How to measure the response to PGE-1 in non-reconstructable Peripheral arterial disease

In Non-reconstructable, leg peripheral arterial disease, the peripheral pulses at the ankle are generally not palpable and some times even doppler signals are not audible. Then it becomes a dilemma! in our minds about the assessment methods to measure of the response to treatment with Injections of PGE-1. We follow these patients based on the improvement of clinical symptoms such as pain, ulcer healing, 6 minute walking test, increase in the ankle pressures with portable doppler machine, intensity of the audible sound from the Dorsalis Pedis, Posterior tibial arteries. The ankle pressure may not improve immediately,  but slow and steady progress in the relief of symptoms is considered as positive response to the medication. The rest pain is relieved in majority of the patients. ulcers start healing in 6 weeks to 3 months. Mean while we should ask patients to refrain from smoking.

Prostaglandin E₁ (PGE1), also known as alprostadil, is a naturally occurring prostaglandin which is used as a medication.^[1] In infants with congenital heart defects, it is delivered by slow injection into a vein to open the ductus arteriosus until surgery can be carried out.^[2] By injection into the penis or placement in the urethra, it is used to treat erectile dysfunction.^[3] Common side effects when given to babies include decreased breathing, fever, and low blood pressure.^[1] When used for erectile dysfunction side effects may include penile pain, bleeding at the site of injection, and prolonged erection (priapism).^[1] Prostaglandin E₁ is in the vasodilator family of medications.^[1] It works by opening blood vessels and relaxing smooth muscle.^[1] Prostaglandin E₁ was isolated in 1957 and approved for medical use in the United States in 1981.^[1][4] It is on the World Health Organization's List of Essential Medicines.^[5]

1.  "Alprostadil". The American Society of Health-System Pharmacists. Archived from the original on 16 January 2017. Retrieved 8 January 2017.
2. ^ Northern Neonatal Network (208). Neonatal Formulary: Drug Use in Pregnancy and the First Year of Life (5 ed.). John Wiley & Sons. p. 2010. ISBN 9780470750353. Archived from the original on 13 January 2017.
3. ^ British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 569. ISBN 9780857111562.
4. ^ Sneader, Walter (2005). Drug Discovery: A History. John Wiley & Sons. p. 185. ISBN 9780470015520. Archived from the original on 13 January 2017.
5. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.

FDA Warns People to Avoid Compounded Semaglutide Medicines!

Semaglutide ( GLP1ra) is promoted as antidiabetic and anti obesity drug. There is increasing demand for this drug in  America (USA) and many parts of the world. The trials found out the safety and efficacy of this drug.  It resulted in shortage of the drug Semaglutide. So, alternates molecules are made available, but this brings us to a situation where we are concerned about the safety and efficacy of such alternate molecules which are not tested for their safety and effectiveness. So, FDA expressed its concern and given a warning and asked people to avoid using these molecules. It is more important to know for people buying the medications on-line to be cautious and aware of such directive from the FDA.

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https://www.medscape.com/viewarticle/992632?icd=login_success_email_match_norm

Can we use long PTFE graft for tibial bypass and limb salvage?

 

Generally, it is accepted that autogenous veins (GSVs) work better as Tibial artery bypass grafts. It could be due to the better compliance of the autogenous grafts with less intimal hyperplasia at the anastomotic junctions. Graft patency rate comes down as anastomosis goes down from the thigh to the ankle level. The photograph is showing the PTFE graft in the subcutaneous tissue and looks healthy. The surgeon feels happy to see such a result, but it is difficult to predict the future patency of the graft. Thrrombogenisity is high in such grafts, progressive vascular disease ( atherogenicity, intimal hyperplasia) make it difficult to predict patency.

Should IVC filters be retrieved or left behind?

 IVC filters are used to prevent pulmonary thromboembolism when the adequate anticoagulation is not effective, or contra indicated. There has been a tremendous growth in placement of retrievable IVC filters in the past decade, yet most of the devices are not removed. Unretrieved IVC filters have several well-known complications that increase in frequency as the filter dwell time increases. These complications include cava wall penetration, filter fracture or migration, cava thrombosis and an increased risk for lower extremity deep vein thrombosis (DVT). The risks of complex filter retrievals should be compared with those of life-long anticoagulation associated with an unretrieved filter and should be individualized. The removal of IVC filters requires specific skills and expertise.

• Daye D, Walker TG. Novel and Advanced Techniques for Complex IVC Filter Retrieval. Curr Treat Options Cardiovasc Med. 2017 Apr;19(4):28. doi: 10.1007/s11936-017-0529-3.

Are we threatened by Monkeypox?

 

 

    Figure: Monkeypox

What is monkeypox?

We are all petrified by the emergence of another new virus and we are curious to know its potential to cause another havoc and pandemic.

Monkeypox is caused by the monkeypox virus, which belongs to a subset of the Poxviridae family of viruses called Orthopoxvirus. This subset includes smallpox, vaccinia, and cowpox viruses. While an animal reservoir for the monkeypox virus is unknown, African rodents are suspected to play a part in transmission. Monkeypox was first discovered in 1958 when two outbreaks of a pox-like disease occurred in colonies of monkeys kept for research, hence the name 'monkeypox.' The first human case of monkeypox was recorded in 1970 in the Democratic Republic of Congo during a period of intensified effort to eliminate smallpox.

What does it cause?

It produces flu-like symptoms and also triggers enlargement of lymph nodes. Eventually, it produces distinctive fluid-filled lesions on the face, hands, and feet. Most people recover from monkeypox in a few weeks without treatment ( 4-5 weeks).

Monkeypox is related to smallpox or chickenpox?  It is more related to smallpox and the smallpox vaccine can provide protection to an extent of 85% from monkeypox.

Xenotransplantation

 Human organ donations such as kidney, liver, heart are saving the lives of the people with damaged organs. But there are not enough donors to meet the demand for organs.  The waiting lists are too long and many people are dying waiting for transplantation. How to over this hurdle? One of the way is to consider xeno-transplantation. Genetically modified pig is preferred for this organ transplantation. Kidneys from genetically modified pigs are transplanted in to the brain dead human beings and studied for 54 hours for acute rejection reaction, renal function improvement.  Dr . Richard Pierson, the scientific director for Transplantation science and a Professor of surgery at Harvard Medical School  gave an interview to Stephen Morrissey, Executive Managing Editor of NEJM.

The good side of it is, that we will be able to help needy patients. The negative side of it is that we are afraid of unknown viral injections jumping the species, like the AIDS virus. It was the reason for the initial refusal to consider the xeno-transplantations for some time. This can give rise to pandemics and we have to struggle to bring it down.

In this photo provided by the University of Maryland  School of Medicine, David Bennett Jr., right, stands next to his father’s hospital bed in Baltimore, Maryland on January 12, 2022, five days after doctors transplanted a pig heart into Bennett Sr., in a last-ditch effort to save his life. Bennett Sr., the first person to receive a heart transplant from a pig died on March 8, 2022, at the University of Maryland Medical Center, two months after the groundbreaking experiment. His death was announced on March 9, 2022. (University of Maryland School of Medicine via AP)

The Food and Drug Administration had allowed the dramatic Maryland experiment under “compassionate use” rules for emergency situations. Bennett’s doctors said he had heart failure and an irregular heartbeat, plus a history of not complying with medical instructions. He was deemed ineligible for a human heart transplant that requires strict use of immune-suppressing medicines, or the remaining alternative, an implanted heart pump.

 

Correlation of obesity & comorbid conditions with chronic venous insufficiency: Results of a single-centre study

 Indian J Med Res. 2018 May;147(5):471-476. doi: 10.4103/ijmr.IJMR_1844_16.Sandeep Mahapatra 1, Pinjala Ramakrishna 1, Bhumika Gupta 1, Arumalla Anusha 1, Muneer Ahmad Para 1

PMID: 30082571

 

PMCID: PMC6094506

DOI: 10.4103/ijmr.IJMR_1844_16

Free PMC article

Abstract

Background & objectives: Chronic venous insufficiency (CVI) is a common clinical problem among obese patients. This study was conducted to evaluate the impact of body mass index (BMI) and associated morbidities such as diabetes, hypertension and hypothyroidism on venous disease clinical scores as per Clinical, Etiological, Anatomical, Pathological (CEAP) classification. Methods: In this study, adult patients with BMI more than 30 kg/m2 with signs of CVI were evaluated clinically and by using Duplex ultrasonography of venous system. The patients with C0, C1, C2, C3 and C4, C5, C6 clinical scores in CEAP classification were grouped as lower and higher clinical scores of CVI, respectively. 

Results: Of the 200 enrolled patients, 147 (73.5%) were males and were associated with higher grades of clinical scores (P=0.051). Superficial venous system was involved in 96 per cent patients and 91 per cent patients had reflux in the sapheno-femoral junction. A negative association was observed between hypertension and male gender (P=0.001). Higher BMI was associated with higher clinical scoring (P=0.053). BMI >40 kg/m2 was associated with primary aetiology (P=0.007) of CVI. There was no correlation between superficial, deep or perforator incompetence with BMI (P=0.506). Duplex-confirmed significant reflux was observed in patients with higher BMI (P=0.006). Age and BMI were positively correlated with clinical score (r=0.176; P=0.013 & r=0.140; P=0.049), respectively. 

Interpretation & conclusions: Our findings indicated that elderly male patients with high BMI seemed to be at a higher risk of advanced clinical grades of CVI. The impact of comorbid conditions such as diabetes, hypertension and hypothyroidism on CVI could not reach at significance in the present study.

Stockings and venous disease

 Stockings and venous disease

Stocking as a part of compression therapy is the common prescription given to the patients attending the vascular (venous) clinics. Stockings are usually pressure graded. The maximum pressure is at the bottom level (ankle) and as we go up, the pressures decrease. These pressure graded compression garments are expected to improve venous flows and reduce venous stasis and ambulatory venous pressures. The venous symptoms are linked with ambulatory venous pressures (AVP). The higher (>80mmHg) AVPs are associated with non-healing venous ulcers.

Modern compression socks were invented by Conrad Jobst, a dashing German engineer who lived in Toledo, Ohio.  He suffered from varicose veins. The compression socks, which he invented around 1950, were his flagship achievement. They are tightest near the ankle, but still pretty tight up top. They work by countering hydrostatic pressure in the wearer’s legs. After Conrad's death in 1957, his wife, Carolyn Jobst, successfully grew the business. Under her leadership, JOBST^® expanded its product lines to include Ready-to-Wear vascular garments, consumer support stockings, plastic and reconstructive surgery garments, and anti-embolism stockings. Sales extended to virtually every continent as the JOBST reputation for quality grew. 

Renal transplantation in human and progression

Today, a patient with pulsatile aneurysm(6cm x 4cm x 5 cm) at the left wrist near the site of arteriovenous fistula was referred to me by the nephrologist for consideration of excision. It is a pulsatile swelling and there are no visible dilated veins to confirm the patency of the arteriovenous fistula. It was difficult to do the Allen's test as the vessels seam to be calcified. I suggested the possible treatment of excision of the aneurysm after confirming potency of ulnar artery which is provider of major arterial supply to the hand. But, did not appear to be satisfied with my suggestion. He said he is on long list of medications(14) including immunosuppressives., as the creatinine is raising (2.3 mg). He said after kidney transplantation in 2004 (donor was his sister-in-law) he had long tumultuous period. Two more operations were done. One was hip replacement, the second was eye operation. He is a beneficiary of railway health scheme. He is not ready for the operative correction of the AVF aneurysm at left wrist region. I consoled him and said 'let us do the colour doppler scan and decide about the line of management later on'. He asked me what would happen if we leave it like that? I told him slowly that it can develop thrombus, embolism, rupture, endanger circulation to the fingers and compress the neighbouring nerve fibers. I thought he might ask me the next question, about the life expectancy in his condition. But he did not ask. During last 17years, he might have seen many ups and downs in his life from various angles. I told him once again, we will take decision during the next visit after seeing the duplex scan report. The patient left the consultation room, nodding his head reluctantly, it appeared the interview was incomplete. I could sense that he wanted to ask me many more questions, for which probably I do not have perfect answers. I waited for a minute, stretched my legs, closed my eyes and thought over the progress we made in the renal transplantation services in the last 50 years in India. Though, we made significant improvements there seems to be lot more to be done. I want you to read the progress that took place in renal transplantation in the paragraph below.  

The history of kidney transplantation is a history of many unsuccessful efforts and setbacks, but also the history of perseverance, pioneering spirit, and steadfast courage. The first successful transplantation of a dog kidney was done by the Austrian Emerich Ullmann (1861-1937) in 1902. The kidney was connected to the carotid artery of the dog and the ureter ended freely. The organ produced urine for a couple of days before it died. In 1909, there were efforts to transplant human kidneys from deceased patients to monkeys and in the following year the first xenotransplantation in humans was completed. Different kinds of donors were tried: dogs, monkeys, goats and lambs, all without success. In 1939, the first transplantation from a deceased human donor was done by the Russion Yurii Voronoy, the patient survived for only a couple of days, and the organ never worked. In 1953, the first temporarily successful transplantation of a human kidney was performed by Jean Hamburger in Paris. A 16-year-old boy received the kidney of his mother as living donor transplantation. Then in 1954, a milestone was made with the first long-term successful kidney transplantation by Joseph Murray: the transplantation was done between monozygotic twins; the organ survived for 8 years. For his efforts in kidney transplantation, Murray was honored with the Nobel Prize in medicine in 1990. In 1962, the first kidney transplantation between genetically nonrelated patients was done using immunosuppression and in 1963 the first kidney transplantation in Germany was done by Reinhard Nagel and Wilhelm Brosig in Berlin. The aim of this article is to present the history of kidney transplantation from the beginning until today.

oral semaglutide

 

Oral semaglutide in type 2 diabetes

Sarah L Anderson 1, Trevor R Beutel 2, Jennifer M Trujillo 3

DOI: 10.1016/j.jdiacomp.2019.107520   

Background: Previously, the only available glucagon-like peptide-1 receptor agonists (GLP-1 RA) were injectable. Approval of oral semaglutide (Rybelsus®) represents the first orally available GLP-1 RA Objective: To review the literature and describe pharmacologic, pharmacokinetic, and pharmacodynamics properties; clinical safety; and efficacy of oral semaglutide, a newly approved oral GLP-1 RA. Methods: A MEDLINE (1995-October 2019) and ClinicalTrials.gov search was conducted using the terms oral semaglutide, semaglutide, PIONEER, and a combination of those terms. Reference citations from publications identified were also reviewed. All English-language studies, including abstracts, evaluating oral semaglutide use in humans were included in this review.

Conclusions: The approval of oral semaglutide (Rybelsus®) represents a paradigm shift in the management of T2D as this is the first FDA-approved oral GLP-1 RA. Oral semaglutide may be an attractive option for patients with T2D who require improved glycemic control, would like to lose weight, and who are not interested in injectable therapy. However, the lack of positive cardiovascular (CV) and renal data are significant limitations to its use.

Reinfection of Covid-19

 

The corona virus information is exploding in the media. Some are talking about 2^nd wave, others predicting the 3^rd wave of infection. They are comparing the Indian data with the other countries such as USA and European countries. We are also hearing about the infection after successful 2 dose vaccination and previous covid-19 infection. The common question is why they are getting the re-infection again after one infection or vaccination. It is also puzzling to see re-infection after getting adequate antibodies after vaccination and first infection. One consolation is that not many of them are requiring hospitalization, oxygen therapy and ventilation support. Vaccines are not cent percent protective. Virus mutation is one explanation, breech in the protection measures is the other explanation given by the experts for the rapid spread of 2^nd wave. In the first wave we did not hear that members in family circles got infected, but the in the second wave are hearing that someone known to us, close to us are got infected and in home quarantine. We are also and knowing about the deaths in families known to us. Both middle aged ( 18-45 years) and those above 60 years are in this list. RT PCR test is dependable for diagnosis of Covid-19, but it is negative initially in some of those with all the symptoms of Covid-19 disease. A repeat RT PCR test after 3-4 days is turning out to be positive. The CT(cycle threshold) values are ranging from 16 to 25. After 10 days are CT values are dropping and becoming normal. Few people are requiring advanced therapies and steroids. However there is crazy demand for Remdesivir, tocilizumab injections and some are arguing that it should be used early though there is no supportive evidence. The views are rapidly changing and the mad rush for oxygen therapy is getting stabilized.

Long-term efficacy and safety of drug-coated balloons versus drug-eluting stents for small coronary artery disease (BASKET-SMALL 2): 3-year follow-up trial

In the treatment of de-novo coronary small vessel disease, drug-coated balloons (DCBs) are non-inferior to drug-eluting stents (DESs) regarding clinical outcome up to 12 months, but data beyond 1 year is sparse. We aimed to test the long-term efficacy and safety of DCBs regarding clinical endpoints in an all-comer population undergoing percutaneous coronary intervention.

In this study, Between April 10, 2012, and Feb 1, 2017, of 883 patients assessed, 758 (86%) patients were randomly assigned to the DCB group (n=382) or the DES group (n=376). The Kaplan-Meier estimate of the rate of major adverse cardiac events was 15% in both the DCB and DES groups (hazard ratio [HR] 0·99, 95% CI 0·68–1·45; p=0·95). The two groups were also very similar concerning the single components of adverse cardiac events: cardiac death (Kaplan-Meier estimate 5% vs 4%, HR 1·29, 95% CI 0·63–2·66; p=0·49), non-fatal myocardial infarction (both Kaplan-Meier estimate 6%, HR 0·82, 95% CI 0·45–1·51; p=0·52), and TVR (both Kaplan-Meier estimate 9%, HR 0·95, 95% CI 0·58–1·56; p=0·83). Rates of all-cause death were very similar in DCB versus DES patients (both Kaplan-Meier estimate 8%, HR 1·05, 95% CI 0·62–1·77; p=0·87). Rates of probable or definite stent thrombosis (Kaplan-Meier estimate 1% vs 2%; HR 0·33, 95% CI 0·07–1·64; p=0·18) and major bleeding (Kaplan-Meier estimate 2% vs 4%, HR 0·43, 95% CI 0·17–1·13; p=0·088) were numerically lower in DCB versus DES, however without reaching significance.

Interpretation

There is maintained efficacy and safety of DCB versus DES in the treatment of de-novo coronary small vessel disease up to 3 years.

Does it mean there will be a shift towards to DCBs., less need for DES?

Did we understand the total picture of the COVID-19?

Did we understand the total picture of the COVID-19? Is there something more to unfold in the coming months?

Multisystem inflammatory syndrome in children (MIS-C) is a newly described condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure that is reminiscent of both Kawasaki disease and toxic shock syndrome. There is recent surge in this disease. It has prompted us to increase the awareness of MIS-C.  The number of reported cases continues to increase. Kawasaki-like multisystem inflammatory condition is a possibility in adults. The first case is reported in USA.

A constellation of signs 1)fever for more than 5 days, 2)erythema multiforme-like rash, 3)bilateral non-exudative conjunctivitis, 4)erythema or cracking of the lips, 5)unilateral cervical lymphadenopathy measuring more than 1·5 cm in diameter), the American Heart Association (AHA) criteria for Kawasaki disease were noted in a man. So, based on these criteria he was diagnosed with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19. It was notable that he did not experience the hypoxic respiratory failure most frequently associated with moderate to severe COVID-19, despite his abnormal chest x-ray findings. He exhibited many MIS-C-related features such as a predominance of gastrointestinal symptoms, generalised extremity pain, and prominent cardiac dysfunction, and his cardiac findings (elevated cardiac enzymes and left ventricular hypokinesis with a reduction in ejection fraction) resemble findings of myocarditis recently described in MIS-C. This patient's palmar lesions are distinct from the acral erythema and swelling with subsequent desquamation typically seen in Kawasaki disease, and his diffuse conjunctivitis was not limbic-sparing. Biochemically, he demonstrated markedly elevated C-reactive protein, neutrophilia, and lymphopenia, which are more consistent with MIS-C than with classic Kawasaki disease. Emerging reports depict the phenotype of MIS-C as a combination of Kawasaki disease, toxic shock syndrome, and macrophage activation syndrome (or haemophagocytic lymphohistiocytosis), these are all syndromes of dysregulated immune responses. Diagnostic distinction from classic Kawasaki disease might have meaningful implications: whereas treatments targeting IL-6 are currently being investigated among therapeutic options for COVID-19-associated hyperinflammation, the IL-6 inhibitor tocilizumab might provoke the development of coronary artery aneurysms in patients with classic Kawasaki disease. Though this is a rare presentation of one case in association with COVID19, we should be aware of such can be associated and we vigilant in the future.