Tag: 10/3/21

Categories : General Interest TransplantsTags :

Teen Embraces Chance to ‘Live Well’ With Kidney Disease

On By ModernMedia

Thanks to a young organ donor, Bronwen Fredericks has a new kidney that she and her mother Bridget are deeply thankful for.
The 15-year-old was one of two patients at Red Cross War Memorial Children’s Hospital who received their new kidneys last month. With a new chance at their childhoods, they have a chance to embrace the spirit of “Living Well with Kidney Disease”, the 2021 theme for World Kidney Day tomorrow. 

Bronwen said: “I’m really grateful to my donor and excited for my new life. I’m really looking forward to being able to dance again.”

According to her mother, a blood pressure test had alerted them to the problem.

“I would like to encourage everyone, especially parents, to do a regular general check-up with their children at a clinic or GP. A simple blood pressure test could show us that there was a serious problem and we were able to take action that saved my daughter,” she said.

“Irrespective of age, being diagnosed with kidney disease can pose a huge challenge for the patient and their family. It remains draining on those involved, be it emotional, financial, physical or a combination of these – but imagine the impact on a young child,” the Red Cross War Memorial Children’s Hospital said in a statement on Wednesday.  The hospital conducts around 10 to 12 kidney transplants a year.

The Red Cross Hospital said it is aiming to reduce stress factors through education, empowerment and by building a partnership with patients and their families.

“The diagnosis and management, particularly in the advanced stages of kidney disease, impacts severely upon the lives of our young patients by reducing their ability to participate in everyday activities like attending school, participating in extra-curricular activities and socialising, whilst the whole family’s ability to travel and parents ability to work is also affected,” said Dr Deveshni Reddy, ‎paediatric nephrologist at the hospital.

Current management includes dialysis to take the strain off of kidneys, and in more extreme cases, donor transplants.
Professor Mignon McCulloch, the hospital’s head of paediatric nephrology and solid organ transplantation, said: “While we always try our best to treat chronic kidney disease and other kidney disorders through medical intervention, sometimes a surgical intervention, or dialysis and resultant kidney transplant, is the only option.

“The Red Cross War Memorial Children’s Hospital conducts around 10-12 kidney transplants per year, making it one of the most active paediatric transplant services in South Africa, which is only possible due to the close collaboration with the multi-disciplinary role-players from Groote Schuur Hospital and Red Cross.”

Source: IOL News

Categories : CancerTags :

No Survival Benefit Seen for PD-1 Inhibitor in Triple-negative Breast Cancer

On By ModernMedia

Results of a large randomised trial showed no survival improvement in previously treated metastatic triple-negative breast cancer (TNBC) with single-agent pembrolizumab versus chemotherapy.

Eric Winer, MD, of Dana-Farber Cancer Institute in Boston, presented findings from his team’s randomised trial KEYNOTE-119, which compared pembrolizumab monotherapy versus single-agent chemotherapy as second or third-line therapy for metastatic TNBC. Investigators randomised 622 patients to the two treatment arms. The primary analysis in patients with a PD-L1 combined positive score (CPS) ≥10 showed a median overall survival (OS) of 12.7 months with pembrolizumab and 11.6 months with investigator’s choice of chemotherapy. No significant advantage for pembrolizumab was seen in analyses of patients with CPS ≥1 and the overall population. 

Pembrolizumab led to fewer grade 3/4 treatment-related adverse events (TRAEs). The most common grade 3/4 TRAEs all  more often with chemotherapy, with serious AEs occurring in 20% of each group.
After a median follow-up of 31 months, analysis of the CPS ≥10 subgroup showed the pembrolizumab arm had a non-significant 22% reduction in the survival hazard. The CPS ≥1 analysis yielded median OS values of 10.7 months for the pembrolizumab arm and 10.2 months for the chemotherapy arm. Analysis of the overall population showed a median OS of 9.9 months with pembrolizumab and 10.8 months with chemotherapy. There was some evidence from a post hoc exploratory analysis that pembrolizumab activity might increase with higher CPS values.

“These findings might inform future research of pembrolizumab monotherapy for selected subpopulations of patients, especially those with PD-L1-enriched tumours, and inform a combinatorial approach for the treatment of patients with metastatic triple-negative breast cancer,” the researchers concluded.

The findings are consistent with the history of single-arm anti-PD-1/L1 therapy for breast cancer, said Eitan Amir, MD, and David W Cescon, MD, PhD, both of Princess Margaret Cancer Center in Toronto. In all types of breast cancer, checkpoint inhibitors have produced low response rates, but this has been consistent.

“Given the low response rates observed in the overall population with pretreated triple-negative breast cancer in previous studies of anti-PD-1 or anti-PD-L1 monotherapy, the primary results of KEYNOTE-119 are unsurprising,” they wrote. “Since KEYNOTE-119 was launched, clinical development has focused principally on combinations of chemotherapy and immunotherapy in the first-line setting.”

Drs Amir and Ceson cautioned that the results of the post hoc analysis are intriguing but must be treated with caution.

“The finding that this higher PD-L1 expression threshold might be a predictor of pembrolizumab monotherapy benefit adds to previously observed associations with single-drug immunotherapy benefit, including de novo metastatic disease, absence of previous chemotherapy, normal lactate dehydrogenase, lung or nodal involvement, and absence of liver metastases […] . It would be intriguing to see if similar results can be validated in triple-negative breast cancer,” Amir and Cescon added.

Source: MedPage Today

Categories : COVID HospitalsTags :

Brazil’s Hospitals Are on The Brink of Collapse

On By ModernMedia

Health systems in most of Brazil’s largest cities are close to collapse because of COVID cases, its leading health institute Fiocruz warns.

More than 80% of intensive care unit beds are occupied in the capitals of 25 of Brazil’s 27 states, Fiocruz said.  The highly contagious variant that emerged in Brazil may have serious knock-on effects for the rest of the world, health experts have warned.

In a stark warning, Fiocruz epidemiologist Jesem Orellana told AFP news agency that  “Brazil is a threat to humanity.”

Brazil’s President Jair Bolsonaro had already provoked outrage among his citizens and rebukes from local leaders by telling people to “stop whining” about COVID. The country recorded 1972 COVID deaths on Tuesday, along with a surge to 70 000 cases — a 38% increase on last week’s figure. ICUs at 15 state capitals are at 90% capacity, said Fiocruz, and in two cities, Porto Alegre and Campo Grande, they had exceeded capacity.

“The fight against COVID was lost in 2020 and there is not the slightest chance of reversing this tragic circumstance in the first half of 2021,” Fiocruz’s Jesem Orellana said, as quoted by AFP.

“The best we can do is hope for the miracle of mass vaccination or a radical change in the management of the pandemic. Impunity in management seems to be the rule.”

Of the currently available vaccines, so far Pfizer’s has been confirmed to be effective in lab tests against a specially engineered version of the virus made to mimic the variant.

Source: BBC News

Categories : HIVTags :

Home Deliveries of Antiretrovirals Worked Better for SA HIV Patients

On By ModernMedia

A study investigating the feasibility of home delivery of antiretroviral therapy (ART) was well received and had significantly more participants achieving viral suppression.

In South Africa, 27% of the population is HIV positive, with viral suppression achieved only in 64% of the population. Post-apartheid healthcare reforms have done little to improve access to healthcare for most South Africans. HIV positive pregnant women, for example, have difficulty achieving viral suppression for a number of reasons including crowded clinics that are often at a great distance.

To investigate the feasibility of home delivery of ART recruited 162 people living with HIV, 88% of those randomised to home delivery experienced viral suppression (defined as viral loads less than 100 copies/ml) compared to 74% of those randomised to clinic visits, reported Ruanne Barnabas, MBChB, DPhil, of the University of Washington. The participants were followed for a median of 47 weeks, even during COVID restrictions.

Dr Barnabas reported that the difference was even more pronounced in men (64% in clinic group vs 84% in delivery group). This is important as there are gaps in viral suppression with standard, clinic-based ART, especially among men and priority populations. Home ART delivery and monitoring can increase access and the intention to treat.

“If a client pays for the service, and the benefits are sufficient, this could become a scalable strategy,” Dr Barnabas said. This could help achieve UNAIDS viral suppression targets for South Africa of 86%, she added.

Dr Barnabas described the home delivery as an Amazon Prime-type service, where clients paid an income-scaled one-time fee, for ART delivery and monitoring.

Viral load testing was a secondary objective while testing of the ability to pay the fee and the acceptability of the service was the primary objective. The participants were from a lower income group, with 19% being labourers or semi-skilled workers, and 60% unemployed.

The participants responded well to the home delivery, with 98% of participants paying the fee, and 100% saying they thought the fee was reasonable, that it reminded them to take their medications, and that they would continue to pay it if delivery was available. The next step would be to see if the service could be financially viable if scaled up. 

Source: MedPage Today

Presentation information: Barnabas R, et al “Fee for home delivery and monitoring of ART raises viral suppression in South Africa” CROI 2021; Abstract 111LB.

Categories : COVIDTags :

How The COVID Variant Was Discovered in South Africa

On By ModernMedia

The so-called South African variant was identified by an international team of researchers, including biomedical scientists from the University of California, Riverside. They explain the process behind discovering the variants, why they are so concerning, and what the future holds.

“The new COVID variants are the next new frontier,” said Adam Godzik, a professor of biomedical sciences in the UC Riverside School of Medicine. “Of these, the SA and Brazil strains are most worrying. They have mutations that make them resistant to antibodies we generate with existing vaccines. It is commonly believed we are in a tight race: Unless we vaccinate people quickly and squash the pandemic, new variants would dominate to the point that all our COVID vaccines would be ineffective.”

Prof Godzik and Arghavan Alisoltani-Dehkordi, a postdoctoral researcher who joined his lab two years ago, helped characterise the new SA variant by providing its spike protein structure using computer simulations.  

Dr Alisoltani-Dehkordi, who was a postdoctoral fellow at the University of Cape Town before she joined UCR, mentioned that research teams at the University of KwaZulu-Natal  and UCT discovered the new SARS-CoV-2 variant from samples collected between October 15 and November 25, 2020, in three provinces. By early November, this variant rapidly became the dominant variant in samples from two provinces. The researchers suggested that this may be due to increased transmissibility or immune escape.

“Each SARS-CoV-2 variant has specific mutations defining it,” Dr Alisoltani-Dehkordi said. “Professor Godzik and I used computer modeling to suggest possible structural and functional consequences of spike protein mutations in the SA lineage. Our analysis, confirmed also by several other research groups, shows that some of the mutations potentially result in a higher transmissibility of the virus and a weaker immune response.”

The SA variant has been detected in 40 countries, and is quite likely present in more still.

“This variant is probably spreading in areas where it has not been sequenced and is, therefore, not identifiable,” Prof Godzik said. “In the US, sequencing is still a slow process. In many parts of the country, including Riverside, we have no information whatsoever about variants.”

The SA variant prompted concern among scientists because its mutations allowed it to evade antibody protection, and potentially, vaccines. Indeed, the AstraZeneca vaccine rollout was halted in South Africa due to the low level of protection against this new variant.

“That’s when it received a high level of interest,” Prof Godzik said. “Subsequent research confirmed it is resistant to vaccines and is spreading. South Africa is doing a good job, however, at controlling the variant through quarantining and other measures.”

Common mutational signatures can be seen in each of the newly emerged SARS-CoV-2 variants of concern in the UK, SA, Brazil, and California. But each of these variants also has a unique set of mutations; for example, the SA and Brazil variants have two unique mutations on spike proteins K417N and E484K, respectively. But, as Prof Godzik explains, there is no single “SA variant”, rather a branch on an evolutionary tree. And viruses can acquire mutations and escape at any time.

Prof Godzik thinks COVID will become a permanent feature of our lives. “It takes six months to develop a flu vaccine,” he said. “Models predict the evolution of the flu virus and vaccines are produced before the variants show up. If the predictions are good, the vaccines work. If they miss, a heavy flu season follows. This is how COVID will likely behave. A lot of effort will be invested in predicting what will happen the following year, vaccines would then be updated, and people will need to get a booster shot.”

Source: University of Riverdale, California

Categories : Immune System New Compounds and TreatmentsTags :

New Compound Can Reduce Inflammation Without Dampening Immune Response

On By ModernMedia

Researchers from Nanyang Technological University (NTU), Singapore, have discovered a compound that is capable of dampening immune overactivity without the cost of reducing the immune response.

The new compound, ASO-1, targets tyrosine kinase 2 (TYK2), a member from the Janus kinase (JAK) family of enzymes involved in immune response regulation. These enzymes have received attention in recent years as targets for drugs to treat immune system overactivity, and TYK2 is a possible therapeutic target for cancer treatment. A recent study found that high levels of TYK2 have been associated with severe COVID.

“Human genetic studies have suggested that deactivating TYK2 could provide protection against a broad range of autoimmune conditions such as rheumatoid arthritis, psoriasis, lupus, and type 1 diabetes,” said Phan Anh, Professor and Interim Director, Institute of Structural Biology, NTU.

Co-lead author Dr Lim Kah Wai, NTU senior researcher, added: “With the UK-led study of critically ill COVID patients published in Nature linking high TYK2 expression to severe COVID, ASO-1 could be a therapeutic agent worth investigating further. We are planning to conduct further pre-clinical work to validate its therapeutic potential.”

The ASO-1 compound designed by the researchers is an antisense oligonucleotide (ASO), which targets messenger RNA (mRNA).  ASO-1 was identified from over 200 potentially effective ASOs designed by the team.  ASO-1 is designed to bind to TYK2 mRNA and prevent the cells from making the TYK2 protein. ASO-1 has to be highly selective for TYK in order to prevent side effects involving other JAK enzymes.

Through in vitro testing, the NTU scientists found that ASO-1 greatly reduced TYK2 levels over a sustained period and inhibited immune signalling pathways associated with autoimmune disorders. This points to the potential of the ASO-1 compound forming the basis for treatment of autoimmune conditions, There was also no effect against the other JAK proteins. Dr Lim noted that this high potency of ASO-1 rivals that of recent ASO drug candidates under development.

The team plans academic collaboration for further development of ASO-1 and animal model testing.

Source: News-Medical.Net