The growing resistance of bacteria to antibiotics worries doctors and researchers around the world. Now, an international study led by a team at Hadassah-University Medical Center and the Faculty of Dental Medicine of the Hebrew University of Jerusalem shows the potential effectiveness of PASA16 bacteriophage therapy in coping with dangerous Pseudomonas aeruginosa infections.

The study paves the way for future clinical trials and encourages further exploration of phage therapy as an alternative and auxiliary approach against antibiotic-resistant infections, the authors suggested.

Ran Nir-Paz, an associate professor of clinical microbiology and infectious diseases at Hadassah, who also works at Hebrew University and Hadassah’s Israeli Phage Therapy Center, and Dr. Ronen Hazan, from the bioresearch institute at the university’s dental school, headed the team that published the study in the journal Clinical Advances. It was entitled “Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate-use case series.”

How can viruses be used to help where antibiotics can't?

The use of specific antibacterial viruses against infections has aroused much attention as a critical addition to conventional antibiotics, although there have been few clinical trials to test phages on patients. This was the largest study of its kind, and so far it has produced an impressive 86.6% success rate.

Pseudomonas aeruginosa is a bacteria found in the environment – in soil, water, and plants – and as part of bacteria in humans. It is both a pathogen and opportunistic bacteria, causing infections in patients with weakened immune systems or underlying chronic illnesses.

Before the treatment began, all Pseudomonas aeruginosa samples from patients were tested, and treatment was personalized in those who were found to be sensitive to the PASA16 phage.

During the PASA16 phage treatment, only minor and manageable side effects were observed. Remarkably, 13 out of 15 patients with available data had a favorable clinical outcome. The duration of treatment spanned from eight days to six weeks, with one- to twice-daily regimen

This highlights the potential of combining PASA16 phage with antibiotics as a promising approach for patients with previously unsuccessful treatments.

“We are elated by the promising results of our study using phage PASA16 to treat tough Pseudomonas aeruginosa infections,” wrote the Israeli researchers, who were joined by colleagues in Israel, the US, and Australia. “This groundbreaking research offers hope for patients with persistent infections and highlights the potential of phage therapy as a valuable alternative to conventional antibiotics in combating antibiotic-resistant pathogens.”

Bacteriophage, also called phage or bacterial virus, belong to a group of viruses that infect bacteria. They were discovered independently by Frederick Twort in Great Britain in 1915 and Félix d’Hérelle in France in 1917. D’Hérelle coined the term bacteriophage, meaning “bacteria eater,” to describe the agent’s ability to destroy bacteria.

Thousands of varieties of phages exist, each of which may infect only one type or a few types of bacteria. Like all viruses, phages are simple organisms that consist of a core of genetic material (nucleic acid) surrounded by a protein capsid. The nucleic acid may be either DNA or RNA and may be double-stranded or single-stranded.

Phages have been used since the late 20th century as an alternative to antibiotics in the former Soviet Union and Central Europe, as well as in France. They are regarded as a possible therapy against multi-drug-resistant strains of many bacteria.

The authors said their work highlighted the potential of combining PASA16 phage with antibiotics as a promising approach for patients with previously unsuccessful treatments.

“By outlining potential clinical protocols, this study paves the way for future trials,” they wrote. “The success observed encourages further research and exploration of phage therapy as an alternative and complementary approach to combat antibiotic-resistant infections.”

These bacterial infections can range from mild to severe, affecting various body parts, including the lungs, urinary tract, skin, and wounds. It is a common cause of hospital-acquired infections, particularly in patients with weak immune systems or those using mechanical ventilation or invasive devices.

The pathogen’s ability to form protective biofilms hinders treatment, sometimes necessitating the combination of antibiotics and alternative therapies such as phage therapy. Strict infection-control measures in healthcare facilities are essential to combat its persistence.

The phage, which was provided pro bono by the US phage company Adaptive Phage Therapeutics, was given using various methods, including intravenous, local application to the infection site, and topical use.

Link to the publication: www.jpost.com

Pulmonary embolism (PE) is currently the third leading cause of death from heart disease after myocardial infarction (heart attacks) and stroke. Early diagnosis is essential as a staggering one in three deaths occur within the first few hours compared with only 7% of deaths in properly diagnosed and treated cases.

Catheter-directed thrombolysis (CDT) is a procedure that involves delivering low doses of medication directly into the pulmonary arteries using a catheter. However, due to the lack of comprehensive research on its safety and efficacy, treatment guidelines for CDT vary because of this uncertainty.

In a comparative analysis of different treatments for pulmonary embolisms, Israeli researchers have made a significant breakthrough. The study found that CDT was associated with a 55% decreased risk of death as well as lower risks of major bleeding and brain bleeds among 65%, when compared to other treatment options.

Dr. Bruria Hirsh Raccah, Clinical pharmacist in the cardiology department at the Hadassah Medical Center and researcher at the Hebrew University of Jerusalem and a co-author of the study, cautions that "further research is necessary before drawing definitive conclusions. However, the findings indicate that CDT should be considered the preferred treatment among eligible patients, given its safety and effectiveness, especially when compared to the higher toxicity of systemic thrombolysis.”

“Although this study should be interpreted as hypothesis generating, our findings suggest that, among patients eligible for CDT and where facilities exist, CDT should be the preferred treatment, given its safety and effectiveness, and given the higher toxicity of systemic thrombolysis” writes Dr. Bruria Hirsh Raccah, a researcher at the Hebrew University of Jerusalem, Jerusalem, Israel, with coauthors.

The study was part of Stav Yanko’s dissertation at the Hebrew University of Jerusalem.

The study was co-authored by Bruria Hirsch Raccah, Stav Yanko and other researchers from Hadassah Medical Center.

“Mortality and safety assessment of catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate or high-risk pulmonary embolism: systematic review and network meta-analysis” was published June 19, 2023. https://www.medscape.com/viewarticle/993506?src=

A new study found that brain stimulation combined with cognitive training can improve symptoms of ADHD.

“ADHD is one of the most common neurodevelopmental disorders affecting children across the world,” Ornella Dakwar-Kawar, a post-doctoral researcher at the Hebrew University of Jerusalem, said in a press release. “Treating the condition with medication improves a child’s attention span and overall mood, however … there can be side effects including headache and a loss of appetite,” Dakwar-Kawar added. “There is, therefore, a pressing need for developing and testing novel, non-pharmacological interventions for ADHD.”

ADHD symptoms include trouble paying attention, overactivity, and impulsive behaviors, according to the Centers for Disease Control and Prevention. The CDC estimates that 6 million children in the US ages 3 to 17 have been diagnosed with ADHD. The condition is usually treated with a combination of behavior therapy and medication. Researchers at the University of Surrey and the Hebrew University conducted a clinical trial with 23 children ages 6 to 12 who were unmedicated. The researchers administered a non-invasive brain stimulation with a mild electrical current running through two electrodes. Cognitive treatment included problem-solving and reading comprehension. After two weeks, 55% of the children showed significant clinical improvements in their ADHD symptoms, as reported by their parents, in comparison to 17% of children in the control group who received placebo brain stimulation. The improvements were maintained at three weeks post-trial, with 64% reporting positive effects from the treatment compared to 33% in the control group. The study, published in the journal Translational Psychiatry, also found that participants had changes in their brain electrical activity patterns, even three weeks after treatment. “I believe that the scientific community is duty-bound to investigate and develop ever more effective and longer-lasting treatments for ADHD,” said Roi Cohen Kadosh, co-lead of the study and professor of cognitive neuroscience at the University of Surrey.

“The findings we demonstrate in our study suggest that a combination of transcranial direct current stimulation (tRNS), which is shown to be safe with minimal side effects, has the potential to transform the lives of children and their families,” Kadosh added. “The results from this proof-of-concept study, together with previous results we received using tRNS, increase our confidence that in the future non-invasive brain stimulation may be able to provide an alternative to medication as a treatment pathway for children,” Kadosh continued. “However, our important test will be the results from a multi-center clinical trial with a larger sample that we will start soon.” Scientists noted that further research and trials would need to be done to make brain stimulation a practical therapy for children with ADHD.

“This is an important first step in offering new therapeutic options for ADHD. Future studies, with larger and more varied samples, should help establish this as a viable therapy for ADHD, and help us understand the underlying mechanisms of the disorder,” said Dr. Mor Nahum, co-lead of the study and head of the Computerized Neurotherapy Lab at the Hebrew University.“If the results will be replicated in future larger studies we will be able to offer a novel, promising non-invasive, and safe treatment to large number of children and their families not only in the field of ADHD but in other neurodevelopmental disorders,” said professor Itai Berger, co-lead of the study.

Link to the publication: nypost.com