Year: 2021

Categories : CancerTags :

Pre-op Immune Checkpoint Inhibition in Lung Cancer

On By ModernMedia

According to a prospective multicenter trial, one fifth of patients with operable early-stage non-small cell lung cancer (NSCLC) had major pathologic responses (MPR) and over 40% had pathologic downstaging after neoadjuvant atezolizumab.

Out of 144 patients, 30 achieved MPR (defined as ≤10% viable tumour cells), 10 of whom had pathologic complete response (pCR), while 66 experienced downstaging and upstaging occurred in 29. 

Jay M Lee, MD, of the David Geffen School of Medicine at the University of California Los Angeles, explained: “The LCMC (Lung Cancer Mutation Consortium)3 study successfully met its primary endpoint of achieving major pathologic response in 21% of patients, and a pathologic complete response rate of 7%. Neoadjuvant atezolizumab monotherapy was well tolerated, with no new safety signals, and resection was performed with low perioperative morbidity and mortality, usually within a narrow protocol window, with a short time frame from completion of atezolizumab and with a corresponding high R0, or complete resection rate.”

Some 90% of patients were still alive at 18 months, and 80% were disease-free and alive. The findings indicate that neoadjuvant therapy with an immune checkpoint inhibitor (ICI) is possible thought it does make surgery harder, said invited discussant Shinichi Toyooka, MD, of Okayama University Hospital. Similar outcomes were seen in patients with stage I-II versus stage III disease, although survival data is currently lacking, requiring follow-up to find out if single-agent ICI is sufficient for all patients with operable NSCLC.

“I think single ICI can be used for early-stage disease and poor performance status,” said Toyooka. “On the other hand, a combination of ICI and chemotherapy is suitable for advanced-but-resectable cases.”

Minimally invasive surgery (robotic or VATS) was successful in 86 patients, and 15 others required conversion to thoracotomy. Lee said 79% of patients underwent lobectomy, and 3% had segmentectomy or wedge procedures. R0 (clear surgical margins) status was achieved in 92% of the 159 patients who went to surgery.

The trial included 181 patients with newly diagnosed, resectable stage Ib-IIIa and selected IIIb (T4 because of mediastinal invasion) NSCLC and no targetable mutations, of which 159 underwent surgery. 15 patients were later found to have EGFR/ALK-positive disease and excluded from analysis. Patients had radiographic staging before and after two cycles of atezolizumab and then underwent surgery within 30 to 50 days after finishing neoadjuvant therapy.

Minimally invasive surgery (robotic or VATS) was successful in 86 patients, and 15 others required conversion to thoracotomy; 79% of patients underwent lobectomy, and 3% had segmentectomy or wedge procedures. R0 (clear surgical margins) status was achieved in 92% of the 159 patients who went to surgery.

Source:MedPage Today

Presentation reference: Lee JM, et al “Surgical and clinical outcomes with neoadjuvant atezolizumab in resectable stage Ib-IIIb NSCLC: LCMC3 trial primary analysis” WCLC 2020; Abstract PS01-05.

Categories : Cardiovascular Disease GenderTags :

Women are Less Likely to Undergo Critical Heart Surgery

On By ModernMedia

A scientific presentation at the 57th Annual Meeting of The Society of Thoracic Surgeons revealed that women are less likely to have a coronary artery bypass grafting (CABG) using guideline-recommended approaches, possibly resulting in worse post-surgery outcomes.

CABG is a major surgical operation involves bypassing atheromatous blockages in a patient’s coronary arteries with venous or arterial conduits harvested from elsewhere in the patient’s body.

Dr Oliver Jawitz and colleagues from Duke and The Johns Hopkins University School of Medicine used the STS Adult Cardiac Surgery Database (containing records of nearly all CABG procedures done in the US), and identified adult patients from 2011 to 2019 who underwent first-time isolated CABG, along with detailed demographic, clinical and procedural data.

The association between female sex and three different CABG surgical techniques from US and European guidelines was investigated. Grafting of the left internal mammary artery to the left anterior descending artery, complete revascularisation, and multiarterial grafting have been linked to better short and/or long-term outcomes. Despite this, the results indicated that women were 14%-22% less likely than men to undergo CABG procedures with these revascularisation strategies.

“With these findings, we did in fact see less aggressive treatment strategies with women,” said Dr Jawitz. “It is clear that sex disparities exist in all aspects of care for patients with coronary artery disease (CAD), including diagnosis, referral for treatment, and now, in surgical approaches to CABG. We must ensure that female patients undergoing CABG are receiving evidence-based, guideline-concordant techniques.”

The results are in accordance with an overall neglect of heart disease treatment in women. Women are much more likely than men to have non-typical symptoms of heart disease which are also subtler, such as abdominal pain and fatigue, as well as having their own particular set of risk of factors. This is compounded by women being underrepresented in cardiac disease study cohorts.

Women’s health historically focused on mother and child, and breast cancer. As such, the period from symptom onset to diagnosis and treatment is longer, allowing the disease to progress and worsen outcomes. This is also reflected by fewer women being referred for beneficial treatments such as CABG. 


“Delayed diagnosis of CAD in women leads to late initiation of key behavioral and pharmacologic interventions for minimizing heart disease risk, as well as delayed referral for invasive diagnostic and therapeutic procedures, including surgical revascularisation with CABG,” said Dr Jawitz. “This often means that by the time female patients undergo these procedures, they have more severe disease than males, as well as a greater number of comorbidities, which leads to worse outcomes.

“Now that we have identified specific differences in surgical approaches to CABG between females and males, we must further elucidate how these differences result in disparate outcomes such as increased mortality, readmissions, and complications,” he concluded. “These findings will help inform the development of sex-specific guidelines for the diagnosis and management of cardiovascular disease.”

Source: News-Medical.Net

Categories : COVIDTags :

New Single-dose Intranasal Vaccine Shows Promise

On By ModernMedia

A new, single dose intranasal vaccine has shown ability to protect Macaques against COVID, as reported in a preprint article on bioRxiv. If it proves effective and safe in humans, it could be a radically effective and simple to administer vaccine against COVID.

Currently, most COVID vaccines are administered intramuscularly and require two doses. However, after immunisation, an infected person can still shed the virus from the upper airways because they do not have local or mucosal immunity, as demonstrated by intramuscular vaccination in non-human primates.

The SARS-CoV-2 virus enters the target the host cell by the spike (S) protein antigen locking on to the cell’s angiotensin-converting enzyme 2 (ACE2) receptor. Thus, the S protein is a critical target for vaccine development.The researchers developed the new vaccine uses a chimpanzee adenovirus which expresses the S protein (ChAd-SARS-CoV-2-S). The chimpanzee adenovirus (also used in the AstraZeneca vaccine) is ideal as an antigen carrier for vaccines as the prevalence of neutralising antibodies against it is low. 

In the researchers’ previous work, the vaccine had been administered intranasally to mice with expressed human ACE2 receptors, producing a detectable immune response. The researchers then moved experimentation on to macaques, administering a single intranasal dose of vaccine, followed by intranasal and intrabroncheal challenge with SARS-CoV-2.

A detectable immune response was detected by the presence of anti-S, anti-RBD, and neutralising antibodies, as well as T cell responses. Viral RNA loads measured by nasal swabs were lower in immunised animals, with only one having detectable virus presence, compared to four of six control animals. These results suggest that local infection is prevented, with reduced viral RNA levels and faster viral clearing. 

Infection was also measured in broncheal alveolar lavage fluid (BALF)At day seven, immunised animals showed lower viral DNA than controls, corresponding to increased neutralising antibody levels.

Administering the vaccine intranasally could allow protection of the local and surrounding tissues, while reducing disease severity and spread to others. However, the lack of severe pathologies in both sets of animals means that no conclusions can be drawn about the vaccine’s effectiveness in preventing against COVID.

Further research is required to compare the effects of intramuscular and intranasal administration of the vaccine, and the work is yet to be peer reviewed.

Source: News-Medical.Net

Journal information: Hassan, A. O. et al. (2021). A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques. bioRxiv preprint. doi: https://doi.org/10.1101/2021.01.26.428251. https://www.biorxiv.org/content/10.1101/2021.01.26.428251v1

Categories : COVIDTags :

Ramaphosa to Take Delivery of SA’s First Vaccine Doses

On By ModernMedia

President Cyril Ramaphosa will take delivery of the first million doses arrives in South Africa at OR Tambo airport on Monday.

Ramaphosa will be accompanied by Deputy President David Mabuza, Health Minister Zweli Mkhize and the High Commissioner of India. After the vaccine has been received, it will be taken to cold storage for and undergo technical processing and quality testing.

Acting spokesperson for the Presidency, Tyrone Seale, said: “The arrival of the fist consignment at OR Tambo International Airport marks the start of the vaccine roll-out, which President Ramaphosa describes as the largest and most complex logistical vaccine undertaking in South Africa’s history.”

The AstraZeneca doses were produced by the Serum Institute of India, and healthcare workers will be the first to be vaccinated, with essential workers second on the list. However, the Department of Health has suggested that politicians (who are classified as essential workers) may be the first to receive the vaccine, in order to reassure the public and encourage vaccine uptake. An additional 500 000 doses are to be delivered in February.

There are fears that current vaccines are less effective against the B1.351 “South African” variant. The Novovax vaccine has been shown to have slightly less than 50% effectiveness in South African trials, due to the variant and the prevalence of HIV in the population. Johnson & Johnson’s vaccine, which is set to be produced locally by Aspen, is around 57% effective in South Africa. These are about what is achieved with annual flu vaccines, which are 40-60% effective. The AstraZeneca AZD1222 vaccine developed in concert with Oxford University have been shown to be 70% effective in clinical trials, although this was prior to the widespread emergence of COVID variants. However, it is possible to adjust vaccines to to deal with the new variants, with Dr Anthony Fauci saying that this reduced vaccine effectiveness against variants is a “wake-up call”.

The Azstra Zeneca vaccine uses a non replicating viral vector to deliver genetic information to cells, instructing them to produce the spike protein of the SARS-CoV-2 virus to train the immune system to recognise it and build immunity. It requires two doses administered four weeks apart, and unlike many other vaccines, does not require storage at extremely cold temperatures – only requiring normal refrigeration at 2° to 8°C.

Source: Eyewitness News

Categories : Gender Mental HealthTags :

Protein ‘Flavours’ Cause Gender Difference in Psychiatric Drug Responses

On By ModernMedia

A new study has shown that different isoforms or ‘flavours’ of key proteins have different effects in males and females, causing psychiatric drugs to function well in one gender and in others to be ineffective or a have host of side effects.

“The ultimate goal is to find the kink in the armor of mental illness—the proteins in the brain that we can specifically target without impacting other organs and causing side effects,” explained Charles Hoeffer, an assistant professor of integrative physiology at the Institute for Behavioral Genetics. “Personalisation is also key. We need to stop hitting every mental illness with the same hammer.

AKT was discovered in the 1970s and known as a gene which resulted in cancer when mutation was present. It is now known to play a role in “synaptic plasticity”, where synaptic connections between neurons are strengthened to encode memories.

“Let’s say you see a shark and you’re scared and your brain wants to form a memory. You have to make new proteins to encode that memory,” explained Hoeffer.

Different isoforms have different functions in the brain; AKT1 together with AKT2 in the prefrontal cortex is important for making new memories.
“These subtle differences could be really important if you wanted to personalise treatments for people,” explained Marissa Ehringer, an associate professor of integrative physiology who partnered with Hoeffer on some of the research.

The researchers spent six years examining the brains of male and female animals, and the role the loss of AKT played. For example, male mice with functioning AKT1 were much better than those without AKT1 when it came to “extinction learning”—replacing an old memory, or association that is no longer needed. However, in female mice, not having AKT1 did not make much difference.

“We found the difference between males and females to be so great it became the focus of our work,” Hoeffer said. “It was like night and day.”

Although there is much still to be learned, Hoeffer suspects that there are many other such key proteins having different effects or purposes in males and females.  

“To help more people suffering from mental illness we need much more knowledge about the difference between male and female brains and how they could be treated differently,” Hoeffer said. “This study is an important step in that direction.”

Source:Medical Xpress
Journal information: Helen Wong et al. Isoform-specific roles for AKT in affective behavior, spatial memory, and extinction related to psychiatric disorders, eLife (2020). DOI: 10.7554/eLife.56630

Categories : Cancer GeneticsTags :

New Method to Pick up Mutations Behind Colorectal Cancer Risks

On By ModernMedia

University of Michigan researchers have developed a method to detect mutations which give rise to colorectal cancer.

Colorectal cancer is the third most common cancer type, and the second most common cause of cancer-related deaths in the United States. Although most cases occur sporadically, some 5 to 10% of cases are hereditary, the most common cause of which is Lynch syndrome. Lynch syndrome results in an 80% increase in the lifetime risk of developing colorectal cancer. Those with a family history of colorectal cancer are advised to start screening before age 45. However, genetic testing for cancer risk does not always provide useful information for those with family history.  

To address this, a new method of genetic testing was developed by Jacob Kitzman, PhD, of the Department of Human Genetics at Michigan Medicine plus together with other colleagues. Since mutations are rare in the human population, determining which one is responsible is difficult, and simply studying one in the lab is too time consuming to be practical.
With deep mutational scanning, the researchers measured the effect of MSH2 mutations, which is one major cause of Lynch syndrome

They deleted the normal copy of MSH2 from human cells with CRISPR-Cas, replacing it with a library of every possible mutation in the MSH2 gene. Each cell in the mix then carried a unique MSH2 mutation. Chemotherapy then killed off only the cells that had a functional variant of MSH2.

The counterintuitive idea, noted Kitzman, is that the surviving cells do not have functioning MSH2—which have mutations that are most likely to cause disease.

“We were basically trying to sit down and make the mutations we could so they could serve as a reference for ones that are newly seen or are amongst the thousands of variants of unknown significance identified in people from clinical testing,” says Kitzman. “Until now, geneticists could not be sure whether these are benign or pathogenic.”

It is hoped that with other patient-specific information, some of these variants could be reclassified, and those individuals advised to undergo more intense screening.

Kitzman said: “One of the next areas that will need some focus in the field of human genetics is to create these sorts of maps for many different genes where there is a clinical connection, so we can be more predictive when variants are found in an individual.”

Source: Medical Xpress

Journal information: Xiaoyan Jia et al, Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk, The American Journal of Human Genetics (2020). DOI: 10.1016/j.ajhg.2020.12.003

Categories : Diet and Nutrition GastrointestinalTags :

Underweight and Gastrointestinal Distress – A Bidirectional Relationship?

On By ModernMedia

An Asian cross-sectional study found that underweight was linked to functional dyspepsia (FD), regardless of the presence of anxiety, although anxiety was additionally associated with FD.

The study by Kee Huat Chuah, MD, of the University of Malaysia in Kuala Lumpur, and colleagues, also found no link between high body mass index (BMI) and other functional gastrointestinal disorders (FGIDs). People with FGIDs often have irritable bowel syndrome, functional dyspepsia, or functional constipation. These conditions affect up to 40% of people at any one point in time, two-thirds will have chronic, fluctuating symptoms. The questionnaire-based study recruited 1002 adult individuals with a median age of 32, with 20.7% having FGID according to the Rome III criteria.

Across different FGIDs, including irritable bowel syndrome (IBS) and functional diarrhea and constipation, FD affected more underweight adults (defined as BMI less than 18.5) compared with a non-FGID control group (13.3% vs 3.5%, P=0.002). Multivariate analysis showed that underweight maintained an independent association with FD, at an odds ratio (OR) of 3.648 (95% CI 1.494-8.905, P=0.004).

The results of a large population study from France were consistent with these findings, which also found that being underweight was independently associated with FD in females.  Diarrhoea may also have been associated with central obesity, but there were too few individuals with diarrhoea to draw conclusions, although a large US population study from 2019 showed that obesity was associated with chronic diarrhoea.

A bidirectional association has been observed in eating disorders (often linked with anxiety disorders) with both a low BMI and FD.  Anxiety and/or eating disorders may have caused FD subjects to have a low BMI.

William D Chey, MD, of Michigan Medicine, who was not involved with the research, said the results were interesting and that they could be applicable to the US population since obesity rates are comparable to those in Malaysia.

“But I do agree it’s important to consider whether these observations are cause or effect,” Chey commented. “In other words, FD might cause people to lose weight or thin people might be more prone to developing FD. I do think there’s face validity to these observations. Remember that patients with functional dyspepsia that have meal-related symptoms of fullness and early satiety are unable to eat very much without feeling ill.”

Patients with postprandial distress syndrome often lose weight as a result, Chey continued. “On the other hand, patients with anorexia often have measurable abnormalities in gastric emptying, but that’s not to say all FD patients have eating disorders. My point is that certain non-GI conditions associated with weight loss can also be associated with abnormal GI function.”

The team called for further studies of longitudinal design to explore whether anxiety causes a low BMI in FD or vice versa. Limitations included not being population based, with the cohort being mostly hospital and university staff members. In addition, the data on psychological disorders came from a subgroup of original participants in the study’s second phase; the number of participants with functional diarrhoea was low; the cross-sectional design did not allow for causality; and the questionnaire only asked about dietary habits.

Source: MedPage Today

Journal information: Beh KH, et al “The association of body mass index with functional dyspepsia is independent of psychological morbidity: a cross-sectional study” PloS One 2021; doi: 10.1371/journal.pone.0245511.

Categories : Ageing Neurodegenerative DiseasesTags :

Obesity Adds to Alzheimer Severity

On By ModernMedia

In addition to it being a risk factor for many known chronic diseases, obesity is an additional burden on cerebral health and may also be associated with the progression of Alzheimer’s disease, according to a new study from the University of Sheffield and the University of Eastern Finland.  

The study used multimodal neural imaging and showed that obesity may contribute to the vulnerability of neural tissue, while maintaining a healthy weight helped to maintain brain structure in mid dementia Alzheimer’s disease.

Alzheimer’s disease is a neurodegenerative disease which accounts for two thirds of dementia in over 65s, is the sixth leading cause of death in the United States and there is no cure at present.  

Lead author Professor Annalena Venneri from the University of Sheffield’s Neuroscience Institute and NIHR Sheffield Biomedical Research Centre, said: “More than 50 million people are thought to be living with Alzheimer’s disease and despite decades of ground breaking studies and a huge global research effort we still don’t have a cure for this cruel disease.

“Prevention plays such an important role in the fight against the disease. It is important to stress this study does not show that obesity causes Alzheimer’s, but what it does show is that being overweight is an additional burden on brain health and it may exacerbate the disease.”

She added that it was important to educate people early on in their lives as it was too late to wait until the 60s to lose weight as the disease lurks in the backgrounds.

The researchers examined MRI scans of the brains of 47 patients diagnosed with mild Alzheimer’s disease dementia, 68 patients with mild cognitive impairment, and 57 individuals who were cognitively healthy. Using three complementary, computational techniques, they studied the brain’s anatomy, blood flow and also the brain’s fibres.

They compared gray matter volume, white matter integrity, cerebral blood flow and obesity. Grey matter volume decreases in Alzheimer’s. In patients with mild Alzheimer’s, an association was found with obesity and grey matter volume around the right temporoparietal junction, suggesting obesity creates a neural vulnerability in cognitively impaired patients. The study also found that maintaining a healthy weight may help preserve brain structure in structure in the presence of age and disease-related weight loss.

Joint author Dr Matteo De Marco from the University of Sheffield’s Neuroscience Institute, said: “Weight-loss is commonly one of the first symptoms in the early stages of Alzheimer’s disease as people forget to eat or begin to snack on easy-to-grab foods like biscuits or crisps, in place of more nutritional meals.

“We found that maintaining a healthy weight could help preserve brain structure in people who are already experiencing mild Alzheimer’s disease dementia. Unlike other diseases such as cardiovascular disease or diabetes, people don’t often think about the importance of nutrition in relation to neurological conditions, but these findings show it can help to preserve brain structure.”

Source: Medical Xpress

Journal information: Manmohi D. Dake et al, Obesity and Brain Vulnerability in Normal and Abnormal Aging: A Multimodal MRI Study, Journal of Alzheimer’s Disease Reports (2021). DOI: 10.3233/ADR-200267

Categories : COVIDTags : 1 Comment

Ivermectin Approved to Treat COVID in SA on Limited Basis

On By ModernMedia

Ivermectin, which has some reports of high effectiveness in limited studies, has received approval from the SA government to be used under strict control for compassionate use.  

Dr Boitumelo Semete-Makokotlela, head of the South African Health Products Regulatory Authority (SAHPRA), said that practitioners applying to use the drug will be considered case-by-case.

Ivermectin has a long history of use as an antiparasitic treatment in animals, while in humans it’s used as an anthelmintic drug that is usually indicated for filarial and resistant scabies infections. While the World Health Organization has suggested the drug has encouraging effects on coronavirus, although it hasn’t been properly evaluated yet.

“We absolutely share everyone’s desperation at this point,” said Helen Rees, SAHPRA chairwoman. “So the question about ivermectin and self-medication goes back to what everyone in the scientific community is saying. And that is, we don’t know if it works and we don’t know if it doesn’t work. That’s why we need to get data.”

Physicians in Zimbabwe are reportedly treating COVID with ivermectin in combination with silver nanoparticles – normally used as an algaecide – to great success.

Rees, however, warned South Africans that people self-medicating “need to be very careful because we don’t have any information about the quality of what you’re taking.”

Dr Semete-Makokotlela said that clear guidelines for the rollout would be given tomorrow. She added that SAHPRA granted the health department permission to distribute the Oxford/AstraZeneca COVID vaccine, the first one for SA. It is also currently reviewing applications from Johnson & Johnson and Pfizer, but has yet to receive an application from Moderna, she said.

Source: BusinessTech

Categories : COVID HIVTags :

Novavax COVID Vaccine only 49.4% Effective in SA

On By ModernMedia

On Thursday, Novavax announced that its vaccine was 89% effective, according to its UK trials which had 15 000 participants. However, its SA trials showed a much lower effectiveness of 49.4%, believed to be caused by the SA COVID variant B.1.351 (aka 501.V2). 

The company conveyed the information in a press release, with a detailed journal publication still to come. The SA trial had 4400 participants, and the observed protection varied depending on HIV status. In people who were HIV negative, the vaccine conferred 60% protection. If the vaccination trial included a representative proportion of HIV positive adult South Africans, it may mean that its effectiveness for this vulnerable segment is very low.

“The higher efficacy of the vaccine in the UK than in South Africa is because the variants circulating in SA are less sensitive to vaccine induced immune responses,” said Professor Shabir Madhi, Executive Director of the Vaccines and Infectious Diseases Analytics Research Unit (VIDA) at Wits, and principal investigator in the Novavax COVID vaccine trial in SA.

“Nevertheless, the 60% reduced risk against Covid-19 illness in vaccinated individuals in South Africans underscores the value of this vaccine to prevent illness from the highly worrisome variant currently circulating in South Africa, and which is spreading globally. This is the only Covid-19 vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa.”

Novavax is pressing ahead with a trial involving 30 000 participants in the United States and Mexico, and has shared data with the UK’s pharmaceutical regulator. It is not clear whether the data from the US and Mexico trial will be required before the vaccine receives approval there. Meanwhile on Friday, the Johnson & Johnson vaccine developed by its subsidiary Janssen has been shown to be 66% effective. It is a single dose vaccine with minimal refrigeration requirements, making it very important for the logistical challenge of vaccinations in developing countries. Since Aspen would be producing some of the doses locally, the SA government had been in talks with Johnson & Johnson to secure some of those vaccines for SA use. However, there are signs that it too is less effective against the B.1.351 variant.

Source: Business Insider