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Dr. R. Srinivas, President Dr.C.N. Srinivas, Secretary & correspondent

Edited By Dr.S.Vidyadhara, Principal

Editorial Team: Dr. R. Hari Babu, Dr. R.L.C. Sasidhar,

S. Vikas, Dr. M.Raghava Kalyan

Testicular cancer-associated paraneoplastic encephalitis is a disease causing severe neurological symptoms in men. They progressively lose control of their limbs, eye movements, and, in some cases, speech. The disease begins with a testicular tumor, which appears to cause the immune system to attack the brain. Affected men often find themselves misdiagnosed or undiagnosed and appropriate treatment is delayed.The scientists identified a highly specific and unique biomarker for the disease by using a variation of "programmable phage display" technology. Their refined version of this technology simultaneously screens more than 700,000 autoantibody targets across all human proteins.

Using this powerful tool, the researchers evaluated cerebrospinal fluid from a 37-year-old man who had a history of testicular cancer and debilitating neurological symptoms, including vertigo, imbalance and slurred speech. The enhanced phage technology identified autoantibodies targeting Kelch-like protein 11 (KLHL11), which is found in the testes and parts of the brain.In addition to identifying the cause of this mysterious neurological disease, the results point the way to using this protein biomarker as a diagnostic test for men with testicular cancer-associated paraneoplastic encephalitis.

From darkroom to discovery

About 20 years ago, it was first identified a staining pattern that

NEWLY DISCOVERED AUTOIMMUNE DISEASE ASSOCIATED WITH TESTICULAR CANCER

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CHIPSCHIPSREGIMEN

Drug Information News Letter Jul-Sep 2019 Volume 5, Issue 1

Drug Information News Letter Jul-Sep 2019, Volume 5, Issue 1

✪ CHIPS ✪

FROM CONCEPT TO CREATION

✪ GUNTUR ✪

researchers dubbed "sparkles" because, in a darkroom under a microscope, the patient's sample looked like stars shining dimly in the night sky. The male patient had ataxia -- poor coordination, involuntary eye movements, change in speech -- and turned out to have testicular cancer.

Over the years, it was occasionally identified the sparkles pattern, and the patients' clinical stories were the same: ataxia and testicular cancer. But the pattern was faint and easy to miss, and an autoantibody target remained elusive.A team of researchers developed a customized version of phage technology that identified KLHL11 as the target for testicular cancer-associated paraneoplastic encephalitis based on a patient's sample. Physicians who suspect a patient may have this form of paraneoplastic encephalitis currently can screen for KLHL11. "Early diagnosis is extremely important," If we diagnose patients early, we can start them on immunosuppressive medications. The sooner we can prevent this damage from happening, the sooner we can stop the disease progression and the better chance we have for clinical improvement in the patient's life."In an epidemiological assessment, the prevalence of KLHL11 encephalitis was nearly 3 per 100,000 men. Thus, KLHL11 is one of the more common autoimmune encephalitis biomarkers found in in the U.S. and beyond.

Reference:

• Caleigh Mandel-Brehm, DivyanshuDubey, Thomas J. Kryzer, Brian D. O’Donovan, Baouyen Tran, Sara E. Vazquez, Hannah A. Sample, Kelsey C. Zorn, Lillian M. Khan, Ian O. Bledsoe, Andrew McKeon, Samuel J. Pleasure, Vanda A. Lennon, Joseph L. DeRisi, Michael R. Wilson, Sean J. Pittock. Kelch-like Protein 11 Antibodies in Seminoma-Associated Paraneoplastic Encephalitis. New England Journal of Medicine, 2019; 381 (1): 47 DOI: 10.1056/NEJMoa1816721

AI could enable accurate, inexpensive screening for atrial fibrillation

Artificial intelligence (AI) can detect the signs of an irregular heart rhythm — atrial fibrillation (AF) — in an EKG, even if the heart is in normal rhythm at the time of a test. In other words, the AI-enabled EKG can detect recent atrial fibrillation that occurred without symptoms or that is impending, potentially improving treatment options. This research could improve the efficiency of the EKG, a noninvasive and widely available method of heart disease screening. The findings and an accompanying commentary are published in The Lancet.

While common, atrial fibrillation often is fleeting. Therefore, it is challenging to diagnose. Atrial fibrillation may not occur during a standard 10-second, 12-lead EKG, and people are often unaware of its presence. Prolonged monitoring methods, such as a loop recorder, require a procedure and are expensive.

Accuracy and timeliness are important in making an atrial fibrillation diagnosis. Left undetected, atrial fibrillation can cause stroke, heart failure and other cardiovascular disease. Knowing that a patient has atrial fibrillation helps direct treatment with blood thinners.

"Blood thinners are very effective for preventing another stroke in people with AF. But for those without AF, using blood thinners increases the risk of bleeding without

TODAYS WATCHTODAYS WATCH

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STUDENTS CORNERSTUDENTS CORNERSGLT2 inhibitors – Updated advice on monitoring ketone bodies in patients hospitalised for major surgical procedures or acute serious medical illnesses

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has concluded its review of the risk of diabetic ketoacidosis (DKA) associated with sodium-glucose co-transporter 2 (SGLT2) inhibitors* in patients undergoing surgical procedures. SGLT2 inhibitors are indicated in adults for the treatment of Type 2 diabetes, as monotherapy or in combination with other diabetes medicines. In 2016, following a review of the safety data

substantial benefit. That's important knowledge. We want to know if a patient has AF."

Using approximately 450,000 EKGs of the over 7 million EKGs in the Clinic digital data vault, researchers trained AI to identify subtle differences in a normal EKG that would indicate changes in heart structure caused by atrial fibrillation. These changes are not detectable without the use of AI.

Researchers then tested the AI on normal-rhythm EKGs from a group of 36,280 patients, of whom 3,051 were known to have atrial fibrillation. The AI-enabled EKG correctly identified the subtle patterns of atrial fibrillation with 90% accuracy.

AI-guided EKGs could direct the right treatment for disease caused by atrial fibrillation, even without symptoms. Moreover, this technology can be processed using a smartphone or watch, making it readily available on a large scale.

available at the time, the PRAC considered that a small excess risk of DKA associated with SGLT2 inhibitors could not be excluded and that DKA with an atypical presentation may occur. The product information for SGLT2 inhibitors was updated thereafter to reflect this information and advise healthcare professionals that treatment with SGLT2 inhibitors should be interrupted in patients who are hospitalised for major surgery or acute serious illnesses due to the risk of DKA. In early 2019, newly identified cases of DKA associated with SGLT2 inhibitors occurring in patients undergoing surgical procedures prompted further evaluation of the associated risk factors. Following an in-depth review

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STUDENTS CORNERSTUDENTS CORNER

CLINICAL CONNECTIONCLINICAL CONNECTIONIRON DEFICIENCY IN PREGNANCY

Iron deficiency and the anaemia it causes are very common in pregnancy. The prevalence of anaemia during pregnancy is estimated to be around 25% with even higher rates in several countries. At the mild stage many of the clinical symptoms such as fatigue mimic the normal symptoms of pregnancy, making it difficult to identify. The consequences of untreated iron deficiency anaemia (IDA) can be quite severe for both mother and baby. IDA has been associated with multiple maternal conditions such as difficulty in fighting infection, an increased rate of postpartum haemorrhage and increased risk of postnatal depression. Risks for the baby include increased risk of pre-term birth, increased risk of low birth weight and also developing anaemia as a neonate. There are now many options for treating IDA. The first step is early detection and diagnosis. Checking the full blood count (FBC) at the first visit and again at 28 weeks. If anaemia is identified it is important to differentiate other causes and confirm an iron deficiency with ferritin levels. The current guidelines don’t recommend routine iron supplementation so an argument could be made for checking ferritin levels with the booking bloods to establish a baseline. Women identified with low ferritin could benefit from early intervention prior to developing anaemia. Good dietary advice at the hospital visit is also helpful to ensure an iron rich diet and also identify women at risk of deficiency due to dietary restrictions (i.e. vegetarians). A growing area of new challenges is women with potential absorption impairments, such as those whom have undergone gastric sleeve procedures. Once it is established that iron supplementation is required one of the most important steps is advising on an appropriate type and method of administration. Many patients will pick an iron supplement with an associated low side effect profile.

Unfortunately, these supplements achieve this by lowering the iron dose and causing a sub-therapeutic effect. Patients either don’t wish to take oral tablets, have poor absorption or cannot tolerate oral medication. New intravenous iron products have made infusion and supplementation much safer and easier to perform. They have revolutionised management of IDA in pregnancy. In previous years iron infusion was quite time consuming and this, coupled with a risk of anaphylaxis, led to a reliance on oral supplementation. This caused very unsatisfactory outcomes due to poor compliance with treatment, leading to anaemia at delivery. With the advent of ferric carboxymaltose with its low anaphylaxis rate and fast infusion rate, we are reversing this trend rapidly. If a patient fails a trial of oral supplementation after the first trimester we can quickly move to IV iron. This not only improves her symptoms making the pregnancy a much better experience, but likely improves delivery outcomes.

Reference : Frayne J, Pinchon D, Anaemia in pregnancy. AJGP 2019;48:3

of the available safety data, PRAC recommended that the SGLT2 inhibitors be updated to include a recommendation on how to assess for ketoacidosis in patients who are hospitalised for major surgical procedures or acute serious medical illnesses. The updated warning recommends that ketones be monitored following interruption of SGLT2 inhibitor treatment in these patients. Treatment may be

restarted when ketone values are normal and the patient’s condition has stabilised. There is evidence that SGLT2 inhibitors may diminish the excretion of ketone bodies in the urine, thereby making urine measurement of ketone bodies less reliable compared to blood testing. Therefore, measurement of blood ketone levels is preferred to urine.

1. Dr. V.Venkata Rao, Dr. Suryadevara Vidhyadhara. Development and Validation of Bioanalytical Method for the Quantitative Estimation of Selexipag In Biological Matrices using LC-MS/ MS. Journal of Pharmaceutical Sciences and research

2. Dr. Venkatarao V, B. Kusuma Sowjanya, D. Tejaswini1, E. Indumathi, J. Hari Sreekanth, T. Dileepkumar and Dr. S Vidyadhara. Protein Precipitant Activity of Ocimum Basilicum. International Journal of Pharmacy and Biological Sciences.

3. Viswanadh K, Vidyadhara S, Devala Rao G, Venkata Basaveswara Rao M, RLC Sasidhar. Solubility and Dissolution rate Enhancement of Ezetimibe by Solid Dispersion and Pelletization Techniques Using Soluplus as Carrier. International Journal of Applied Pharmaceutics.

4. Venkata Rao Vutla, Bhadru Banothu and Vidyadhara Suryadevara. Analytical Method Development and Validation of Pyrimethamine and Sulphadoxine in Pharmaceutical Dosage Forms by RP-HPLC. International Journal of Pharmacy and Biological Sciences.

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