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.