Day: February 1, 2024

Murder-accused Paediatric Surgeon Advised that Procedures Were Unnecessary

Photo by Tingey Injury Law Firm on Unsplash

A state witness in the trial of murder accused Dr Peter Beale has testified that colleagues advised him against a procedure which led to the death of a three year old patient.

Paediatric surgeon Beale is charged with three counts of murder, as a result of deaths from unnecessary surgeries over 2012 to 2019. He is also charged with two counts of fraud. He was first arrested in 2019, with his trial date postponed multiple times and only getting underway this week Monday in Johannesburg. His co-accused, anaesthetist Dr Abdulhay Munshi, was shot dead in 2020. As a result of the case, some have voiced concerns over what could lead to criminalisation over deaths resulting from unavoidable errors and systemic failures.

Two of the three deaths stemmed from laparoscopic Nissen fundoplication, a complex and costly procedure that is usually used to treat GERD by tightening the junction of the oesophagus and stomach.

According to the indictment, Beale is accused of “unlawfully and intentionally” causing the deaths of a three-year-old boy in 2012, a 21-month-old girl in 2016 and a 10-year-old boy in 2019 after he had operated on the children.

The state contends that Beale performed these unnecessary procedures as he needed money to recover from heavy financial losses incurred in a failed investment in the 1990s.

News24 reports that, based on a rectal biopsy, Beale believed that the three year old boy had Hirschsprung’s Disease, requiring surgical intervention. As reported in Beeld, Beale said in his plea explanation that he “misread” the patient’s biopsy results and did not deliberately misrepresent the biopsy results to the parents.

The parents sought a second opinion, the state alleges, and the second doctor was hesitant about carrying out the procedure. Beale was able to convince the other doctor that the procedure was necessary based on the biopsy results. Beale also explained in his plea deal that there was a variant of the disease, and the treatment was the same. His counsel, Advocate Ian Greene, also pointed out that the pathologist testified at a disciplinary hearing that the biopsy did not exclude the variant even if it did not exclude Hirschsprung’s Disease.

According to News24, a state witness, who is another paediatric surgeon who remains anonymous at the court’s order, stated that Beale had tried to recruit him to a Ponzi scheme. The scheme had a joining fee of R1 million.

The witness, who had know Beale since 1996, said that in 2009, the accused had also confided in him at a conference that he had suffered significant losses in an investment. The witness was also on the committee at the Healthcare Practitioners’ Council of South Africa disciplinary hearing over the three-year-old’s death. Beale has since been struck from the HPCSA.

The South African Medical Association released a statement urging that, while tragic, the case highlights laws that criminalise and punish individuals instead of taking into account the various organisational failings that can lead to patient deaths and can in no way prevent “unavoidable errors”.

Note: this article has been updated to correct the number of laparoscopic Nissen fundoplication procedures and to add more information about the Hirschsprung’s Disease diagnosis.

The Neural Circuits that Manage the Balancing Act of Hydration

Credit: Pixabay CC0

The human brain regulates water and salt appetite to maintain proper hydration. A new study published in Cell Reports reveals how the brain’s centre for digestive signals has two distinct neuronal populations that regulate either salt or water intake.

Previous studies suggested that water or salt ingestion quickly suppresses thirst and salt appetite before the digestive system absorbs the ingested substances, indicating the presence of sensing and feedback mechanisms in digestive organs that help real-time thirst and salt appetite modulation in response to drinking and feeding. Unfortunately, despite extensive research on this subject, the details of these underlying mechanisms remained elusive.

To shed light on this matter, a research team from Japan has recently conducted an in-depth study on the parabrachial nucleus (PBN), the brain’s relay centre for ingestion signals coming from digestive organs.

The researchers conducted a series of in vivo experiments using genetically engineered mice.

They introduced optogenetic (and chemogenetic) modifications and in vivo calcium imaging techniques into these mice, enabling them to visualise and control the activation or inhibition of specific neurons in the lateral PBN (LPBN) using light (and chemicals). During the experiments, the researchers offered the mice, either in regular or water- or salt-depleted conditions, water and/or salt water, and monitored neural activities along with the corresponding drinking behaviours.

In this way, the team identified two distinct subpopulations of cholecystokinin mRNA-positive neurons in the LPBN, which underwent activation during water and salt intake.

The neuronal population that responds to water intake projects from the LPBN to the median preoptic nucleus (MnPO), whereas the one that responds to salt intake projects to the ventral bed nucleus of the stria terminalis (vBNST). Interestingly, if the researchers artificially activated these neuronal populations through optogenetic (genetic control using light) experiments, the mice drank substantially less water and ingested less salt, even if they were previously water- or salt-deprived.

Similarly, when the researchers chemically inhibited these neurons, the mice consumed more water and salt than usual.

Therefore, these neuronal populations in the LPBN are involved in feedback mechanisms that reduce thirst and salt appetite upon water or salt ingestion, possibly helping prevent excessive water or salt intake.

These results, alongside their previous neurological studies, also reveal that MnPO and vBNST are the control centres for thirst and salt appetite, integrating promotion and suppression signals from several other brain regions.

“Understanding brain mechanisms controlling water and salt intake behaviours is not only a significant discovery in the fields of neuroscience and physiology, but also contributes valuable insights to understand the mechanisms underlying diseases induced by excessive water and salt intake, such as water intoxication, polydipsia, and salt-sensitive hypertension,” remarks first author, Assistant Professor Takashi Matsuda from Tokyo Institute of Technology.

Source: Tokyo Institute of Technology

Radon Gas: Ubiquitous, Carcinogenic – and Possible Stroke Risk

Photo by Vladyslav Cherkasenko on Unsplash

A new study has found that exposure to radon, the second leading cause of lung cancer, is also linked to an increased risk of stroke. The study, which examined exposures in middle age to older female participants, found an increased risk of stroke among those exposed to high and even moderate concentrations of the gas compared to those exposed to the lowest concentrations. The study is published in Neurology®, the medical journal of the American Academy of Neurology.

Radon is a naturally occurring radioactive gas produced in certain rocks and soils which contain uranium or radium. In South Africa, some areas such as in the Western Cape have higher concentrations of radon due to underlying granite geology. It is also a concern near gold mine dumps, which have higher levels of uranium.

The gas can make its way into homes through cracks in basement walls and floors, construction joints and gaps around pipes.

“Radon is an indoor air pollutant that can only be detected through testing that measures concentrations of the gas in homes,” said study author Eric A. Whitsel, MD, MPH, of the University of North Carolina in Chapel Hill.

“Our research found an increased risk of stroke among participants exposed to radon above – and as many as two picocuries per litre (pCi/L) below – concentrations that usually trigger Environmental Protection Agency recommendations to install a home radon mitigation system.”

The study involved 158 910 female participants with an average age of 63 who did not have stroke at the start of the study.

They were followed for an average of 13 years. During the study, there were 6979 strokes among participants.

To determine radon exposures, researchers linked participants’ home addresses to radon concentration data from the U.S. Geological Survey and the U.S. Environmental Protection Agency (EPA).

The EPA recommends that average indoor radon concentrations do not exceed four picocuries per liter (pCi/L). For concentrations this high, the EPA recommends installing a radon mitigation system to lower radon levels in the home.

Participants were divided into three groups. The highest group had homes in areas where average radon concentrations were more than four pCi/L. The middle group lived in areas with average concentrations between two and four pCi/L. The lowest group lived in areas with average concentrations of less than two pCi/L.

In the group with the highest radon exposures, there were 349 strokes per 100 000 person-years compared to 343 strokes in the middle group and 333 strokes in group with the lowest exposure.

Person-years represent both the number of people in the study and the amount of time each person spends in the study.

After adjusting for factors such as smoking, diabetes and high blood pressure, researchers found participants in the highest group had a 14% increased risk of stroke compared to those in the lowest group.

Those in the middle group had a 6% increased risk.

“It’s important to note that we found an increased stroke risk among those exposed to radon concentrations as much as two pCi/L below the current lung cancer-based threshold for recommending radon mitigation,” said Whitsel.

“More studies are needed to confirm our findings. Confirmation would present an opportunity to improve public health by addressing an emerging risk factor for stroke.”

A limitation of the study was that it included only female participants who were middle age or older and primarily white, so the results may not be the same for other populations.

Source: American Academy of Neurology

No Difference in Short-term Complications for Obesity Surgeries

Sleeve gastrectomy. Credit: Scientific Animations CC4.0

The two most common obesity surgeries, gastric bypass and gastric sleeve, have few short-term complications and show no significant differences, according to study findings published in the journal JAMA Network Open. These are the first results of a multicentre randomised controlled trial comparing obesity surgeries conducted by the University of Gothenburg.

Patients undergoing obesity surgery will normally have a BMI of at least 40, or 35 if they also have other serious medical conditions related to obesity.

The most common procedures are gastric bypass, where a large part of the stomach and part of the small intestine are bypassed, and gastric sleeve, where a large part of the stomach is surgically removed.

The aim of the current study was to compare the short-term risks of the different procedures.

The study is the largest of its kind. 1735 adult patients planned for surgery in Norway and Sweden between 2015 and 2022 agreed to participate, and they were randomly assigned to either gastric bypass or gastric sleeve.

Relatively few complications

Surgical time was longer for gastric bypass, averaging 68 minutes compared to 47 minutes for gastric sleeve, but hospitalisation after surgery was one day regardless of method.

The follow-ups also gave equivalent results for the two methods.

At 30 days after surgery, both groups had relatively few complications such as haemorrhage, leakage, blood clots and infections.

No deaths occurred during the follow-up period of a total of 90 days.

“For both surgical procedures, the risk of complications is very low, especially from an international perspective, and there is no statistically significant or clinically relevant difference between the groups,” says Suzanne Hedberg, first author of the study.

Many stakeholders and many opinions

“Many people have had surgery, or are on waiting lists for surgery, and there are lots of discussions and opinions about the different methods. What the study shows is that patients and doctors can now choose their surgical method without considering short-term surgical risks,” she says.

Suzanne Hedberg defended her thesis in surgery at Sahlgrenska Academy, University of Gothenburg in April 2023, and is a consultant at Sahlgrenska University Hospital.

The study, included in her thesis, is the first publication with results from BEST (Bypass Equipoise Sleeve Trial), a Scandinavian registry-based randomised controlled multicentre study comparing the two methods of obesity surgery.

The main outcome of the trial which analyses the risk of complications and weight progression over 5 years, is expected to be completed in 2028.

“For the ongoing studies, we are off to a good start with equivalent groups, laying a good foundation for further comparisons of more long-term results,” concludes Suzanne Hedberg.

Source: University of Gothenburg

The Soapbark Tree Was the Only Source of a Potent Vaccine Adjuvant – Until Now

Photo by Louis Reed on Unsplash

A molecule derived from the Chilean soapbark tree is a potent adjuvant now used in many vaccines, such as Mosquirix and Novavax. Now, it has been reported in Nature Chemical Biology that scientists have replicated it in an alternative plant host for the first time, opening unprecedented opportunities for the vaccine industry and relieving pressure on this limited natural source.

A research collaboration led by the John Innes Centre used the recently published genome sequence of the Chilean soapbark tree (Quillaja saponaria) to track down and map the elusive genes and enzymes in the complicated sequence of steps needed to produce the molecule QS-21.

Using transient expression techniques developed at the John Innes Centre, the team reconstituted the chemical pathway in a tobacco plant, demonstrating for the first time ‘free-from ‘tree’ production of this highly valued compound.

Professor Anne Osbourn FRS, group leader at the John Innes Centre said: “Our study opens unprecedented opportunities for bioengineering vaccine adjuvants. We can now investigate and improve these compounds to promote the human immune response to vaccines and produce QS-21 in a way which does not depend on extraction from the soapbark tree.”

Vaccine adjuvants are immunostimulants which prime the body’s response to the vaccine – and are a key ingredient of human vaccines for shingles, malaria, and others under development.

QS-21, a potent adjuvant, is sourced directly from the bark of the soapbark tree, raising concerns about the environmental sustainability of its supply.

For many years researchers and industrial partners have been looking for ways to produce the molecule in an alternative expression system such as yeast or tobacco plants.

But the complex structure of the molecule and lack of knowledge about its biochemical pathway in the tree have so far prevented this.

Previously researchers in the group of Professor Osbourn had assembled the early part of the pathway which makes up the scaffold structure for QS-21. However, the search for the longer full pathway, the acyl chain which forms one crucial part of the molecule that stimulates immune cells, remained unfinished.

Researchers at the John Innes Centre used a range of gene discovery approaches to identify around 70 candidate genes and transferred them to tobacco plants.

By analysing gene expression patterns and products, supported by the Metabolomic and Nuclear Magnetic Resonance (NMR) platforms at the John Innes Centre, they were able to narrow the search down to the final 20 genes and enzymes which make up the QS-21 pathway.

First author Dr Laetitia Martin said: “This is the first time QS-21 has been produced in a heterologous expression system. This means we can better understand how this molecule works and how we might address issues of scale and toxicity.”

Source: John Innes Centre