Embryo quality has long been considered the main determinant of implantation and pregnancy in IVF. Morphology – a visual assessment of an embryo’s shape and development – has since the very first days of IVF been the key to measuring this embryo quality, and only in recent years has this morphological grading been made somewhat more scientific with the introduction of time-lapse imaging. Yet the fact remains that many morphologically "good quality" embryos in IVF – between 30 and 60% in various studies – fail to implant in the uterus and make a pregnancy. What’s going wrong?
There is a strong case that chromosomal abnormalities in the embryo, which are not detectable by morphological assessment, carry some responsibility. Studies over several years have confirmed that the rate of chromosomal anomalies (aneuploidy) in embryos increases with patient age, which may explain a higher rate of implantation failure and miscarriage in older IVF patients. But even with embryo testing for chromosomal anomalies, embryos destined for transfer are still assessed morphological.
"The issue is that morphological grading by humans leads to wide inter- and intra-operator variation," said investigator Professor José Celso Rocha from São Paulo State University, Brazil. A study presented today at the 33rd Annual Meeting of ESHRE in Geneva will suggest that these long-standing difficulties may now be improved by using advances in artificial intelligence. Thus, mathematical variables derived from time-lapse images of embryo development may now be used such that an algorithm can classify images of an embryo’s development automatically – and so remove the human variable from the crucial task of morphological assessment. "To classify images automatically will increase the predictive value of our embryo assessment," said Professor Rocha. "By increasing objectivity and repeatability in embryo assessment, we can improve the accuracy of diagnosing embryo viability. Clinics can use this information as ‘artificial intelligence’ to customise treatment strategies and better predict a patient’s chance of pregnancy."
Behind the claims lies an analysis of images taken from the development of 482 seven-day-old bovine embryos, which were used to "train" the artificial intelligence system. This analysis identified 36 assessment variables, 24 of which formed the input of the artificial network architecture. It was notable that during this initial set-up phase only “serious errors” occurred in only 6% of the assessments. Overall, the artificial intelligence system had a 76% accuracy.
Moreover, says Professor Rocha, artificial intelligence demonstrated an improved inter-operator variation (embryologist accuracy score lower than the artificial intelligence score) and improved consistency and overall accuracy of results.
Professor Rocha notes that this work has now moved on to its early stages of development in human embryos, which is being carried out at the São Paulo State University (Dr Marcelo Nogueira) in collaboration with the Boston Place Clinic in London (Dr Cristina Hickman).
Professor Rocha described the main sources of error in morphological assessment by embryologists as their degree of professional experience, emotional stress, physical fatigue, and laboratory routine. "Those features will cause subjectivity in classification of the embryo," he said.
However, because the artificial intelligence system is a technique which analyses the embryo through mathematical variables, it offers low subjectivity and high repeatability, making embryo classification more consistent. "Nevertheless," said Professor Rocha, "the artificial intelligence system must be based on learning from a human being – that is, the experienced embryologists who set the standards of assessment to train the system."

The European Society of Human Reproduction and Embryology
www.eshre2017.eu/Media/ESHRE-2017-Press-releases/Hickman.aspx

“How long do I have, doctor?” For many cancer patients, following the initial shock of their diagnosis, thoughts quickly turn to estimating how much precious time they have left with family and friends or whether certain treatments could prolong their life.
While current methods of estimating mortality can be crude, patients with bowel cancer could soon more accurately predict their chances of survival, thanks to a new web calculator developed by academics at The University of Nottingham and medical software company ClinRisk Ltd.
The new tool, which can be accessed by doctors and patients alike, is intended to help people make more informed decisions around treatment and manage expectations following diagnosis.
Research to test the accuracy of the new calculator has shown that the tool can reliably predict both absolute survival rates for men and women with colorectal cancer.
The calculator also allows patients to update their mortality risk based on how long they have survived following a diagnosis of cancer.
The tool was developed by Professors Julia Hippisley-Cox and Carol Coupland in the University’s School of Medicine using the QResearch database, which gathers patient data from approximately 1500 general practices across England through EMIS Health’s clinical computer systems.
Professor Hippisley-Cox said: “Current methods of estimating survival tend to be unreliable and sometimes patients can be given a fairly misleading and unnecessarily gloomy prognosis based only on the grade and stage of their cancer, only to find that in reality they live much longer than these crude predictions when other information is taken into account.
“The good news is that this new calculator which doctors and patients can access will offer a far more realistic estimate. We understand that not everyone will want to do this, of course, but some patients are very keen on this approach so it’s an individual choice.”
Current methods of predicting survival are based on simple averages based only on age or the grade and stage of the cancer in the wider population.
The new tool looks at a range of additional risk factors including the patient’s, smoking history, body mass index, family history, other illnesses and treatments such as aspirin or statins as well as other information including whether they have had surgery or treatments such as chemotherapy to deliver a far more personalised prognosis.
The team used information from more than 44,000 patients from 947 practices to develop separate equations for men and women aged between 15 and 99 years old when diagnosed with bowel cancer.
They then tested the equations by using them retrospectively to predict the outcome at one year, five years and 10 years after diagnosis for 15,214 bowel cancer patients from 305 different GP practices and 437,821 colorectal cancer patients from the national cancer registry.
The results indicated that the team has devised strong models for the prediction of cancer survival outcomes.
They were also able to provide conditional survival estimates which show how mortality risks change over time, which are particularly important among patients where the initial prognosis is poor due to late stage disease.

University of Nottingham
www.nottingham.ac.uk/news/pressreleases/2017/june/new-web-calculator-to-more-accurately-predict-bowel-cancer-survival.aspx

The range of options for medicating emergency patients intranasally has greatly expanded in recent years and can even be preferable for certain patients, including children, according to the results of a paper published online.

‘For patients who are combative or having seizures, intranasal administration of certain medications can be really helpful,’ said lead study author Megan Rech, PharmD, MS, BCPS, BCCP of Loyola University Medical Center in Maywood, Ill. ‘These formulations can be especially useful for children, as they are not as painful and frightening as using intravenous or intramuscular routes. This route can also be an effective option for treating opioid overdoses.’

Common medications that can be administered via an atomizer that sprays the surface of the nasal cavity include midazolam, fentanyl, naloxone, ketamine and dexmedetomidine.

Midazolam, administered intranasally, can tranquilize and sedate children who are undergoing numerous emergency procedures. It can also be used to treat seizures in both adults and children. Fentanyl, a synthetic opioid, can be administered to adults and children intranasally for pain relief. Naloxone administered intranasally can be a first-line therapy in suspected opioid overdoses where there is no intravenous access because it can be simply and rapidly administered by lay persons and out-of-hospital personnel. Ketamine, an analgesic, can be administered intranasally for adults and children who have orthopaedic injuries or who are undergoing nasogastric tube placement. Intranasal dexmedetomidine works well to sedate and relieve pain for surgical and dental procedures in children.

‘Administering medications intranasally in the pre-hospital or emergency setting can be easy, fast and non-invasive,’ said Dr. Rech. ‘It is a welcome option for emergency physicians treating a wide variety of patients, sometimes in difficult situations.’

American College of Emergency Physiciansnewsroom.acep.org/news_releases?item=122826

Administration of the amino acid D-serine, a dietary supplement, contributes to the improvement of the cognitive and motor capacity of a patient with a mutation that affects glutamate receptors
A translational, multicenter study carried out by research groups of the Bellvitge Biomedical Research Institute (IDIBELL), San Juan de Dios Hospital (HSJD), the University of Barcelona (UB), Clinic Hospital (IDIBAPS), the University of Vic (UVic), Santa Creu i Sant Pau Hospital (IIB Sant Pau) and the thematic area of Rare Diseases (CIBERER), has unveiled the potential of D-serine – a dietary supplement – to improve the neuronal function of a patient with a mutation of the glutamate receptors associated to atypical Rett syndrome with severe encephalopathy. This collaborative study, led by Dr. Xavier Altafaj (Neuropharmacology Unit, IDIBELL), opens a new range of therapeutic options for patients with mutations that affect glutamatergic neurotransmission. Likewise, this study has allowed to establish a unique and novel experimental approach that is currently being transferred to an ambitious project that aims to design predictive algorithms that lead to personalized treatments that can be quickly transferred to the clinical practice for other mutations that affect glutamatergic transmission.
"The story begins about three years ago, when Dr. Ángeles García-Cazorla, a neuropediatrician at San Juan de Dios Hospital and professor at the University of Barcelona, contacted us regarding one of his patients, who presented an atypical form of Rett syndrome with severe encephalopathy”, explains Dr. Xavier Altafaj, leader of the study and member of the Neuropharmacology Unit IDIBELL-UB, led by Dr. Francisco Ciruela. While assessing the exome of this patient,  the geneticists of San Juan de Dios (Dr. Judith Armstrong) identified a mutation that affects the coding gene for a subunit of glutamate receptors of the NMDA type. "Our research group is specialized in the study of these type of receptors, which in physiological conditions are associated with learning processes, memory, neurodevelopment and neuronal plasticity, and which are the main actors in excitatory transmission and neuronal function”, Altafaj adds.
The HSJD medical team and Dr. Altafaj’s group were interested in finding out whether the patient’s mutation could be responsible for for her disability to some extent. To do so, the team of Dr. David Soto (UB-IDIBAPS) carried out several functional studies that allowed them to prove that the mutation drastically reduces the activity of the glutamate channel. With these results, the group of Dr. Altafaj started a second battery of cellular, physiological and biochemical studies with the participation of Dr. Carles Sindreu (UB), Dr. Àlex Bayés (IIB Sant Pau) and Dr. Francisco Ciruela (IDIBELL-UB), to characterize the consequences of the loss of function of mutated receptors.
At the same time, computational studies conducted by Dr. Mireia Olivella (UVic) revealed that the mutation of the glutamate receptor sequence – potentially responsible for the patient’s symptoms – modified the receptor structure, decreasing the size of the canal’s pore and thus its affinity for glutamate, as it was subsequently validated at the experimental level. Glutamate is the main excitatory neurotransmitter of the central nervous system; Consequently, if the channel activity of this receptor is impaired, calcium intake could be reduced, leading to a clear decrease in neuronal function.
"Bearing everything in mind, we had two options," says Dr. Altafaj: "either we spent years designing a personalized drug or therapeutic approach to specifically correct the hypophysiologicality of the affected receptors, or we looked for an existing drug or compound able to increase the functionality of these receptors, forcing their activity and improving calcium intake. We were faced with a time-dependent situation, since neurodevelopmental processes are critical at the patient’s age, and consequently we went for the second option."
In order to be activated, NMDA receptors require the simultaneous presence of glutamate and the amino acids glycine or serine, which act as co-agonists. Knowing that glycine also acts on other types of receptors, IDIBELL researchers proposed to administer D-serine – an already commercialized dietary supplement, easy to administer and without side effects – to improve receptor activation and rebound glutamatergic transmission. In vitro studies in cell lines and primary cultures showed that D-serine supplementation enhanced the activity of mutated receptors. These results led Dr. Ángeles García-Cazorla, with the consent of the patient’s parents, to start a D-serine supplemented diet.
Follow-up of the patient by the Drs. Ángeles García-Cazorla and Anna López (HSJD showed that dietary supplementation with D-serine can be associated with significant improvements in the patient’s symptoms, both at a motor and cognitive level. "The patient is able to develop basic motor tasks that were unthinkable of at the beginning of the treatment, 17 months ago. We could say that the patient is connected to the outside world that surrounds her, and this represents a critical and unavoidable step towards establishing new neuronal connections", Dr. Altafaj describes.
The researchers are cautious but optimistic at the same time: "the results that we observe in the patient after a year and a half are very promising and we hope that she continues to improve, but we must also bear in mind that they are the consequence of a combined effort of several therapeutic interventions. In addition to treatment with D-serine, neuro-stimulation therapies have also been implemented and parents have been able to create a very positive development environment that is also contributing. However, prior experience with similar clinical cases had not shown improvements that significant, and in this sense this study makes us feel very optimistic and encourages us to keep following this direction. "

Bellvitge Biomedical Research Institute (IDIBELL),
www.idibell.cat/modul/news/en/1007/a-personalized-treatment-with-metabolic-therapy-improves-the-motor-and-communication-skills-of-a-patient-with-atypical-rett-syndrome
 

In the first such collaboration of its kind, an expert panel of rheumatologists and orthopaedic surgeons has developed guidelines for the perioperative management of anti-rheumatic medication in patients undergoing total hip or knee replacement.
"Patients with rheumatic diseases who have joint replacement surgery are at increased risk for joint infection, a potentially devastating complication," said Susan Goodman, MD, co-principal investigator and a rheumatologist at Hospital for Special Surgery in New York City. "As infection risk is linked to the use of anti-rheumatic medication, our goal was to develop recommendations on when to stop medication prior to joint replacement and the optimal time for patients to restart treatment after surgery. Appropriate medication management in the perioperative period may provide an important opportunity to lower the risk of an infection or other adverse outcome."
The expert panel consisted of 31 specialists from more than 20 hospitals and professional organizations. The medication guidelines concern adults with rheumatoid arthritis; spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis; juvenile idiopathic arthritis; and lupus undergoing hip or knee replacement.
The study included traditional disease-modifying anti-rheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids. The panel developed guidelines on when to continue, when to withhold, and when to restart these medications, as well as the optimal perioperative dosing of corticosteroids.
Among the main recommendations:

• Non-biologic DMARDs may be continued throughout the perioperative period in patients with rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis and lupus undergoing elective hip or knee replacement.
• Biologic medications should be withheld as close to one dosing cycle as scheduling permits prior to elective hip or knee replacement and restarted after evidence of wound healing, typically 14 days, for all patients with rheumatic diseases.

The patient panel, which had significant input, attached far greater importance to preventing infection at the time of surgery than to the possibility of a disease flare from stopping medication.
"The recommendations are intended for use by clinicians, including orthopaedists, rheumatologists, and other physicians performing risk assessment and evaluation, as well as by patients," Dr. Goodman noted. "Communication is key. It is imperative that open and informed communication between the patient, orthopaedic surgeon and rheumatologist take place."

Hospital for Special Surgery
www.hss.edu/newsroom_expert-panel-rheumatologists-press-release.asp