Tag: 6/2/25

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What are the Best Methods to Treat Rotator-cuff Tears?

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Photo by Kampus Production

Rotator-cuff disorders are the most common cause of shoulder symptoms. Tears of the rotator cuff can result from a substantial traumatic injury or can occur slowly over time. Most degenerative tears occur in the dominant arm of adults over the age of 40, and their prevalence increases with as you age. There are a variety of treatments.

In a recent publication in the New England Journal of Medicine, University of Michigan Health professor and chair of Physical Medicine and Rehabilitation, Nitin Jain, MD, MSPH, talks through the different treatments available for rotator-cuff tears to help bring together a better understanding of how to treat the issue for patients and providers.

Nonoperative treatment, such physical therapy, is the typical approach to treating rotator-cuff tears. However, surgery is considered in certain patients whose rotator-cuff tears don’t resolve with nonoperative treatments. Topical treatments also exist, such as glyceryl trinitrate (nitro-glycerine) gel which appears to have the greatest success.

Symptoms of rotator-cuff tears

“Patients with nontraumatic or degenerative rotator-cuff tears typically experience an onset of shoulder pain that seems to have no cause,” said Jain. 

“However, it is not uncommon for tears to be asymptomatic and become slowly painful over time, or even cause no pain at all.”

Jain says there are some activities that make the injury more painful as the tear worsens. This can include sleeping on your shoulder, overhead activities and/or lifting items above your shoulder level.

“Rotator-cuff tears may also grow over time, but there’s a lack of correlation between patient symptoms and the size and thickness of the tear,” explained Jain.

Your active range of motion and arm strength are usually affected by the tear, which gets assessed by using certain protocols when providers are searching for a diagnosis.

Rehabilitation and physical therapy for rotator-cuff tears 

This is the most common form of treatment for rotator-cuff tears, says Jain: “It is recommended that as the first line of specialist referral, patients seek care from a physical medicine and rehabilitation doctor (physiatrist) or sports medicine doctor.

“Rehabilitation and physical therapy routines address areas such as periscapular muscle weakness, correcting scapular posture and improve rotator cuff muscle strength and endurance.”

In observational studies, more than 80% of patients who received supervised physical therapy reported reduced pain and improved function between 6 months to a year. However, the trial populations consisted of patients with various types of rotator-cuff injuries and had no requirement for advanced imaging to confirm their diagnosis.

“One of the biggest factors in a successful rehabilitation was trust from patients that their physical therapy routine would improve their rotator-cuff condition,” said Jain. “The more patients leaned into the physical therapy routine, the better their outcomes were.”

Other nonpharmacologic therapies for rotator-cuff tears

Evidence suggests that psychosocial distress and depression are associated with shoulder pain and reduced function in patients with rotator-cuff tears.

“Despite this, though, there isn’t much data supporting psychosocial interventions in the treatment of rotator-cuff disorders, even though they show benefit in the treatment of other musculoskeletal disorders such as lower back pain,” said Jain.

In addition to the lack of data for psychological interventions for rotator-cuff repairs, there’s also a lack of high quality trials supporting the use of manual therapy, massage therapy, acupuncture, therapeutic ultrasonography, transcutaneous electrical nerve stimulation, shock-wave therapy or pulsed-electromagnetic-field therapy.

Topical and oral medications and injections for rotator-cuff tears

There isn’t a lot of evidence supporting the use of topical medications in treating rotator-cuff disorders. The topical treatment with the best outcomes so far has been glyceryl trinitrate.

In a small, randomised trial it showed short term benefits in the treatment of rotator-cuff disorders, but it also found there was a considerably high bias towards this treatment from participants in the study.

Topical nonsteroidal anti-inflammatory drugs such as diclofenac and ketoprofen have also been effective in providing pain relief in chronic musculoskeletal pain and tendinitis and have a better safety profile than oral, nonsteroidal anti-inflammatory drugs.

“But high quality evidence supporting their use in rotator-cuff disorders is still lacking,” explained Jain.

For oral medications, randomised research trials have shown that oral nonsteroidal anti-inflammatory drugs (NSAIDs) reduced pain, although modestly, in patients with rotator-cuff disorders. 

“Opioid drugs are generally not recommended due to risks associated with their use and lack of evidence of superiority to nonopioid therapy in a variety of musculoskeletal conditions,” said Jain.

Jain says acetaminophen hasn’t been studied specifically in rotator-cuff disorders, but what has been studied has shown little or no benefit regarding pain or function.

“Rigorous evidence is lacking to inform the use of pain-modulating drugs such as gabapentin, duloxetine, and pregabalin, specifically regarding the nonoperative treatment of rotator-cuff disorders,” said Jain.

Injection of a glucocorticoid, together with a local anaesthetic, has been reported to provide symptomatic pain relief in patients with rotator-cuff disorders.

Small trials have shown short term benefit, about four weeks long, of pain relief through using this method. The injections are performed in the subacromial space of the rotator-cuff for those with subacromial impingement syndrome. Some centres use ultrasound guidance to administer this treatment, which can reduce the risk of an inadvertent injection into the tendon.

Surgical interventions for rotator-cuff injuries

“Surgical interventions are not the initial recommendation when it comes to rotator-cuff repairs. However, they may be considered in some patients whose condition does not improve with conservative treatment,” said Jain.

Observational data supports that surgery is associated with better function and reduced pain in patients who are under 65 years of age and have smaller tears.

Surgical repairs are mostly performed arthroscopically, involving the repair of the torn tendon and resecuring it to the humerus to allow for tendon-to-bone healing as well as a low incidence of complications, explains Jain.

The hypothesis that surgical intervention can reduce the progression of muscle degradation has led some experts to recommend early surgical intervention, but data is still lacking on outcomes of early surgery compared to surgery later.

Source: Michigan Medicine – University of Michigan

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Could the Contraceptive Pill Reduce the Risk of Ovarian Cancer?

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Photo by Reproductive Health Supplies Coalition on Unsplash

It’s a little pill with big responsibilities. But despite its primary role to prevent pregnancy, the contraceptive pill (or ‘the Pill’) could also help reduce the risk of ovarian cancer, according to new research from the University of South Australia.

Screening for risk factors of ovarian cancer using artificial intelligence, UniSA researchers found that the oral contraceptive pill reduced the risk of ovarian cancer by 26% among women who had ever used the Pill, and by 43% for women who had used the Pill after the age of 45.

The study, published in the International Journal of Gynecologic Cancer, also identified some biomarkers associated with ovarian cancer risk, including several characteristics of red blood cells and certain liver enzymes in the blood, with lower body weight and shorter stature associating with a lower risk of ovarian cancer.

Researchers also found that women who had given birth to two or more children had a 39% reduced risk of developing ovarian cancer compared to those who had not had children.

UniSA researcher Dr Amanda Lumsden says understanding risks and preventative factors for ovarian cancer is key for improved treatment and outcomes.

“Ovarian cancer is notoriously diagnosed at a late stage, with about 70% of cases only identified when they are significantly advanced,” Dr Lumsden says.

“Late detection contributes to a survival rate of less than 30% over five years, in comparison to more than 90% for ovarian cancers that are caught early. That’s why it’s so important to identify risk factors.

“In this research, we found that women who had used the oral contraceptive pill had a lower risk of ovarian cancer. And those who had last used the Pill in their mid-40s, had an even lower level of risk.

“This poses the question as to whether interventions that reduce the number of ovulations could be used as a potential target for prevention strategies for ovarian cancer.”

Supported by the MRFF, the study used artificial intelligence to assess the data of 221 732 females (aged 37-73 at baseline) in the UK Biobank.

Machine learning specialist, UniSA’s Dr Iqbal Madakkatel, says the study shows how AI can help to identify risk factors that may otherwise have gone undetected.

“We included information from almost 3000 diverse characteristics related to health, medication use, diet and lifestyle, physical measures, metabolic, and hormonal factors, each measured at the start of the study,” Dr Madakkatel says.

Source: University of South Australia

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Review of Research Finds No Link between Sickle Cell Trait and Sudden Death

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Expert panel’s findings refute attribution of sudden death to sickle cell trait

Photo by National Cancer Institute on Unsplash

A systematic literature review found no evidence to support that physical exertion without rhabdomyolysis (muscle breakdown) or heat injury can cause sudden death for individuals with sickle cell trait (SCT), nor is there any high-level evidence that SCT causes acute pain crises. These results were published in the American Society of Hematology’s flagship journal, Blood, and informed the Society’s updated position statement on SCT.

“SCT has long been misunderstood, fuelling widespread misinformation and medically inaccurate claims that it can lead to sudden death. This misconception has been especially prominent in cases of Black men with SCT,” said Belinda Avalos, MD, ASH president. “In light of the pervasive, widely publicized, and harmful nature of this myth, the Society aims to further promote accurate information to protect and empower affected communities.”

Individuals with SCT have one copy of the gene associated with sickle cell disease (SCD). SCD is a blood disorder characterised by misshapen blood cells that can cause blockages, leading to infections and episodes of severe pain, often referred to as acute pain crises. Unlike SCD, SCT – which affects over 100 million people worldwide, including 8 to 10% of Black Americans – is not a disease. Individuals with SCT do not go on to develop SCD and generally do not experience any related health complications.  

“To date, this is the most authoritative and definitive systematic review on this subject,” said study author Michael R. DeBaun, MD, MPH, professor of pediatrics and medicine at Vanderbilt University School of Medicine and founder and director of the Vanderbilt-Meharry Sickle Cell Disease Center of Excellence. “This review shows that any primary, secondary, or tertiary cause of death attributable to SCT is not a diagnosis substantiated by the medical evidence.”

ASH convened an expert panel of hematologists and forensic pathologists to systematically review all existing available research to answer two primary questions: 1) Do uncomplicated acute pain crises occur in people with SCT? and 2) Can physical activity above baseline result in sudden death among those individuals?

The experts conducted a multi-database search for English-language studies on SCT and pain crises or mortality, identifying 1474 such citations. Only seven of those studies reported original data, included laboratory testing for SCT in individuals, and addressed the two primary research questions.

Of these studies, none assessed acute pain crises in individuals with SCT compared to those with SCD and only one described death in individuals reported to have SCT. This study of active-duty U.S. soldiers found only that SCT was associated with a higher risk of heat-related-exertional rhabdomyolysis, or muscle breakdown, but not a higher risk of death from any cause. After the implementation of precautions to prevent heat and environmental-related injury in military personnel, the race-adjusted risk of death was no different in individuals with SCT compared to individuals without SCT.

“In the absence of two medical conditions that we are all at risk for, exertional rhabdomyolysis or crush injuries leading to rhabdomyolysis, individuals with SCT are not susceptible to sudden death. Even under these extreme environmental conditions, unexplained sudden death cannot be attributed to SCT,” said Dr. DeBaun. Taken together, these findings demonstrate that “in individuals with SCT, the likelihood of SCT alone or pain crises being the root cause of sudden death is medically impossible,” he added.

While conducting this systematic review, the experts found several studies in which the presence of sickled blood cells at autopsy was cited as evidence of death by acute pain crisis in individuals with SCT. However, the experts did not find any studies that had human data to support this hypothesis, nor any clinical descriptions sufficient to make a diagnosis of an acute pain crisis immediately preceding death.

“Medicine, even in the post-mortem setting, is science,” said corresponding study author Lachelle D. Weeks, MD, PhD, assistant professor of medicine at Harvard Medical School and physician-scientist in the division of population sciences at Dana-Farber Cancer Institute. “Our diagnoses have to make sense and be backed by medical evidence. Given the findings of this study, we owe it to individuals with SCT to ensure that post-mortem examinations check for evidence of rhabdomyolysis and other medical or traumatic causes of death.”

The review had some limitations, most notably a lack of high quality, peer-reviewed direct evidence. To help mitigate this challenge, panel members were encouraged to consider indirect evidence when reviewing abstracts and judged evidence certainty following the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) framework. However, given this paucity of data, the experts hope this review prompts additional SCT research.

Following the results of this study, ASH revised its position statement on SCT, which states that listing “sickle cell crisis” or “sickle cell trait” as a cause of death on an autopsy report for an individual with sickle cell trait is medically inaccurate and without medical evidence of causation. To read the updated statement and learn more about ASH’s advocacy efforts in this area, visit https://hematology.org/advocacy.

Source: American Society of Hematology

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Why Antibiotics can Fail Even against Non-resistant Bacteria

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Drug-resistant Salmonella. Credit: CDC

Antibiotics are indispensable for treating bacterial infections. But why are they sometimes ineffective, even when the bacteria are not resistant? In their latest study published in the journal Nature, researchers from the University of Basel challenge the conventional view that a small subset of particularly resilient bacteria are responsible for the failure of antibiotic therapies.

In certain infectious diseases caused by bacteria, antibiotics are less effective than expected. One example is infections caused by Salmonella bacteria, which can lead to illnesses such as typhoid fever. For many years, researchers believed that a small subset of dormant bacteria are the main problem in fighting infections. These so-called persisters can survive antibiotic treatment and cause relapses later. Researchers worldwide have been working on new therapies aimed at targeting and eliminating these “sleeping” bacteria.

In a new study, Professor Dirk Bumann’s team from the Biozentrum of the University of Basel challenges the prevailing concept that persisters are the cause of antibiotic ineffectiveness. “Contrary to widespread belief, antibiotic failure is not caused by a small subset of persisters. In fact, the majority of Salmonella in infected tissues are difficult to kill,” explains Bumann. “We have been able to demonstrate that standard laboratory tests of antimicrobial clearance produce misleading results, giving a false impression of a small group of particularly resilient persisters.”

Nutrient starvation increases Salmonella resilience

The researchers investigated antimicrobial clearance in both Salmonella-infected mice and tissue-mimicking laboratory models. The body’s defense mechanisms against bacteria often include reducing the availability of nutrients. The researchers have now revealed that in fact, this nutrient starvation is the main reason for Salmonella bacteria surviving treatments with antibiotics. The researchers assume that the same applies to other bacterial pathogens.

“Under nutrient-scarce conditions, bacteria grow very slowly,” says Bumann. “This may seem good at first, but is actually a problem because most antibiotics only gradually kill slowly growing bacteria.” As a result, the drugs are much less effective, and relapses can occur even after prolonged therapy.

Real-time analyses reveal misconception

The scientists used an innovative method to monitor antibiotic action in single bacteria in real time. “We demonstrated that nearly the entire Salmonella population survives antibiotic treatment for extended periods, not just a small subset of hyper-resilient persisters,” says first author Dr Joseph Fanous.

A major issue with the standard methods used worldwide for decades is their indirect and delayed measurement of bacterial survival, leading to distorted results. “Traditional tests underestimate the number of surviving bacteria,” explains Fanous. “And they falsely suggest the presence of hyper-resilient subsets of persisters that do not actually exist.” This misinterpretation has influenced research for many years.

Novel tools for antibiotics research

These findings could fundamentally change antibiotics research. “Our work underlines the importance of studying bacterial behaviour and antibiotic effects live and under physiologically relevant conditions,” emphasises Bumann. “In a few years, modern methods like real-time single-cell analysis will hopefully become standard.” Shifting the focus from persisters to the impact of nutrient starvation is an important step toward more effective therapies against difficult-to-treat infections.

The project is part of the National Center of Competence in Research (NCCR) “AntiResist”. The research consortium aims to develop innovative strategies to combat bacterial infections. Dirk Bumann is one of the directors of the NCCR “AntiResist”.

Source: University of Basel

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Could the Key to IBS Treatment Lie in the Brain?

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

Although irritable bowel syndrome (IBS) affects about a tenth of the global population, the underlying causes and mechanisms of IBS remain unclear and thus treatments focus on symptom management. At Tokyo University of Science (TUS), Japan, Professor Akiyoshi Saitoh and his research group have spent the past decade exploring this topic. This study, published in the British Journal of Pharmacology, discovered that a class of drugs called opioid delta-receptor (DOP) agonists may help alleviate IBS symptoms by targeting the central nervous system rather than acting directly on the intestine.

One of the main motivations for this study was the growing evidence linking IBS closely to psychological stress. Saitoh’s group aimed to address this potential root cause by focusing on finding a novel animal model for this condition. In a 2022 study, they developed a mice model repeatedly exposed to psychological stress – using a method called chronic vicarious social defeat stress (cVSDS) – which developed symptoms similar to a type of IBS called IBS-D. These symptoms included overly active intestines and heightened sensitivity to abdominal pain, even though their organs showed no physical damage. The cVSDS animal model involved having the subject mouse repeatedly witness a territorial, aggressive mouse defeating a cage mate, inducing indirect chronic stress.

Using the cVSDS model, the researchers sought to determine whether DOP in the brain, which is closely linked to pain and mood regulation, could serve as promising drug targets for treating stress-induced IBS. To achieve this, they performed a series of detailed experiments to observe the effects of DOP agonists on IBS symptoms and chemical signaling in the brain. Some experiments involved measuring the speed of a charcoal meal through the intestine to assess gastrointestinal motility and evaluate the impact of stress or treatments on bowel movement speed, along with directly measuring neurotransmitter concentrations using in vivo brain microdialysis. This revealed that re-exposure to VSDS increased glutamate levels in the insular cortex, but these elevated levels were normalised with DOP agonists.

According to the results, the administration of DOP agonists helped relieve abdominal pain and regulated bowel movements in cVSDS mice. Interestingly, applying the DOP agonists directly to a specific brain region called the insular cortex had similar effects on IBS symptoms as systemic treatment. “Our findings demonstrated that DOP agonists acted directly on the central nervous system to improve diarrhoea-predominant IBS symptoms in mice, and suggest that the mechanism of action involves the regulation of glutamate neurotransmission in the insular cortex,” highlights Saitoh.

Taken together, the continued research by Saitoh’s group on this topic could pave the way for effective treatments for IBS. “DOP agonists could represent a groundbreaking new IBS treatment that not only improves IBS-like symptoms but also provides anti-stress and emotional regulation effects. In the future, we would like to conduct clinical developments with the goal of expanding the indication of DOP agonists for IBS, in addition to depression,” remarks Saitoh.

Compared to currently available IBS treatments, such as laxatives, antidiarrhoeals, analgesics, and antispasmodics, targeting the underlying stress with DOP agonists may offer a more definitive solution with minimal adverse effects. Further clarification of the roles of stress and brain chemistry in the development of IBS will be essential in achieving this much-needed medical breakthrough. With promising prospects, future studies will translate Saitoh’s group’s findings to humans, bringing great relief to those affected by IBS.

Source: Tokyo University of Science