Some individuals who have had anterior-cruciate-ligament reconstruction (ACLR), the kind of surgery often performed on athletes’ knees, may develop early-onset knee osteoarthritis. A new study in the Journal of Orthopaedic Research indicates that altered knee joint movement after ACLR could be a contributing factor.
The study used a unique dynamic X-ray imaging system to accurately measure knee joint movement during walking in people who had undergone ACLR surgery and those with healthy knees. Compared with healthy controls, ACLR patients had a higher vertical position of the patella and a higher location of articular contact between the patella and the femur. A higher riding patella in the ACLR patients was caused by a longer-than-normal patellar tendon, the structure connecting the patella to the tibia. A surprising finding was that a higher riding patella was observed in both the ACLR knee and the uninjured contralateral knee of the ACLR patients.
Investigators suspect that a higher riding patella may contribute to the development of knee osteoarthritis by shifting the load bearing areas between the patella and the femur to regions of cartilage unaccustomed to load and leaving previously loaded regions unloaded.
“We don’t know whether a longer-than-normal patellar tendon that resulted in a higher riding patella existed prior to the ACL injury or resulted from the ACL injury or ACLR surgery. Further research is needed to determine the cause of a longer-than-normal patellar tendon in individuals who have undergone ACLR surgery,” said corresponding author Marcus G. Pandy, PhD, MEngSc, of the University of Melbourne, in Australia.
A multicentre study led from Finland has shown that lymph node transfer is a viable treatment for the swelling in the affected limb, a condition known as lymphoedema, after breast cancer surgery. Unfortunately, a drug to improve the outcomes of the transfer treatment was not shown to be effective.
“I am becoming increasingly convinced that lymphoedema is not just a lymphatic problem, but is connected to an immunological factor,” says Plastic Surgeon and InFLAMES Flagship Researcher Pauliina Hartiala from the University of Turku in Finland.
Around one in four women with breast cancer undergo an axillary lymph node removal surgery. The surgery is performed if tests show that the cancer has spread from the breast tissue to the lymph nodes and is often followed by radiotherapy.
After the treatment, around 20–40% of women develop lymphoedema, a lymphatic drainage disorder in the affected arm. In 2022, about 2.3 million women were diagnosed with breast cancer worldwide. In men, the disease is rare.
Swelling can start years after treatment
“Lymphedema usually starts about six months after cancer surgery, but can also occur with a delay of several years after the cancer has been treated,” says Pauliina Hartiala.
In lymphedema, fluid accumulates in the tissue at first, but over time fat and firm connective tissue also begin to accumulate in the arm. Eventually, the upper limb becomes thick and clumsy. An elastic compression sleeve is used to try to control the problem by applying pressure to prevent the limb from swelling. However, the swelling can become so severe that the arm clearly interferes with everyday life, both at work and at leisure.
Lymphedema can be treated with surgical options including liposuction, lymphatic bypass procedure, or lymph node transfer. In the transfer surgery, the patient’s lymph nodes are transferred from the groin area to the armpit, or axilla, to replace the removed lymph nodes. The procedure involves extensive scar removal from the armpit.
Lymph node transfer is often performed at the same time as the breast operated on for cancer is reconstructed with a tissue flap taken from the patient’s abdomen.
A lymph node transfer involves removing lymph nodes from the groin area and transferring them into the armpit. Image: Pauliina Hartiala
Additional benefits were expected from a growth factor
Pauliina Hartiala was one of the leaders of a multicentre study in Turku, Finland, focused on investigating whether the outcome of lymph node transfer could be improved by a growth factor, a drug called Lymfactin, that promotes growth and repair of lymphatic vessels. The study was carried out in five research centres in Finland and Sweden and builds on extensive basic research led by Finnish Professors Kari Alitalo, Seppo Ylä-Herttuala and Anne Saarikko. Lymfactin is a research product from the Finnish pharmaceutical company Herantis Pharma.
The study tested whether the growth factor could improve lymph node flap function compared to a lymph node transfer conducted without the drug. The study involved 39 women. Of these, 20 underwent a transfer procedure where the tissue flap was injected with the lymphatic growth factor before it was transferred. For the second group, the transfer was carried out by adding only saline (placebo) to the tissue flap.
“Even though the drug therapy had worked well in combination with lymph node transfer in the animal model, it did not provide sufficient additional benefit to surgery in humans,” says Pauliina Hartiala.
Although Lymfactin did not work as expected in humans, Pauliina Hartiala is pleased with the other results of the study. In both study groups, the excess arm volume reduced during follow-up. In addition, the patients treated with Lymfactin had a significantly greater reduction in skin interstitial fluid than the placebo group.
“We are the first to show, with a double-blind study, that lymph node transfer is a viable treatment for some patients with lymphoedema after breast cancer surgery. One of the results of our study was the fact that the operation significantly improved women’s quality of life, which is an important finding.”
Pauliina Hartiala works as a Plastic Surgeon at Turku University Hospital, alongside her research work. She now believes that besides a lymphatic problem, lymphedema is linked to an immunological factor. It may be one or more of the immune cells that are involved in the accumulation of connective tissue and fat in the lymphoedema.
“If this is the case, further research will allow us to investigate whether regulating the functions of this cell population could reduce fat accumulation in the limb,” concludes Hartiala.
Researchers grow cartilage replacements from cells of the nasal septum to repair cartilage injuries in the knee. (Photo: University of Basel, Christian Flierl)
An unlucky fall while skiing or playing football can spell the end of sports activities. Damage to articular cartilage does not heal by itself and increases the risk of osteoarthritis. Researchers at the University of Basel and the University Hospital Basel have now shown that even complex cartilage injuries can be repaired with replacement cartilage engineered from cells taken from the nasal septum.
A team at the Department of Biomedicine led by Professor Ivan Martin, Dr Marcus Mumme and Professor Andrea Barbero has been developing this method for several years. It involves extracting the cells from a tiny piece of the patient’s nasal septum cartilage and then allowing them to multiply in the laboratory on a scaffold made of soft fibres. Finally, the newly grown cartilage is cut into the required shape and implanted into the knee joint.
Earlier studies have already shown promising results. “Nasal septum cartilage cells have particular characteristics that are ideally suited to cartilage regeneration,” explains Professor Martin. For example, it has emerged that these cells can counteract inflammation in the joints.
More mature cartilage shows better results
In a clinical trial involving 98 participants at clinics in four countries, the researchers compared two experimental approaches. One group received cartilage grafts that had matured in the lab for only two days before implantation – similar to other cartilage replacement products. For the other group, the grafts were allowed to mature for two weeks. During this time, the tissue acquires characteristics similar to native cartilage.
For 24 months after the procedure, the participants self-assessed their well-being and the functionality of the treated knee through questionnaires. The results, published in the scientific journal Science Translational Medicine, showed a clear improvement in both groups. However, patients who received more mature engineered cartilage continued to improve even in the second year following the procedure, overtaking the group with less mature cartilage grafts.
Magnetic resonance imaging (MRI) further revealed that the more mature cartilage grafts resulted in better tissue composition at the site of the implant, and even of the neighbouring cartilage. “The longer period of prior maturation is worthwhile,” emphasizes Anke Wixmerten, co-lead author of the study. The additional maturation time of the implant, she points out, only requires a slight increase in effort and manufacturing costs, and gives much better results.
Particularly suited to larger and more complex cartilage injuries
“It is noteworthy that patients with larger injuries benefit from cartilage grafts with longer prior maturation periods,” says Professor Barbero. This also applies, he says, to cases in which previous cartilage treatments with other techniques have been unsuccessful.
“Our study did not include a direct comparison with current treatments,” admits Professor Martin. “However, if we look at the results from standard questionnaires, patients treated with our approach achieved far higher long-term scores in joint functionality and quality of life.”
Based on these and earlier findings, the researchers now plan to test this method for treating osteoarthritis – an inflammatory disease that causes joint cartilage degeneration, resulting in chronic pain and disability.
Two large-scale clinical studies, funded by the Swiss National Science Foundation and the EU research framework programme Horizon Europe, are about to begin. These studies will explore the technique’s effectiveness in treating a specific form of osteoarthritis affecting the kneecaps (ie, patellofemoral osteoarthritis). The activities will further develop in Basel the field of cellular therapies, strategically defined as a priority area for research and innovation at the University of Basel and University Hospital Basel.
A novel tool for rapidly identifying the genetic “fingerprints” of cancer cells may enable future surgeons to more accurately remove brain tumours while a patient is in the operating room, new research reveals. Many cancer types can be identified by certain mutations, changes in the instructions encoded in the DNA of the abnormal cells.
Led by a research team from NYU Langone Health, the new study describes the development of Ultra-Rapid droplet digital PCR, or UR-ddPCR, which the team found can measure the level of tumour cells in a tissue sample in only 15 minutes while also being able to detect small numbers of cancer cells (as few as five cells/mm2).
The researchers say their tool is fast and accurate enough, at least in initial tests on brain tissue samples, to become the first practical tool of its kind for detecting cancer cells directly using mutations in real time during brain surgery.
The researchers showed that UR-ddPCR had markedly faster processing speed than standard droplet digital polymerase chain reaction (ddPCR). Standard ddPCR can accurately quantify tumor cells, but it typically takes several hours to produce a result, making it impractical as a surgical guide.
“For many cancers, such as tumors in the brain, the success of cancer surgery and preventing the cancer’s return is predicated on removing as much of the tumor and surrounding cancer cells as is safely possible,” said study co-senior study investigator and neurosurgeon Daniel A. Orringer, MD.
“With Ultra-Rapid droplet digital PCR, surgeons may now be able to determine what cells are cancerous and how many of these cancer cells are present in any particular tissue region at a level of accuracy that has never before been possible,” said Dr Orringer.
Published in the journal Med, the study showed that UR-ddPCR produced the same results as standard ddPCR and genetic sequencing in more than 75 tissue samples from 22 patients at NYU Langone undergoing surgery to remove glioma tumours. Results from UR-ddPCR were also checked against known samples with cancer cells and samples without any cancer.
“Our study shows that Ultra-Rapid droplet digital PCR could be a fast and efficient tool for making a molecular diagnosis during surgery for brain cancer, and it has potential to also be used for cancers outside the brain,” said senior study investigator Gilad Evrony, MD, PhD.
To develop UR-ddPCR, researchers looked for efficiencies in each of the steps involved in standard ddPCR. The team shortened the time needed to extract DNA from tumour samples from 30 minutes to less than 5 minutes in a manner that is still compatible with subsequent ddPCR. The researchers also found efficiencies by increasing the concentrations of the chemicals used in testing, reducing the overall time needed for some steps from two hours to less than three minutes. Time savings were also achieved by using reaction vessels prewarmed to each of the two temperatures required by the PCR rather than repeatedly cycling the temperature of a single reaction vessel between two temperatures.
For the study, researchers used UR-ddPCR to measure the levels of two genetic mutations, IDH1 R132H and BRAF V600E, which are prevalent in brain cancers. They combined UR-ddPCR with another technique the researchers developed earlier, called stimulated Raman histology, to calculate both the fraction and the density of tumour cells within each tissue sample.
Researchers caution that widespread use of the tool awaits further refinements and clinical trials. They say their next step is to automate UR-ddPCR to make it faster and simpler to use in the operating room. Subsequent clinical trials will be necessary to compare patient outcomes using their tool compared to current diagnostic technologies. They also plan to develop the technology to identify other common genetic mutations for other cancer types.
A mathematical modelling study conducted in Germany suggests that ovarian cancer incidence could be reduced and healthcare savings boosted if women who have already completed their families were offered fallopian tube removal during any other suitable abdominal surgeries. Angela Kather and Ingo Runnebaum of Jena University Hospital, Germany, and colleagues present these findings on January 30th in the open-access journal PLOS Medicine.
Some of the most widespread and serious forms of ovarian cancer begin in the fallopian tubes, and removing them may reduce ovarian cancer risk. While women at average risk of ovarian cancer are not recommended to have surgery solely to remove their fallopian tubes, many surgeons offer “opportunistic” tube removal during other gynaecologic surgeries such as hysterectomy or tubal sterilisation. Opportunistic removal may also be feasible during other abdominal surgeries, such as gallbladder removal.
However, the overall potential benefits of opportunistic fallopian tube removal have been unclear. To help clarify, Kather and colleagues developed a mathematical model that incorporates real-world patient statistics to predict population-level risks of ovarian cancer after opportunistic fallopian tube removal, as well as the potential healthcare cost savings.
By applying the model to statistics from Germany, the researchers predicted that opportunistic fallopian tube removal during every hysterectomy and tubal sterilisation could reduce ovarian cancer cases by 5% across the female population of Germany. Removal during every suitable abdominal surgery for women who are done having children could reduce nationwide cancer cases by 15%, the analysis suggests, and it could save more than €10 million in healthcare costs annually.
Ovarian cancer is the third most common gynaecologic cancer in the world and has a mortality rate of 66%. Overall, these findings suggest that opportunistic fallopian tube removal during appropriate abdominal surgeries could not only lower population-level ovarian cancer risks and prevent ovarian cancer deaths, but also provide economic benefits. This study could help inform health policy and insurance costs for the procedure.
The authors add, “We developed a mathematical model to estimate the likelihood of women undergoing surgeries that offer an opportunity for fallopian tube removal and the potential for reducing their ovarian cancer risk. Applying this model to the entire female population of Germany revealed that 15% of ovarian cancer cases could be prevented if fallopian tubes were removed during every suitable abdominal surgery in women who have completed their families. This approach has the potential to extend healthy years of life and significantly save healthcare costs.”
For people with an injured anterior cruciate ligament (ACL) in the knee, surgical ACL reconstruction (ACLR) is an effective treatment for restoring joint stability, however, many treated patients still develop additional long-term knee problems, such as knee osteoarthritis. New research published in the Journal of Orthopaedic Research reveals that individuals exhibit an altered gait after ACLR, which can contribute to these problems.
For the study, investigators compared gait biomechanics between the ACLR and uninjured limbs of 58 patients who underwent ACLR and 58 uninjured control individuals.
Although gait biomechanics became more symmetrical in patients with ACLR over the first 12 months post‐ACLR, the ACLR and uninvolved limbs demonstrated persistent aberrant gait biomechanics compared with the uninjured control individuals.
“A persistent aberrant gait pattern following ACLR, like that observed in our study, can induce joint loads that may contribute to further long-term knee joint problems,” said corresponding author Christin Büttner, MS, of the University of North Carolina at Chapel Hill. Implementing early rehabilitative measures to normalise gait following ACLR could help to maintain long-term knee joint health in both the injured and uninjured limb.”
Obesity and type 2 diabetes are risk factors for various malignancies, including pancreatic cancer, which has a high death rate. A new analysis in Diabetes/Metabolism Research and Reviews suggests that metabolic-bariatric surgery may lower the risk of developing pancreatic cancer in people with obesity, especially in those who also have type 2 diabetes.
In the systematic review and meta-analysis, investigators identified 12 relevant studies that explored the effects of metabolic-bariatric surgery on pancreatic cancer incidence, with a total of 3 711 243 adults with obesity. Surgery was associated with a 44% reduction in pancreatic cancer risk among individuals with obesity but without type 2 diabetes and a 79% risk reduction in those with both obesity and type 2 diabetes.
“Metabolic-bariatric surgery not only has beneficial effects on obesity and type 2 diabetes but also may play a crucial role in reducing the risk of pancreatic cancer in these individuals,” said corresponding author Angeliki M. Angelidi, PhD, of the Broad Institute of MIT and Harvard. “These findings underscore the need for further research to elucidate the underlying mechanisms and understand the full spectrum of health benefits of metabolic-bariatric surgery beyond weight loss.”
Fluorescein angiography capable of assessing neural blood flow in chronic nerve compression neuropathy
Fluorescein-enhanced contrast imaging shows a rabbit’s normal sciatic nerve, left, and a damaged one. Credit: Osaka Metropolitan University
In the modern office, it’s a daily struggle against the onset of carpal tunnel syndrome. The worst case could mean needing surgery to alleviate compression of the nerves or to repair damaged nerves. Helping surgeons visually check the areas where neural blood flow has decreased due to chronic nerve compression can lead to improvements in diagnostic accuracy, severity assessments, and outcome predictions.
With this in mind, an Osaka Metropolitan University-led research team involving Graduate School of Medicine student Kosuke Saito and Associate Professor Mitsuhiro Okada investigated the use of fluorescein angiography, a method employed in neurosurgery and ophthalmology to highlight blood vessels, to visualise neural blood flow in chronic nerve compression neuropathies like carpal tunnel syndrome. The findings were published in Neurology International.
The team found that fluorescein angiography could detect a decrease in neural blood flow in rats and rabbits with chronic nerve compression neuropathy. The results also correlated with electrodiagnostic findings.
Then fluorescein angiography was used for human patients undergoing open carpal tunnel release surgery, and the data also correlated strongly with electrodiagnostic testing. The findings indicate that fluorescein angiography might possess high diagnostic capabilities to assess neural blood flow during surgery.
“In surgery for severe chronic nerve compression neuropathy, the surgeon’s experience plays a big role in judging whether the surgical range is appropriate or whether additional treatment is necessary,” graduate student Saito noted. “This research has shown that fluorescein angiography can visualise impaired areas and assess the impairment severity, so we believe that it has the potential to contribute to improving accuracy for related surgeries.”
Discoid lateral meniscus and osteochondritis dissecans in adolescent patients. The black arrow represents DLM and the white arrow represents osteochondritis dissecans. Credit: Osaka Metropolitan University
Growing pains are common in maturing children, but sometimes this growth can be irregular and cause injury. Discoid lateral meniscus (DLM), a misshapen knee cartilage, is one such occurrence that can degenerate into osteochondritis dissecans, a joint disorder where the bone and joint begin to separate from the rest of the bones. It has been reported that osteochondritis dissecans of the femoral condyle occurs in approximately 14.5% of cases of DLM, but there has been little analysis of its treatment to date.
Dr Ken Iida and Specially Appointed Professor Yusuke Hashimoto’s team at Osaka Metropolitan University’s Graduate School of Medicine analysed the incidence of post-surgery osteochondritis dissecans. This analysis consisted of two groups, a pre-osteochondritis group with DLM and osteochondritis dissecans of the outer femoral epicondyle, and a non-osteochondritis dissecans DLM group. They studied 95 cases of DLM patients under the age of 15 who underwent surgery between 2003 and 2017 and had five years of post-surgery records. There were 15 cases in the pre-osteochondritis dissecans group and 80 non-osteochondritis dissecans cases.
Their analysis found that the surgical results for osteochondritis dissecans were good in pre-osteochondritis cases, but 28.5% had a recurrence of the joint disorder. In the non-osteochondritis dissecans group, 8.8% were diagnosed with the disorder after surgery. Additionally, age was found to be a risk factor for relapse or post-surgical osteochondritis dissecans, and surgery on patients ages 9 and under was also involved in the occurrence of osteochondritis dissecans.
“Patients with DLM accompanied by osteochondritis dissecans of the femoral condyle often have difficulty in deciding on a treatment method,” Dr Iida explained. “Based on the results of this study, we believe for patients ages 9 years or younger, it is necessary to consider conservative treatment methods rather than immediate surgery.”
A UCLA research team has created the Comorbid Operative Risk Evaluation (CORE) score to better account for the role chronic illness plays in patient’s risk of mortality after operation, allowing surgeons to adjust to patients’ pre-existing conditions and more easily determine mortality risk.
For almost 40 years, researchers have used two tools, the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI), to measure the impact of existing health conditions on patient outcomes. These tools use ICD codes that are input by medical professionals and billers to account for patient illness. These tools, however, were not designed for patients undergoing surgery and often address chronic illnesses that are not relevant to surgical populations. They often capture data from medical billing records and lack nuanced information regarding pre-existing health conditions.
A total of 699 155 patients were used to develop the model, of which 139 831 (20%) comprised the testing cohort. The researchers queried adults undergoing 62 operations across 14 specialties from the 2019 National Inpatient Sample (NIS) using International Classification of Diseases, 10th Revision (ICD-10) codes. They sorted ICD-10 codes for chronic diseases into Clinical Classifications Software Refined (CCSR) groups. They used logistic regression on CCSR with non-zero feature importance across four machine learning algorithms predicting in-hospital mortality, and used the resultant coefficients to calculate the Comorbid Operative Risk Evaluation (CORE) score based on previously validated methodology. The final score ranges from zero, representing lowest risk, to 100, which represents highest risk.
Impact
Health services and outcomes research using retrospective databases continues to represent a growing proportion of surgical research. Researchers highlighting quality issues and disparities are well-intentioned. However, without appropriate tools, it can be unclear if poor outcomes are independent of pre-existing conditions.
“The advent of novel statistical software and methodology have enabled researchers to exploit large databases to answer questions of healthcare quality, disparities, and outcomes,” said Dr Nikhil Chervu, a resident physician in the UCLA Department of Surgery and the study’s lead author. “These databases, however, often capture data from medical billing records and lack nuanced information regarding pre-existing health conditions. Without addressing differences in patients’ chronic illnesses, population comparisons may fall flat. Incorporation of this score in additional research will further validate its use and help improve analysis of surgical outcomes using large databases.”
