Archive for month: August, 2020

For patients with colorectal cancer that has metastasised to the liver, having a primary tumour on the left side, as opposed to the right side of the colon, is known to be a significant advantage in terms of treatment response.
But now a new study, presented here at the ESMO 19th World Congress on Gastrointestinal Cancer, suggests this imbalance may be at least partially redressed.
Reversing the usual pattern, patients whose liver metastases had spread from right-sided primary tumours (RSP) had a 36% better survival rate after treatment with a combination of first-line chemotherapy and selective internal radiation therapy (SIRT) using Y-90 resin microspheres, compared to chemotherapy alone, according to the study.
This same treatment combination was no better than chemotherapy only in patients with left-sided primary tumours (LSP).
“These findings are good news for patients with right-sided primary tumours, who have a much worse prognosis and fewer treatment options than patients with left-sided tumours,” said study investigator Guy van Hazel, MD, from the University of Western Australia in Perth, Australia.
“We are excited because hitherto no treatment apart from the addition of bevacizumab to chemotherapy has improved the dismal outcome of liver metastases coming from right-sided primary tumours.”
The analysis included 739 patients from two completed studies called SIRFLOX (SF) and FOXFIRE-Global (FFG).
All patients had liver-only or liver-dominant metastatic colorectal cancer (mCRC), and had been randomised to receive either standard chemotherapy alone, or combined with SIRT. The chemotherapy regimen was mFOLFOX6, and most patients received bevacizumab as well.
Information on the patients’ primary tumour location was recorded at the start, with 24% having right-sided and 73% left-sided disease (the remaining 3% had primary tumours on both sides of the colon, or the primary tumour site was unknown).
Overall, outcomes were not different between the chemotherapy alone and chemotherapy plus SIRT groups, with median overall survival (OS) and progression-free survival (PFS) around 24 months and 11 months, respectively.
However, when the investigators examined patients with RSP and LSP separately they saw a clear difference.
Patients with liver metastases from RSP had significantly better OS when SIRT was added to their chemotherapy compared to those who had chemotherapy alone (22.0 vs. 17.1 months, respectively; p=0.007; Hazard Ratio [HR]: 0.64 [95% CI: 0.46-0.89]), but this was not the case for patients with LSP (24.6 vs. 25.6 months; p=0.279; HR: 1.12 [0.92-1.36]).
“That means that RSP patients treated with chemotherapy plus SIRT have a 36% reduced risk of dying at any time point,” said van Hazel.
There was also a 27% improvement in PFS, although this was not statistically significant.
“This is the first time that location of primary tumour has been linked to radiation therapy,” said van Hazel, and although it’s possible that it may only apply to patients receiving first-line therapy, he said it opens a new treatment option for these patients.

ESMO
www.esmo.org/Press-Office/Press-Releases/Right-sided-Colorectal-Tumours-An-Internal-Radiation-Advantage?hit=ehp

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
 

Common orthodontic problems such as crossbite, overbite, underbite, and crowding of the teeth can have a negative impact on a person’s physical appearance, dental function, and overall self esteem. To make a diagnosis and plan treatment, orthodontists currently take multiple x-ray images of the entire skull before, during and after orthodontic treatment. Part of the skull, the cranial base, is used as a stable reference for determining the position and orientation of the jaws and teeth when planning treatment changes. While the amount of radiation is small, x-rays of the whole skull taken multiple times during treatment can be a concern, especially for paediatric patients who are generally more susceptible to the harmful effects of ionizing radiation than adults.
A recent study suggests that another approach using non-radiographic 3-D dental photogrammetry could offer accurate dental and facial measurements based on using the eyes and natural head orientation as references rather than the cranial base.
Mohamed Masoud, director of Orthodontics in the Department of Developmental Biology at the Harvard School of Dental Medicine, along with his research team studied 180 females and 200 males between the ages of 18 and 35 using 3-D facial and dental imaging to produce an adult sample with near ideal occlusion and a pleasing facial appearance. The goal was to provide reference values that can aid practitioners in determining the relative position and orientation of a patient’s dental and facial structures without exposing the cranium to radiation.

Harvard University
news.harvard.edu/gazette/story/newsplus/new-research-suggests-3-d-photography-could-offer-better-orthodontic-diagnosis-using-less-radiation/

A new University of Alberta study showed that around-the-clock care from senior physicians helped reduce major complications in cardiac surgery patients as compared to receiving care from resident physicians. The study examined the results of more than 3,000 Alberta patients at the University of Alberta Hospital and Mazankowski Alberta Heart Institute.  Around-the-clock care from senior physicians helped reduce major complications in cardiac surgery patients as compared to receiving care from resident physicians, according to a new University of Alberta study.
Researchers found that patients who received 24/7 intensivist physician care had a seven per cent lower risk (26% vs 19%) of experiencing major complications and a nearly-four per cent lower chance (5.3% vs 1.6%) of cardiac surgical intensive care unit (ICU) readmission. Patients also experienced less time receiving mechanical ventilation and fewer surgical postponements.
The study examined the results of more than 3,000 Alberta patients at the University of Alberta Hospital and Mazankowski Alberta Heart Institute. Half were cared for at night by resident physicians over a seven-year period (2006-2013), with the other half cared for by dedicated in-house intensivist physicians over a period of 17 months (2013 and 2014).
“There have previously been large studies [examining this issue in general ICU units] and they have not found any benefit to taking residents away or adding staff physicians,” said study author Marc Benoit, a fellow in cardiology at the University of Alberta. “But we thought the cardiac ICU here might be different because the patients are more complex. Someone with a heart transplant who is sick is different than a standard hospital patient.”
“With more senior staff in-house at night, people were taken off the ventilators faster and we think there probably was more attention to detail for infection prevention. That is a possible explanation.”
Benoit stressed the findings were observational and that it cannot definitively be said that the change in staffing model was responsible for the outcomes. While the findings seem to support the use of senior physicians in specialized cardiac surgery ICUs, Benoit also notes that each hospital has unique circumstances and that careful thought needs to be put into the staffing of each of them.
“When looking at this issue of nighttime staffing, we need to consider the patient population. So maybe it’s not beneficial to keep senior physicians in-house in every single ICU, but it might be in some more complex units,” said Benoit.
“It is worth thinking about. Staffing patterns and care models can have very important effects on patient outcomes.”

University of Alberta
www.ualberta.ca/medicine/news/2017/july/improving-cardiac-icu-outcomes-through-specialized-24-7-care