19 years participated in the 2013–2016 National Nutrition and Health Survey in Taiwan. Central and brachial BP were simultaneously measured using a cuff-based stand-alone central BP monitor purporting to measure invasive central BP (type II device). Central hypertension was defined by central systolic (SBP)/diastolic BP (DBP) ≥130 or 90 mm Hg or using antihypertensive medications, and brachial hypertension was defined by brachial SBP/DBP ≥140 or 90 mm Hg or using antihypertensive medications.

RESULTS

The World Health Organization-standardized and national weighted prevalence rates of central hypertension were 27.95% and 32.48%, respectively, and both were significantly higher than those of brachial hypertension (20.80% and 25.43%, both P < 0.001). The national weighted prevalence rates of concordant central and brachial hypertension, concordant central and brachial nonhypertension, isolated central hypertension, and isolated brachial hypertension were 25.13%, 67.22%, 7.35%, and 0.30%, respectively. Most subjects with the isolated central hypertension (97%) were within the range of brachial prehypertension, but only 38.0% of subject with brachial prehypertension had central hypertension.

CONCLUSION

Almost one-third of a nationally representative population had hypertension detected by a central BP approach. Hypertension detection using a conventional brachial BP approach may underestimate the prevalence of hypertension and result in a less effective hypertension control.

http://ift.tt/2sfiELS

Acute Response to a 2-Minute Isometric Exercise Test Predicts the Blood Pressure-Lowering Efficacy of Isometric Resistance Training in Young Adults

Abstract

BACKGROUND

This work aimed to explore whether different forms of a simple isometric exercise test could be used to predict the blood pressure (BP)-lowering efficacy of different types of isometric resistance training (IRT) in healthy young adults. In light of the emphasis on primary prevention of hypertension, identifying those with normal BP who will respond to IRT is important. Also, heightened BP reactivity increases hypertension risk, and as IRT reduces BP reactivity in patients with hypertension, it warrants further investigation in a healthy population.

METHODS

Forty-six young men and women (24 ± 5 years; 116 ± 10/ 68 ± 8 mm Hg) were recruited from 2 study sites: Windsor, Canada (n = 26; 13 women), and Northampton, United Kingdom (n = 20; 10 women). Resting BP and BP reactivity to an isometric exercise test were assessed prior to and following 10 weeks of thrice weekly IRT. Canadian participants trained on a handgrip dynamometer (isometric handgrip, IHG), while participants in the UK trained on an isometric leg extension dynamometer (ILE).

RESULTS

Men and women enrolled in both interventions demonstrated significant reductions in systolic BP (P < 0.001) and pulse pressure (P < 0.05). Additionally, test-induced systolic BP changes to IHG and ILE tests were associated with IHG and ILE training-induced reductions in systolic BP after 10 weeks of training, respectively (r = 0.58 and r = 0.77; for IHG and ILE; P < 0.05).

CONCLUSIONS

The acute BP response to an isometric exercise test appears to be a viable tool to identify individuals who may respond to traditional IRT prescription.

http://ift.tt/2Es0A5Y

Angiotensin Receptor Expression and Vascular Endothelial Dysfunction in Obstructive Sleep Apnea

Abstract

BACKGROUND

Obstructive sleep apnea (OSA) is associated with vascular endothelial dysfunction (VED) in otherwise healthy patients. The role of renin–angiotensin system (RAS) in the OSA induced VED is not well understood.

METHODS

Recently diagnosed OSA patients with very low cardiovascular disease (CVD) risk (Framingham score <5%) were studied at diagnosis and after 12 weeks of verified continuous positive airway pressure (CPAP) therapy. Participants underwent biopsy of gluteal subcutaneous tissue at baseline and after CPAP. Microcirculatory endothelial expression of angiotensin receptors type-1 (AT-1) and type-2 (AT-2) was measured in the subcutaneous tissue using quantitative confocal microscopy techniques. The ex-vivo effect of AT-1 receptor blockade (ARB) on endothelial superoxide production was also measured before and after CPAP treatment.

RESULTS

In OSA patients (n = 11), microcirculatory endothelial AT1 expression decreased from 873 (200) (fluorescence units) at baseline to 393 (59) units after 12 weeks of CPAP (P = 0.02). AT2 expression did not decrease significantly in these patients (479 (75) to 329 (58) post CPAP (P = 0.08)). The ex-vivo addition of the losartan to the microcirculatory endothelium resulted in decreased superoxide expression in the vascular walls from 14.2 (2.2) units to 4.2 (0.8) P < 0.001; while it had no effect on post-CPAP patient tissue (P = 0.64).

CONCLUSIONS

In OSA patients with no to minimal CVD risk, VED is associated with upregulation of AT-1 expression that is reversible with CPAP. Endothelial oxidative stress was reversible with ARB. RAS activation may play an important role in the development of early CVD risk in OSA patients.

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Echocardiographic Left Ventricular Reverse Remodeling After 18 Months of Antihypertensive Treatment in Stage I Hypertension. Results From the Prever-Treatment Study

Abstract

BACKGROUND

Antihypertensive treatment improves echocardiographic parameters of hypertensive target organ damage in stage II hypertension, but less is known about the effects in stage I hypertension.

METHODS

In a cohort study nested in the randomized double-blind trial PREVER-treatment, 2-dimensional echocardiograms were performed in 110 individuals, aged 54.8 ± 7.9 years-old, with stage I hypertension at baseline and after 18 months of treatment with chlorthalidone/amiloride or losartan.

RESULTS

At baseline, 66 (60%) participants had concentric remodeling. After antihypertensive treatment, systolic (SBP) and diastolic blood pressure (BP) were reduced from 141/90 to 130/83 mm Hg (P = 0.009). There was a significant reduction in left ventricular (LV) mass (LVM) index (82.7 ± 17.1 to 79.2 ± 17.5 g/m²; P = 0.005) and relative wall thickness (0.45 ± 0.06 to 0.42 ± 0.05; P < 0.001), increasing the proportion of participants with normal LV geometry (31% to 49%, P = 0.006). Left atrial (LA) volume index reduced (26.8 ± 7.3 to 24.9 ± 6.5 ml/m²; P = 0.001), and mitral E-wave deceleration time increased (230 ± 46 to 247 ± 67 ms; P = 0.005), but there was no change in other parameters of diastolic function. LVM reduction was significantly higher in the 2 higher tertiles of SBP reduction compared to the lower tertile.

CONCLUSIONS

Treatment of patients with stage I hypertension for 18 months promotes favorable effects in the LA and LV remodeling. This improvement in cardiac end-organ damage might be associated with reduction of long term clinical consequences of hypertensive cardiomyopathy, particularly heart failure with preserved ejection fraction.

http://ift.tt/2Es0ueC

Short-Term Blood Pressure Variability and Cognition in the Elderly: Mere Association or a Key Mechanism?

Many studies have been published on the consequences of high blood pressure (BP) on the brain and overall they show that, even without the occurrence of a stroke, hypertension in middle-age is associated with an increased risk of cognitive deterioration, cognitive decline over time, and ultimately dementia some decades later.^1–3

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Relationship Between Blood Pressure Variability and Cognitive Function in Elderly Patients With Good Blood Pressure Control

Abstract

BACKGROUND

Although higher blood pressure (BP) levels and BP variability have been associated with cognitive impairment, data are sparse regarding the relationship between BP variability and cognitive function in elderly patients with well BP control.

METHODS

We analyzed 232 ambulatory patients with one or more cardiovascular risk factors. All patients underwent ambulatory BP monitoring and the Japanese version of the Montreal Cognitive Assessment (MoCA-J).

RESULTS

The mean age was 77.7 ± 8.3 years; 33.6% were male, and 85.3% were taking antihypertensive drugs. The average 24-hour BP level was 118.7 ± 10.0/68.3 ± 6.4 mm Hg. When we divided the weighted SD of systolic BP (SBP) as a measure of BP variability into quartiles, the top quartile group (≥19.6 mm Hg) had a significantly lower total MoCA-J score (15.4 [95% confidence interval 14.2–16.7] vs. 17.9 [17.2–18.6], P = 0.001) and lower scores on several domains, visuoexecutive (2.2 [1.9–2.6] vs. 2.8 [2.6–2.9], P = 0.012), abstraction (1.0 [0.7–1.2] vs. 1.3 [1.1–1.4], P = 0.015), attention (2.8 [2.4–3.1] vs. 3.6 [3.4–3.8], P = 0.001), and naming (2.1 [1.9–2.3] vs. 2.5 [2.4–2.6], P = 0.001) than quartiles 1 through 3 combined, after adjustment for age and 24-hour SBP. These associations were not found in the quartiles of 24-hour SBP.

CONCLUSIONS

In elderly patients with well ambulatory BP control, higher BP variability but not average ambulatory BP level was associated with cognitive impairment.

http://ift.tt/2Erw3Fw

Lung cancer: a brief review of epidemiology and screening

Future Oncology, Ahead of Print.


http://ift.tt/2nUZsgM

Validating the total illness burden index for prostate cancer (TIBI-CaP) in men with castration-resistant prostate cancer: data from TRUMPET

Future Oncology, Ahead of Print.


http://ift.tt/2nNVJCF

Ultraearly assessed reperfusion status after middle cerebral artery recanalization predicting clinical outcome

Objectives

Mechanical thrombectomy has high evidence in stroke therapy; however, successful recanalization guarantees not a favorable clinical outcome. We aimed to quantitatively assess the reperfusion status ultraearly after successful middle cerebral artery (MCA) recanalization to identify flow parameters that potentially allow predicting clinical outcome.

Materials and Methods

Sixty-seven stroke patients with acute MCA occlusion, undergoing recanalization, were enrolled. Using parametric color coding, a post-processing algorithm, pre-, and post-interventional digital subtraction angiography series were evaluated concerning the following parameters: pre- and post-procedural cortical relative time to peak (rTTP) of MCA territory, reperfusion time, and index. Functional long-term outcome was assessed by the 90-day modified Rankin Scale score (mRS; favorable: 0-2).

Results

Cortical rTTP was significantly shorter before (3.33 ± 1.36 seconds; P = .03) and after intervention (2.05 ± 0.70 seconds; P = .003) in patients with favorable clinical outcome. Additionally, age (P = .005) and initial National Institutes of Health Stroke Scale score (P = .02) were significantly different between the patients, whereas reperfusion index and time as well as initially estimated infarct size were not. In multivariate analysis, only post-procedural rTTP (P = .005) was independently associated with favorable clinical outcome. 2.29 seconds for post-procedural rTTP might be a threshold to predict favorable clinical outcome.

Conclusions

Ultraearly quantitative assessment of reperfusion status after successful MCA recanalization reveals post-procedural cortical rTTP as possible independent prognostic value in predicting favorable clinical outcome, even determining a threshold value might be possible. In consequence, focusing stroke therapy on microcirculatory patency could be valuable to improve outcome.

http://ift.tt/2slgPgi

Response to ‘Comment on ‘‘Adjuvant Trastuzumab Therapy for Early HER2-Positive Breast Cancer in Iran: A Cost-Effectiveness and Scenario Analysis for an Optimal Treatment Strategy”’

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Usefulness of Rapiplug in nipple reconstruction to improve nipple projection

Background

The final stage of breast reconstruction after mastectomy for breast cancer is nipple reconstruction. However, a consistent and reliable method resulting in the most ideal aesthetic results has yet to be clarified. This study analysed the long-term outcomes of nipple reconstruction using Rapiplug.

Methods

Forty-one patients who underwent immediate breast reconstruction after mastectomy between January 2014 and February 2017 were enrolled. Nipple reconstruction was performed with C-V flap and Hammond flap, and hat-shaped Rapiplug was implanted at the flap core. Nipple projection and width were measured and nipple reduction rates were calculated immediately after and at 3, 6, and 12 months after surgery. Patient satisfaction was surveyed at the 12-month follow-up and compared with patient characteristics and other variables.

Results

Forty-one nipple reconstructions were performed in 41 patients. Most post-operative adverse events were resolved with conservative management, and revision was performed in only one case. The mean nipple projections were 8.9 ± 1.8, 7 ± 1.8, 5.6 ± 1.6 and 4.9 ± 1.6 mm immediately, and 3, 6 and 12 months after surgery, respectively, and the mean reduction rate of nipple size with reference to the size immediately after surgery was 22.2%, 37.2% and 44.7% at 3, 6 and 12 months after surgery, respectively. Patient satisfaction was 82.9% in overall outcome, and 85.3% of projection was good or excellent.

Conclusion

Rapiplug can improve the long-term preservation of nipple projection after nipple reconstruction and is considered to be consistent and reliable with good aesthetic outcomes and no severe complications.

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How to insert an internal seton for supralevator sepsis: an effective technique for complex fistulae

http://ift.tt/2nPrKKx

Sentinel lymph node mapping in liver resection for colorectal liver metastases

http://ift.tt/2nVfhEn

Pulmonary actinomycosis masquerading as lung cancer: keep it in mind

http://ift.tt/2nMQNO7

Variability of perioperative mortality of hepatic resection in Australia

Background

Hepatic resection is a relatively young and complex specialized procedure. A strong relationship between volume and perioperative mortality has been reported internationally. However, there has been no multicentre study into hepatic resection in Australia. This retrospective, population-based cohort study was conducted to determine national, state and territory based volume and perioperative mortality rates (POMRs).

Methods

Australian Institute of Health and Welfare data was interrogated for the Australian Classification of Health Intervention codes for hepatic resection defined as extended hemi-hepatectomy (30421), hemi-hepatectomy (30418), segmental hepatic resection (30415) and sub-segmental hepatic resection (30414). Logistic regression analysis was performed using the de-identified data to investigate trends and differences between states/territories. Mortality rates were risk adjusted for age, gender and public or private admission. The data set included patients who underwent hepatic resection in the financial years 2005/2006 to 2012/2013.

Results

The overall POMR for all types of hepatic resection was 1.6% (201/12 562). There was no significant change in POMR over time. However, there was significant variation between the states and territories with two states having significantly higher POMR for major hepatic resections (regional range: 1.3–3.8%). POMRs increased with age with the highest mortality seen in the 75–79 year age group. The POMR was lower in private than in public hospitals.

Conclusion

The results of this study confirm that the overall Australian POMR for major hepatic resection is similar to results reported internationally. National and state/territory POMR has not varied significantly over time. The significant variation between states/territories warrants further investigation.

http://ift.tt/2nYEcaf

Assessment of banana fruit handling practices and associated fungal pathogens in Jimma town market, southwest Ethiopia

Abstract

Banana fruits are highly perishable and affected by different microbial contaminates because ripe bananas are very perishable. One of the most important factors causing great economical loss of banana fruits is postharvest fungal diseases caused by lack of proper handling along postharvest chains. In line with this, the study was carried out to assess banana fruits handling practices and identify the major causal agents of postharvest fungal disease of banana fruits in Jimma town of bishishe market. Assessment was carried out using purposive sampling to select the study area, followed by simple random sampling to collect information on handling practices through observation and interview using pretested questioners. The survey result revealed that losses of banana fruits due to spoilage and physical injury were common problems for all fruit vendors. Practices such as lack of sanitation, temperature management, and improper packaging and transportation problems were identified among the common causes for observed losses. A total of 48 fruits were purposively selected from open market, wholesales and retailers and fruit damage, disease incidence, disease severity and identification of diseases causing fungal pathogen were conducted under laboratory. The highest fruit damage (56.2%) was recorded in sample taken from retailers' shop, and the associated disease incidence and severity were 54.2% and 34%, respectively. Morphological identification of pure culture revealed that anthracnose caused by Colletotrichum musae and crown rot caused by fusarium spp. are the most important disease causing agents and result in large percentage of fruit loss in Jimma town of bishishe market.

Careless handling during loading and unloading, lack of temperature management, and sanitation problems in the market were identified as the main factors favored fungal pathogens development and associated banana fruit losses.

http://ift.tt/2FYLiCI

Local condiments from fermented tropical legume seeds modulate activities of critical enzymes relevant to cardiovascular diseases and endothelial function

Abstract

Investigation into modulatory effects of local condiments produced from fermented legume (African locust bean and soybean) seeds on activities of enzymes relevant to endothelial function and cardiovascular disease (arginase, phosphodiesterase-5, acetylcholinesterase, and, ecto 5′-nucleotidase) in vitro was the focus of this study. The condiments were prepared according to traditional methods of fermentation. Thereafter, modulatory effects of aqueous extracts from the condiments on activities of the enzymes were subsequently carried out. Results showed the extracts significantly inhibited activities of arginase, phosphodiesterase-5 and acetylcholinesterase, while the activity of ecto 5′-nucleotidase was stimulated at sample concentrations tested. Thus, the observed enzyme modulatory properties exhibited by the condiments could be novel mechanisms to support their use as functional foods and nutraceuticals for the management of cardiovascular disease and associated endothelial dysfunction.

Investigation into modulatory effects of local condiments produced from fermented legume (African locust bean and soybean) seeds on activities of enzymes relevant to endothelial function and cardiovascular disease was the focus of this study.

http://ift.tt/2H0ZT27

Population pharmacokinetics of enoxaparin in early stage of pediatric liver transplantation

ABSTRACT

Aim

Preventing post liver transplantation (LT) hepatic artery and portal vein thrombosis includes enoxaparin administration. Enoxaparin pharmacokinetics (PK) has not been investigated in children following LT. We described an enoxaparin PK model in 22 children the first week following the LT.

Methods

Anti-Xa activity time-courses were analyzed using a nonlinear mixed effects approach with Monolix version 2016R.

Results

Anti-Xa activity time-courses were well described by a one-compartment model with first order absorption and elimination. Bodyweight prior the surgery (BW_PREOP) and the related postoperative variation (BW(t)) were the main covariates explaining CL and V between subject variabilities. Parameter estimates were CL_i = CL_TYP*(BW_PREOP/70)^3/4; V_i = V_TYP*(BW(t)/70)¹; where typical clearance (CL_TYP) and typical volume of distribution (V_TYP) were 1.23 L.h^-1 and 14.6 L, respectively. Standard dosing regimens of 50 IU/kg/12 h were insufficient to reach the target range of anti-Xa activity of 0.2 to 0.4 IU/mL. Specifically, seven children (32 %) did never attain the target range during the whole period of treatment and all children were at least once under dosed. According to the final results, we simulated individualized dosing regimens within 4 h following the first administration. More than 100 IU/kg/12 h are suggested to reach the target range of anti-Xa activity of 0.2 to 0.4 IU/mL from the first day.

Conclusion

Thanks to this model, the initial and maintenance doses could be assessed to rapidly achieve the target range. Higher doses per kg, especially in youngest children, are suggested.

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Use of trimethoprim–sulfamethoxazole during pregnancy and risk of spontaneous abortion: a nested case control study

Abstract

Aims

Data available on the fetal safety of trimethoprim–sulfamethoxazole exposure during pregnancy remains scarce and inconclusive. A previous study assessing the link between use TMP-SMX exposure during pregnancy and the risk of spontaneous abortion (SA) did not control for protopathic bias and indication bias.

Methods

We conducted a nested control study (n= 77 429 pregnancies including 7039 cases of SA and 70 390 controls) within the Quebec Pregnancy Cohort. For each case of SA, we selected 10 controls at the index date that were matched on gestational age and year of pregnancy. TMP-SMX exposure was defined as either having filled at least one prescription between the first day of gestation (1DG) and the index date, or as having filled a prescription before pregnancy but with a duration overlapping the 1DG (102 pregnancies exposed to TMP-SMX including 25 cases of SA and 77 controls).

Results

Adjusting for potential confounders, TMP-SMX exposure was associated with an increased risk of SA (AOR 2.94, 95% CI 1.89–4.57, 25 exposed cases). Similar results were found after controlling for indication bias and protopathic bias.

Conclusion

Given that this drug is widely use in HIV patients to prevent opportunistic infections and malaria, there is an urgent need to identify potential data sources in Africa for analysis of early pregnancy exposure to TMP-SMX

http://ift.tt/2EvZjuI

Acenocoumarol As An Alternative Anticoagulant In A Patient With Warfarin Related Nephropathy

Abstract

Adverse event

Warfarin related nephropathy

Drug implicated

Warfarin

The patient

A 31 year old female, managed with warfarin for rheumatic heart disease with atrial fibrillation.

Evidence that links the drug to the event

There were no alternative causes of nephropathy that could have caused the adverse event in this patient.

Management

Shifting the drug from warfarin to acenocoumarol

Mechanism, if known

Difference in renal elimination between warfarin and acenocoumarol

Implication for therapy

Clinicians should be aware of this rare adverse effect of warfarin and acenocoumarol can be considered as an alternative therapy for this condition.

Hypotheses to be tested

Further prospectively designed studies are needed to consider acenocoumarol as an alternative therapy in warfarin related nephropathy.

http://ift.tt/2sjHqKB

Demographic factors in Swedish adults undergoing root filling and subsequent extraction of a maxillary first molar: a comparative study

Abstract

Aim

To study the demographics of Swedish adults who had received a root filling, followed by extraction during the following 5 to 6 years in comparison to subjects who had undergone a corresponding root filling with an uneventful outcome.

Methodology

The root filled maxillary first molar was chosen as the comparison model. The Swedish Social Insurance Agency provided data on all teeth reported as root filled in Sweden during 2009. A comparison group, equally large as the study group, was constructed by randomly selecting subjects with root filled maxillary first molars which had not subsequently been extracted, i.e. an uneventful outcome. Demographic data on the subjects were obtained from Statistics Sweden: country of birth, disposable income, educational level, age, civil status and gender. Chi-square, T-tests and logistic regression were used for statistical analyses.

Results

In the year 2009, 36 139 maxillary first molar teeth were reported to have been root filled, 4 362 (12.1%) of which were then recorded as extracted during the following 5-6 year period.

Only minor inter-group differences were noted: 86.5% of the study group were Swedish born, compared with 84.4% of the comparison group (p=0.007). Women comprised 53.2% of the study group and 50.5% (p=0.01) of the comparison group. There was an association between extractions and gender as well as age; men had a lower odds ratio (OR) for extraction OR, 0.87; confidence interval (CI), 0.80-0.95. For every additional year the chance for extraction was higher OR, 1.01; CI, 1.01-1.01. No other significant differences were detected.

Conclusions

There was only little or no demographic differences between the study group, comprising Swedish adults who had undergone root filling of one of their maxillary first molars in 2009 and subsequent extraction during the following 5-6 years, and the comparison group, with uneventful outcomes after a corresponding root filling.

This article is protected by copyright. All rights reserved.

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Pretreatment neutrophil-to-lymphocyte ratio is associated with outcome of advanced-stage cancer patients treated with immunotherapy: a meta-analysis

Abstract

Background

To investigate the association between pretreatment blood neutrophil-to-lymphocyte ratio (NLR) and clinical outcomes for advanced-stage cancer patients treated with immunotherapy.

Methods

We conducted a comprehensive literature search to assess the relationship between pretreatment blood NLR and overall survival (OS) or progression-free survival (PFS) in advanced-stage cancer patients treated with immunotherapy. Published data including hazard ratios (HRs) and related 95% confidence interval (CI) were extracted. Pooled estimates of treatment outcomes were calculated using RevMan 5.3.5.

Results

Twenty-seven studies with 4647 patients were included in the current study. The pooled results suggested that high pretreatment blood NLR was correlated with significant shorter OS (HR = 1.98, 95% CI 1.66–2.36, P < 0.001) and PFS (HR = 1.78, 95% CI 1.48–2.15, P < 0.001). Subgroup analysis stratified by study targets revealed that anti-VEGF/VEGFR therapy (HR = 2.04, 95% CI 1.61–2.60, P < 0.001) and immune checkpoints blockade (HR = 2.16, 95% CI 1.86–2.51, P < 0.001) were significantly associated with inferior OS while other targets (HR = 1.63, 95% CI 0.89–2.99, P = 0.120) were not associated with OS. There was no correlation between distinct NLR cutoff values and OS ( \({r^}}\) = 0.218, P = 0.329) or PFS benefit ( \({r^}}\) = − 0.386, P = 0.140). Of note, HRs of PFS showed significant correlation with HRs of OS ( \({r^}}\) = 0.656, P = 0.015).

Conclusion

Elevated pretreatment blood NLR was a promising prognostic and predictive biomarker for advanced-stage cancer patients treated with immunotherapy.

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Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

Metastases are a major cause of complications and death among men with prostate cancer. Nearly all men who die from prostate cancer have antecedent metastases to bone or other sites, including the lymph nodes, lung, and liver. Bone metastases are associated with pain, pathologic fractures, and…

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Pathologic Staging of Endometrial Carcinomas: Selected Areas of Difficulty

Accurate staging of cancers is an important determinant of prognosis and guides optimal patient treatment. Although the International Collaboration on Cancer Reporting recommends that endometrial cancers (including carcinosarcomas) are pathologically staged using the International Federation of Gynecology and Obstetrics (FIGO) 2009 system, in many areas TNM [American Joint Committee on Cancer (AJCC) or Union for International Cancer Control (UICC)] staging is used or even mandated; these latter systems are based on FIGO 2009. In this review, areas of difficulty in the pathologic staging of endometrial carcinomas are covered with practical advice for the reporting pathologist. These include issues regarding the assessment of the depth of myometrial involvement (which may be rendered difficult due to a variety of factors), tumor involvement of adenomyosis, and assessment of cervical and uterine serosal involvement. Although not included in the FIGO staging system, the issue of lymphovascular space invasion (LVSI) is covered as this is of prognostic importance and there are multiple problems in the pathologic assessment of this. One important point is that tumors should not be upstaged based on the presence of LVSI alone without tissue involvement; for example, the presence of LVSI in the outer half of the myometrium or in cervical or adnexal vessels in a carcinoma with myoinvasion confined to the inner half of the myometrium is still FIGO stage IA. The issue of simultaneously occurring tumors of the endometrium and adnexa is also covered with advice on how to distinguish between synchronous independent and metastatic neoplasms of both endometrioid and nonendometrioid types. Recent molecular evidence showing that simultaneously occurring endometrioid carcinomas of the endometrium and ovary are clonal and thus probably represent metastatic disease from the endometrium to the ovary rather than synchronous independent neoplasms, as is widely assumed, is discussed.

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Disclosure of Harmful Medical Error to Patients: A Review With Recommendations for Pathologists

Harmful error is an infrequent but serious challenge in the pathology laboratory. Regulatory bodies and advocacy groups have mandated and encouraged disclosure of error to patients. Many pathologists are interested in participating in disclosure of harmful error but are ill-equipped to do so. This review of the literature with recommendations examines the current state of the patient safety movement and error disclosure as it pertains to pathology and provides a practical and explicit guide for pathologists for who, when, and how to disclose harmful pathology error to patients. The authors provide a definition of harmful pathology error, and the rationale and principles behind effective disclosure are discussed. The changing culture of medicine and its effect on pathology is examined including the trend towards increasing transparency and patient engagement. Related topics are addressed including the management of expected adverse events, barriers to disclosure, and additional resources for the implementation of disclosure programs in pathology.

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Hereditary Breast and Ovarian Cancer Syndrome: Moving Beyond BRCA1 and BRCA2

The recent implementation of next generation sequencing and multigene platforms has expanded the spectrum of hereditary breast and ovarian cancer syndrome, beyond the traditional genes BRCA1 and BRCA2. A large number of other moderate penetrance genes have now been uncovered, which also play critical roles in repairing double stranded DNA breaks through the homologous recombination pathway. This review discusses the landmark discoveries of BRCA1 and BRCA2, the homologous repair pathway and new genes discovered in hereditary breast and ovarian cancer syndrome, as well as their clinicopathologic significance and implications for genetic testing. It also highlights the new role of PARP inhibitors in the context of synthetic lethality and prophylactic surgical options.

http://ift.tt/2nNlEuf

Parasitic Infections of the Skin and Subcutaneous Tissues

A variety of arthropods, protozoa, and helminths infect the skin and subcutaneous tissues and may be identified by anatomic pathologists in standard cytology and histology preparations. The specific organisms seen vary greatly with the patient's exposure history, including travel to or residence in endemic countries. Arthropods are the most commonly encountered parasites in the skin and subcutaneous tissues and include Sarcoptes scabei, Demodex species, Tunga penetrans, and myiasis-causing fly larvae. Protozoal parasites such as Leishmania may also be common in some settings. Helminths are less often seen, and include round worms (eg, Dirofilaria spp.), tapeworms (eg, Taenia solium, Spirometra spp.), and flukes (eg, Schistosoma spp.). This review covers the epidemiologic and histopathologic features of common parasitic infections of the skin and subcutaneous tissues.

http://ift.tt/2nUxSQZ

Uterine Mesenchymal Tumors: Hereditary Aspects

The topic of hereditary gynecologic malignancies readily evokes associations between Lynch syndrome and endometrial adenocarcinoma, or between BRCA mutations and tubo-ovarian serous carcinoma, but other familial associations are less well-known. Two hereditary syndromes are known to be related to uterine mesenchymal tumors: hereditary leiomyomatosis and renal cell carcinoma syndrome and the tuberous sclerosis complex. In the following review, we describe the current literature on these syndromes, summarizing their clinical, morphologic, immunophenotypic, and genetic data. It is possible that the surgical pathologic diagnosis is the first indication of a familial syndrome, thus emphasizing the importance of a pathologist's familiarity with these potentially suggestive lesions.

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New Developments in the Molecular Mechanisms of Pancreatic Tumorigenesis

Pancreatic cancer is an aggressive disease with a dismal prognosis in dire need of novel diagnostic and therapeutic approaches. The past decade has witnessed an explosion of data on the genetic alterations that occur in pancreatic cancer, as comprehensive next-generation sequencing analyses have been performed on samples from large cohorts of patients. These studies have defined the genomic landscape of this disease and identified novel candidates whose mutations contribute to pancreatic tumorigenesis. They have also clarified the genetic alterations that underlie multistep tumorigenesis in precursor lesions and provided insights into clonal evolution in pancreatic neoplasia. In addition to these important insights into pancreatic cancer biology, these large scale genomic studies have also provided a foundation for the development of novel early detection strategies and targeted therapies. In this review, we discuss the results of these comprehensive sequencing studies of pancreatic neoplasms, with a particular focus on how their results will impact the clinical care of patients with pancreatic cancer.

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The dynamics of medical care in skin cancers

No abstract available

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Development of encorafenib for BRAF-mutated advanced melanoma

Purpose of review To describe the pharmacological properties, preclinical and clinical data of the novel V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF)-inhibitor encorafenib (LGX818) and to compare these with established BRAF-inhibitors in the treatment of locally advanced or metastatic melanoma. Recent findings Encorafenib has shown improved efficacy in the treatment of metastatic melanoma in comparison with vemurafenib. Combination with the MEK inhibitor (MEKi) binimetinib allows for higher dose intensities of encorafenib further improving response rates (RRs). Summary Combination therapy with BRAF and MEKi has evolved as a standard of care in the treatment of locally advanced or metastatic BRAFV600-mutated melanoma. Despite compelling initial RRs, development of treatment resistance eventually leads to tumor progression in the majority of BRAF/MEK-inhibitor treated patients. Moreover, treatment-related adverse events are frequent, resulting in a substantial proportion of dose modifications and/or treatment discontinuations. The second-generation BRAF inhibitor encorafenib has been developed aiming at improved efficacy and tolerability through modifications in pharmacological properties. Clinical phase 3 data show improved progression-free survival both for encorafenib monotherapy and combination therapy with binimetinib compared with vemurafenib. Overall survival data and regulatory approval of this novel substance are eagerly awaited.

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Molecular pathology of lung cancer: current status and perspectives

Purpose of review In this article, we summarize the current knowledge on molecular alterations in lung cancer that are targets for therapy, and provide an outlook on the future development of molecular pathology in precision oncology. Recent findings Lung cancer has become a paradigm for the success of molecular targeted therapies in solid tumors. Tyrosine kinase inhibitors are effective treatment options in adenocarcinoma patients with an EGFR, ALK, ROS1 or B-Raf Proto-Oncogene, Serine/Threonine kinase mutation. Additional molecular targets that are addressed in clinical trials include ERBB2, MET, RET, NTRK1 and FGFR. Therapies with antibodies that block the interaction of PD-L1 with PD-1 and thereby liberate an antitumor immune response have introduced a new era in cancer therapy with impressive therapeutic benefits. The high financial burden, treatment failures and therapeutic side effects of immunotherapies have prompted a search for biomarkers beyond PD-L1 expression, for example, tumor mutation load or immune cell profiling, that might more reliably identify patients that are likely to respond. Summary The discoveries of cancer research have been translated into the clinical management of lung cancer patients. So far, the approach of targeted therapy that is directed towards certain molecular alterations in a given tumor has been successful for adenocarcinomas, but not yet for squamous or small cell carcinomas. Further clinical progress will require a better understanding of the molecular interactions within cancer cells that will subsequently enable innovative drug designs. Diagnostic molecular pathology will be a provider of information on a tumor's features and thus, navigate precision cancer therapy.

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Medical bioinformatics in melanoma

Purpose of review Bioinformatic insights from next-generation sequencing has been integral in understanding melanoma biology, resistance to treatment and provided new avenues for melanoma treatment. Whole-genome sequencing, whole-exome sequencing and RNA sequencing has redefined the molecular classification of melanoma, revealed distinct genetic aberrations that define clinical subtypes of melanoma and uncovered the diverse heterogeneity that resides in an individual tumor. Recent findings In this review, we will summarize the recent whole-genome study that catalogs the genomic landscape across many melanoma subtypes, the single-cell RNA sequencing studies that interrogates tumor heterogeneity and the personalized vaccine approaches to melanoma treatment. Summary Whole-genome sequencing of diverse subtypes of melanoma revealed acral and mucosal subtypes to have a different genomic landscape compared with cutaneous melanoma. Acral and mucosal melanomas are characterized by low mutation burden and high structural variants. Single-cell RNA sequencing revealed high intratumoral heterogeneity and the existence of rare intrinsic drug-resistant populations. Lastly, vaccination against tumor neoantigens could be a potential personalized medicine therapy for melanoma patients. In summary, bioinformatics research is deeply ingrained in all aspects of melanoma research and will continue to blossom together for many years to come.

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Advanced PET imaging in oncology: status and developments with current and future relevance to lung cancer care

Purpose of review This review highlights the status and developments of PET imaging in oncology, with particular emphasis on lung cancer. We discuss the significance of PET for diagnosis, staging, decision-making, monitoring of treatment response, and drug development. The PET key advantage, the noninvasive assessment of functional and molecular tumor characteristics including tumor heterogeneity, as well as PET trends relevant to cancer care are exemplified. Recent findings Advances of PET and radiotracer technology are encouraging for multiple fields of oncological research and clinical application, including in-depth assessment of PET images by texture analysis (radiomics). Whole body PET imaging and novel PET tracers allow assessing characteristics of most types of cancer. However, only few PET tracers in addition to 18F-fluorodeoxyglucose have sufficiently been validated, approved, and are reimbursed for a limited number of indications. Therefore, validation and standardization of PET parameters including tracer dosage, image acquisition, post processing, and reading are required to expand PET imaging as clinically applicable approach. Summary Considering the potential of PET imaging for precision medicine and drug development in lung and other types of cancer, increasing efforts are warranted to standardize PET technology and to provide evidence for PET imaging as a guiding biomarker in nearly all areas of cancer treatment.

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Editorial introductions

No abstract available

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Treatment of ALK-positive nonsmall cell lung cancer: recent advances

Purpose of review The review will highlight recent advances in development of ALK-TKIs and management of patients with ALK-positive nonsmall cell lung cancer. Recent findings There has been rapid progress in the use of targeted therapies for ALK-positive NSCLC. Since the discovery, development and approval of crizotinib in 2011, three second-generation ALK-TKIs, ceritinib, alectinib and brigatinib have been approved by the FDA. A range of newer generation ALK inhibitors with improved potency against ALK and against mutations that confer resistance to crizotinib are in clinical development. Summary Our review will discuss the recent phase III data with ceritinib and alectinib as well as clinical trials with other ALK inhibitors. We will also address two important issues in the management of ALK-positive NSCLC, prevention and treatment of brain metastases and management of emergent ALK-TKI resistance mechanisms.

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