Day: February 1, 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