The timeline of Acetylsalicylic Acid
Aspirin (Acetylsalicylic Acid), who started its life as an ordinary headache tablet turned out to be an effective blood thinner and established itself on the cardiology shelves of our pharmacies. If the outcome of recent studies is to be confirmed, Acetylsalicylic Acid will soon be prescribed by oncologists.
Evidence is accumulating that Aspirin has a beneficial effect in the prevention of colorectal cancer. Some hypothesis suggests that Aspirin might play a role in the T cell-mediated anti-tumour activity.
While some public health organisations have started to give out recommendations to use this drug as preventative measures, there is still no consensus on how to involve this drug in a context with colorectal cancer.
Questions that need to be addressed:
- Should it be used as a primary or secondary prevention?
- Which age group should be targeted?
- Which risk group will benefit the most?
About 5% of patients with colorectal cancer have a rare genotype that does not respond to Acetylsalicylic Acid, in fact, these patients have an increased risk of developing CRC when using Aspirin. Should each patient be checked for this rare genotype before a recommendation can be made?
What will the future bring?
I believe that the near future and further studies will provide some answers soon. In the meantime, I remain in awe of that little headache pill and how new benefits of Aspirin are still being discovered today. The notion of Aspirin as a wonder drug is becoming more than an advertising slogan.
There is a new light shining into the corner of treatment-resistant depression: in the form of a drug called Ketamine. This substance, not new to the medical world, is thought to have a rapid effect in clinical depression and could become a life-saver for people with severe suicidal depression.
The drug has hallucinogenic and pain relieving properties and is well known to anaesthetists for its use during the general anaesthetic. Commonly known as “horse tranquillizer”, due to its use in veterinary medicine, it is also a Saturday night drug for clubbers who appreciate the ‘out of body experience’ in its recreational use. Ketamine act on a receptor in the brain called NMDA. The exact mechanism of action related to major depressive disorder is not known yet. Although the effect of Ketamine kicks in much faster than conventional antidepressants, which take up to 3 weeks to show a mood enhancement, initial doses fade quickly and a regular treatment plan is needed to gain a long-term effect.
A substance called Esketamine, in the form of a nasal spray is currently going through phase III clinical trials and, if all goes well, could soon become a reality and a possible alternative to last resort Electroconvulsive therapy (ECT). Provided that side effects and long-term risks are causing any concerns, we could at long last be able to have an effective first aid treatment for major depression that acts safely and quickly.
According to recent news China is reporting that it intends to accelerate the approval process for new medication by accepting the data from international clinical trials. This is obviously great news for many patients in need of new generation drugs such as immunotherapy.
By adopting this more open approach, the world’s second-largest drug market is providing exciting news to the international Pharma industry. In the long run, however, this move will reassure the steady drive of many R&D departments around the world and be a springboard for China to become a serious player in the development of new medication.
To give or not to give Oxygen
In case of an emergency and if in any doubt, give the patient oxygen. This first aid manoeuvre is also part of a knee-jerk when attending to an acute cerebrovascular accident. To protect brain tissue from hypoxia with continuous oxygen during the acute phase of a cerebrovascular accident seems to be a good idea. That was the motivation behind the SOS study in the UK, an extensive randomised control study conducted in acute stroke units all over the country for ten years. Most doctors who worked on an acute stroke unit over the last 10 years probably remember this study which managed to recruit over 8000 patients.
The Outcomes of the SOS study
The results are out and show that there is no benefit in giving every stroke patient routine low dose Oxygen (2 to 3 L/min), either continuously or at night time, in the first few days after the event.
A similar outcome was recently seen in a large US study, where benefits of routine oxygen administration in patients with an acute myocardial infarct failed to materialise.
Providing that oxygen saturations are continuously monitored, less routine Oxygen during an acute event can only be a good thing. For the simple reason that it will alert healthcare workers of an occurring acute hypoxia more quickly and could provide life-saving time for diagnosis and treatment thereof.
After encouraging results in treating melanoma, lung and kidney, immunotherapy enters the realm of gastric malignancies.
The FDA has approved Pembrolizumab, (Keytruda) by Merk, for use as a third-line treatment for locally advanced or metastatic adenocarcinoma of the stomach and gastro-oesophageal junction that express programmed death receptor-ligand 1 (PD-L1).
Immunotherapy tries to elicit the mechanisms how cancer cells can hide from the immune system. It aims to help our immune system in recognising a tumour and facilitating the natural immune response that is believed to be more efficient than any drug could ever be.
What is PD-L1
PD-L1 is a molecule that can be found on cancer cells, it binds with PD-1, a receptor present on T cells and therefore plays a role in immune regulation. When the two molecules bind they transmit an inhibitory signal that reduces the proliferation of T cells or even causes their death; in other words, PD-L1 tells the immune system not to bother attacking it.
How does Pembrolizumab work?
The concept of PD-L1 inhibitors is to block this molecule and thus prevent it from binding to the T cells. In other words, blocking the inhibitory effect in order achieve activation of the immune response.
The results so far
Taking into account that this is treating a third-line gastric cancer, the figures for 6- and 12-month duration of response are not mind blowing but show some promising features. Larger numbers will help to get a clearer picture in the future.
Immunotherapy in solid tumours is always going to be harder to achieve, especially in the advanced stages. It will be interesting to see what results can be reached when using PD-L1 inhibitors in combination with other treatments and also how it will fare as an early treatment.
Abbvie is coming up with some encouraging news from their phase III study evaluating the efficacy and safety of Venetoclax in combination with Mabthera/Rituxan compared to Bendamustine
Venetoclax or in brand name terms: Venclexta in the USA and Venclyxto in Europe, is an oral treatment consisting of a small molecule that, highly selectively, inhibits the BCL-2 protein.
The treatment is designed for patients who suffer from chronic lymphocytic leukaemia (the most common form of Leukaemia) having a specific chromosomal abnormality also known as the 17p depletion and who are not responding to the current treatment.
BCL-2 is part of a family of regulatory proteins involved in the regulation of programmed cell death (Apoptosis), either by inducing pro-apoptotic mechanism or inhibiting anti-apoptotic processes in the cell. BCL-2, in particular, is considered an important anti-apoptotic protein.
Some encouraging news for patients with CLL, will it do what Imatinib did for CML ?- time will tell!
WHO calls for prevention of the life-threatening condition, especially for maternal and neonatal sepsis:
12 September 2017:
Still today, Sepsis presents as a life-threatening condition. It can arise when the body’s response to infection causes injury to its tissues and organs. Infections often complicate underlying diseases; sepsis is a final common pathway leading to death from communicable or non-communicable diseases. If sepsis develops during pregnancy, during or after giving birth, or in context of abortion, we speak of maternal sepsis. Sepsis in a newborn baby is called neonatal sepsis.