Intermittent fasting protects against liver inflammation and liver cancer, claims study

Fatty liver disease often leads to chronic liver inflammation and can even result in liver cancer. Scientists from the German Cancer Research Center (DKFZ) and the University of Tübingen have now shown in mice* that intermittent fasting on a 5:2 schedule can halt this development. The fasting regime reduces the development of liver cancer in mice with pre-existing liver inflammation. The researchers identified two proteins in liver cells that are jointly responsible for the protective effect of fasting. An approved drug can partially mimic this effect.

The most common chronic liver condition is non-alcoholic fatty liver disease. It can have serious consequences: If left untreated, it can lead to liver inflammation (metabolic dysfunction-associated steatohepatitis, MASH), liver cirrhosis and even liver cancer. Fatty liver disease is largely considered to be a direct consequence of obesity. It is not only people in Europe and the USA who have put on enormous amounts of weight in recent decades; obesity is also becoming increasingly widespread in emerging countries such as India and China. As a result, the number of cases of liver failure and liver cancer is rising sharply in the countries affected.

“The vicious circle of an unhealthy diet, obesity, liver inflammation and liver cancer is associated with major restrictions and suffering for those affected and also represents a considerable burden on healthcare systems,” says Mathias Heikenwälder, DKFZ and University of Tübingen. “We have therefore investigated whether simple dietary changes can specifically interrupt this fatal process.”

Intermittent fasting has already been shown in several studies to be an effective means of reducing weight and alleviating certain metabolic disorders. Heikenwälder’s team has now tested in mice whether this approach can also protect the liver from fatty degeneration and chronic inflammation.

Resistance to liver inflammation is independent of calorie intake

The animals were fed with a high-sugar and high-fat diet correspondind to the typical Western diet. One group of mice had constant access to the food. As expected, these animals gained weight and body fat and developed chronic liver inflammation.

The mice in the other group were given nothing to eat on two days a week (5:2 intermittent fasting, or 5:2 IF for short), but were allowed to eat as much as they wished on the other days. Despite the high-calorie diet, these animals did not put on weight, showed fewer signs of liver disease and had lower levels of biomarkers that indicate liver damage. In short, they were resistant to the development of MASH.

Interestingly, resistance to the development of a fatty liver was independent of the total calorie intake, as the animals immediately made up for the lost rations after the end of the fasting periods.

When experimenting with different variants of intermittent fasting, it was found that several parameters determine protection against liver inflammation: The number and duration of fasting cycles play a role, as does the start of the fasting phase. A 5:2 dietary pattern works better than 6:1; 24-hour fasting phases better than 12-hour ones. A particularly unhealthy diet requires more frequent dieting cycles.

Heikenwälder’s team now wanted to find out the molecular background of the response to fasting. To this end, the researchers compared protein composition, metabolic pathways and gene activity in the liver of fasting and non-fasting mice. Two main players responsible for the protective fasting response emerged: the transcription factor PPARα and the enzyme PCK1. The two molecular players work together to increase the breakdown of fatty acids and gluconeogenesis and inhibit the build-up of fats.

“The fasting cycles lead to profound metabolic changes, which together act as beneficial detoxification mechanisms and help to combat MASH,” says Heikenwälder, summarizing the molecular details.

The fact that these correlations are not just a mouse phenomenon was shown when tissue samples from MASH patients were examined: Here, too, the researchers found the same molecular pattern with reduced PPAR α and PCK1. Are PPAR α and PCK1 actually responsible for the beneficial effects of fasting? When both proteins were genetically switched off simultaneously in the liver cells of the mice, intermittent fasting was unable to prevent either chronic inflammation or fibrosis.

The drug pemafibrate mimics the effects of PPARα in the cell. Can the substance also mimic the protective effect of fasting? The researchers investigated this question in mice. Pemafibrate induced some of the favorable metabolic changes that were observed with 5:2 fasting. However, it was only able to partially mimic the protective effects of fasting. “This is hardly surprising, as we can only influence one of the two key players with pemafibrate. Unfortunately, a drug that mimics the effects of PCK1 is not yet available,” explains Mathias Heikenwälder.

Intermittent fasting as liver therapy

While Heikenwälder and his team initially focused on the effects of intermittent fasting on the prevention of MASH, they then investigated whether the 5:2 diet could also alleviate existing chronic liver inflammation.

To this end, the team examined mice that had developed MASH after months of being fed a high-sugar, high-fat diet. After a further four months of 5:2 intermittent fasting (on the same diet), these animals were compared with the non-fasting control group. The fasting mice had better blood values, less fatty liver and liver inflammation and above all: they developed less liver cancer and had fewer cancer foci in the liver.

“This shows us that 5:2 intermittent fasting has great potential – both in the prevention of MASH and liver cancer, as well as in the treatment of established chronic liver inflammation,” summarizes principal investigator Heikenwälder. “The promising results justify studies in patients to find out whether intermittent fasting protects against chronic liver inflammation as well as in the mouse model.”

The 5:2 fasting regimen is popular. It is considered comparatively easy to integrate into everyday life, as the fasting days can be tailored to personal needs and no specific foods are prohibited. “Nevertheless, there will always be people who can’t stick to a strict diet in the long term,” says Heikenwälder. “That’s why we want to continue to investigate which combinations of drugs we can use to fully mimic the protective effects of fasting.”

Why was it necessary to study mice for this experiments?

A high-calorie, unbalanced diet and a sedentary lifestyle are contributing to the sharp rise in the proportion of obese people in many parts of the world. Obesity also increases the risk of a whole range of secondary diseases for those affected, including cardiovascular diseases, metabolic diseases, cancer and joint problems. Understanding these correlations and, ideally, intervening in a targeted manner is an extremely important research goal.

Several organs and organ systems are jointly involved in the development of obesity-related health consequences. The liver, pancreas, brain, lymphatic organs and fatty tissue work together here, which cannot be simulated in the culture dish. The intestine can also play a role in the development of MASH. The spontaneous development of liver cancer from a fatty liver can therefore only be recapitulated and investigated if all these factors interact.

Also crucial is the influence of immune cells that migrate from the periphery of the body into the fatty liver, are activated there and migrate back into the body, where they interact with the fatty tissue. This can only be investigated in an intact organism. Experiments with mice are also necessary to understand which length of fasting periods achieves the most favorable health results in the context of the circadian (day/night) rhythm.

Reference:

Suchira Gallage, Adnan Ali, Jose Efren Barragan Avila, Nogayhan Seymen, Pierluigi Ramadori, Vera Joerke, Laimdota Zizmare, David Aicher, Indresh K. Gopalsamy, Winnie Fong, Jan Kosla, Enrico Focaccia, Xin Li, Suhail Yousuf, Tjeerd Sijmonsma, Mohammad Rahbari, Katharina S. Kommoss, Adrian Billeter, Sandra Prokosch, Ulrike Rothermel, Florian Mueller, Jenny Hetzer, Danijela Heide, Benjamin Schinkel, Tim Machauer, Bernd Pichler, Nisar P. Malek, Thomas Longerich, Susanne Roth, Adam J. Rose, Johannes Schwenck, Christoph Trautwein, Mohammad M. Karimi, Mathias Heikenwalder, A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1, Cell Metabolism, https://doi.org/10.1016/j.cmet.2024.04.015.

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Cannabis, nicotine use during pregnancy increases rate of infant death fourfold, reveals JAMA study

Oregon Health & Science University researchers in a new study report that combined cannabis and nicotine use during pregnancy is associated with significantly higher risk of poor health outcomes for newborns compared with use of either substance alone.

The study, published today in JAMA Network Open, found infants born to mothers who used both substances throughout pregnancy were at greater risk of being small for gestational size, undergoing preterm delivery, or even death.

With approximately half of individuals who use cannabis in pregnancy also using tobacco or nicotine products, the findings suggest the need for more effective clinical counseling early on, during the preconception and prenatal periods, said the study’s corresponding author, Jamie Lo, M.D., M.C.R., associate professor of obstetrics and gynecology (maternal-fetal medicine) in the OHSU School of Medicine and Division of Reproductive and Developmental Sciences at OHSU’s Oregon National Primate Research Center.

“With the growing legalization of cannabis around the country, there is often a perception that cannabis is safe in pregnancy,” Lo said. “Because we know that many people who use cannabis often use tobacco or nicotine products, we wanted to better understand the potential health implications on both the pregnant individual and the infant.

“There is still a great deal of stigma around the use of substances during pregnancy,” she continued. “With limited research to support official clinical recommendations, it can be a difficult topic for both patients and providers to navigate. Our hope is that this research supports more open and productive conversations that ultimately result in a healthier pregnancy.”

Researchers evaluated hospital discharge data and vital statistics from more than 3 million pregnant patients with documented cannabis and nicotine use. Compared with people who didn’t use any substances, those using cannabis or nicotine alone had increased rates of infant and newborn death, small gestational size and preterm delivery-but the risk was even higher when both cannabis and nicotine were used together.

Most notable was the rate of infant death, which was four times higher in users of both cannabis and nicotine compared with non-users. The rate was nearly two times higher compared with users of just cannabis or nicotine alone.

The research team says these findings can help guide health care professionals with preconception and prenatal counseling, especially regarding the benefits of quitting at least one of the two substances. They also support expanded efforts to educate pregnant people about the risks of cannabis and nicotine.

“We hope that pregnant individuals can abstain from using both cannabis and nicotine products. However, we acknowledge the complexities of individual circumstances may make this goal challenging, and for some patients is simply not realistic,” said Adam Crosland, M.D., M.P.H., assistant professor of obstetrics and gynecology in the OHSU School of Medicine and lead author of the study. “We always strive to meet people where they are and support patients with evidence-based recommendations and treatment options that are both patient-centered and promote the healthiest outcomes possible.

“Our findings suggest that avoiding use of just one of these substances can decrease the pregnancy risks we see when both substances are used together, which is a critical piece of information providers can highlight when counseling patients.”

The multidisciplinary research team also included Eliot Spindel, M.D., Ph.D., and Cindy McEvoy, M.D., M.C.R., who are investigating how to mitigate the negative respiratory outcomes among children born to parents who smoke during pregnancy. McEvoy’s team found that vitamin C supplementation to pregnant women unable to quit smoking cigarettes significantly improves airway function and respiratory health in their offspring; moreover, these improved outcomes persist through age 5 and these children are in continued follow-up through adolescence.

Looking ahead, researchers will continue to investigate the effects of combined cannabis and nicotine use-including the influence of potency, frequency and timing-in order to better educate pregnant patients about the harms of use. Additionally, the team will continue to explore the viability of prenatal interventions, such a vitamin C supplementation, and other treatment options for individuals who are unable to quit smoking during their pregnancy.

Reference:

Crosland BA, Garg B, Bandoli GE, et al. Risk of Adverse Neonatal Outcomes After Combined Prenatal Cannabis and Nicotine Exposure. JAMA Netw Open. 2024;7(5):e2410151. doi:10.1001/jamanetworkopen.2024.10151.

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Pediatric hypertension associated with long-term cardiovascular events: JAMA

A recent study from Ontario, Canada illuminated the long-term risks associated with childhood hypertension. This comprehensive study underlines the pressing need for increased awareness and effective management of hypertension in children. The major findings of this study were published in the recent issue of Journal of American Medical Association.

Hypertension was once considered primarily an affliction of adulthood is increasingly affecting children with its estimates suggesting to 6% effect on all children and which is still on the rise. Despite this trend, the evidence that links childhood hypertension to adverse cardiovascular outcomes was lacking, which leads to underdiagnosis and undertreatment.

This population-based, retrospective, matched cohort analysis meticulously examined the data from 1996 to 2022 and encompassed all children who were aged 3 to 18 years in Ontario. The research identified children with incident hypertension using validated case definitions derived from diagnostic and physician billing claims. Following this, they matched them with controls without hypertension based on various parameters including age, sex, birth weight, maternal gestational hypertension and prior comorbidities.

Over a median follow-up period of 13.6 years, the children who were diagnosed with hypertension expressed a significantly higher risk of major adverse cardiac events (MACE) when compared to their non-hypertensive counterparts. These events included cardiovascular death, stroke, hospitalization for myocardial infarction or unstable angina, coronary intervention and congestive heart failure.

The incidence of MACE was significantly higher among the children with hypertension with a rate of 4.6 per 1000 person-years when compared to 2.2 per 1000 person-years in controls. This translates to a more than twofold increased risk of MACE among the children with hypertension which emphasizes the profound impact of hypertension on cardiovascular health even from a young age.

While prior comorbidities such as malignancy, congenital heart disease and diabetes were uncommon in both cohorts, hypertension remained a significant independent risk factor for adverse cardiovascular outcomes. The implications of these findings underline the critical importance of early detection, regular monitoring and effective management of hypertension in children to reduce the long-term risks of cardiovascular disease in adulthood. Overall, clinicians can potentially avert a substantial burden of cardiovascular morbidity and mortality in the future by addressing hypertension in childhood. 

Source:

Robinson, C. H., Hussain, J., Jeyakumar, N., Smith, G., Birken, C. S., Dart, A., Dionne, J., Garg, A., Kandasamy, S., Karam, S., Marjerrison, S., South, A. M., Thabane, L., Wahi, G., Zappitelli, M., & Chanchlani, R. (2024). Long-Term Cardiovascular Outcomes in Children and Adolescents With Hypertension. In JAMA Pediatrics. American Medical Association (AMA). https://doi.org/10.1001/jamapediatrics.2024.1543

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30-year US study links ultra-processed food to higher risk of early death

Higher consumption of most ultra-processed foods is linked to a slightly higher risk of death, with ready-to-eat meat, poultry, and seafood based products, sugary drinks, dairy based desserts, and highly processed breakfast foods showing the strongest associations, finds a 30-year US study in The BMJ today.

The researchers say not all ultra-processed food products should be universally restricted, but that their findings “provide support for limiting consumption of certain types of ultra-processed food for long term health.”

Ultra-processed foods include packaged baked goods and snacks, fizzy drinks, sugary cereals, and ready-to-eat or heat products. They often contain colours, emulsifiers, flavours, and other additives and are typically high in energy, added sugar, saturated fat, and salt, but lack vitamins and fibre.

Mounting evidence links ultra-processed foods to higher risks of obesity, heart disease, diabetes and bowel cancer, but few long term studies have examined links to all cause and cause specific deaths, especially due to cancer.

To address this knowledge gap, researchers tracked the long-term health of 74,563 female registered nurses from 11 US states in the Nurses’ Health Study (1984-2018) and 39,501 male health professionals from all 50 US states in the Health Professionals Follow-up Study (1986-2018) with no history of cancer, cardiovascular diseases, or diabetes at study enrolment.

Every two years participants provided information on their health and lifestyle habits, and every four years they completed a detailed food questionnaire. Overall dietary quality was also assessed using the Alternative Healthy Eating Index-2010 (AHEI) score.

During an average 34-year follow-up period, the researchers identified 48,193 deaths, including 13,557 deaths due to cancer, 11,416 deaths due to cardiovascular diseases, 3926 deaths due to respiratory diseases, and 6343 deaths due to neurodegenerative diseases.

Compared with participants in the lowest quarter of ultra-processed food intake (average 3 servings per day), those in the highest quarter (average 7 servings per day) had a 4% higher risk of total deaths and a 9% higher risk of other deaths, including an 8% higher risk of neurodegenerative deaths.

No associations were found for deaths due to cardiovascular diseases, cancer, or respiratory diseases.

In absolute numbers, the rate of death from any cause among participants in the lowest and highest quarter of ultra-processed food intake was 1472 and 1536 per 100,000 person years, respectively.

The association between ultra-processed food intake and death varied across specific food groups, with meat, poultry, and seafood based ready-to-eat products showing the strongest and most consistent associations, followed by sugar sweetened and artificially sweetened beverages, dairy based desserts, and ultra-processed breakfast food.

And the association was less pronounced after overall dietary quality was taken into account, suggesting that dietary quality has a stronger influence on long term health than ultra-processed food consumption, note the authors.

This is an observational study, so no firm conclusions can be drawn about cause and effect, and the authors point out that the ultra-processed food classification system does not capture the full complexity of food processing, leading to potential misclassification. In addition, participants were health professionals and predominantly white, limiting the generalizability of the findings.

However, this was a large study with long follow-up, using detailed, validated, and repeated measurements, and results were similar after further analyses, providing greater confidence in the conclusions.

The researchers stress that not all ultra-processed food products should be universally restricted and say oversimplification when formulating dietary recommendations should be avoided.

But they conclude: “The findings provide support for limiting consumption of certain types of ultra-processed food for long term health,” adding that “future studies are warranted to improve the classification of ultra-processed foods and confirm our findings in other populations.”

In a linked editorial, researchers in New Zealand point out that recommendations to avoid ultra-processed food may also give the impression that foods that are not ultra-processed, such as red meat, can be frequently consumed.

They argue that debate about the ultra-processed concept must not delay food policies that improve health, such as restrictions on marketing unhealthy foods to children, warning labels on nutritionally poor food products, and taxes on sugary drinks.

“Our focus should be on advocating for greater global adoption of these and more ambitious interventions and increasing safeguards to prevent policies from being influenced by multinational food companies with vested interests that do not align with public health or environmental goals,” they conclude.

Reference:

https://www.bmj.com/content/385/bmj-2023-078476

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Lung abnormality progression linked to acute respiratory disease in smokers, claims study

Smokers who have small abnormalities on their CT scans that grow over time have a greater likelihood of experiencing acute respiratory disease events, according to a new study published in Radiology, a journal of the Radiological Society of North America (RSNA).

Quantitative interstitial abnormalities (QIA) are subtle abnormalities on chest CTs that do not meet the diagnostic criteria for advanced pulmonary diseases but are nonetheless associated with decreased lung function and capacity, increased respiratory symptoms and death.

“QIA includes features like reticulation and ground-glass opacities as well as subtle density changes with important clinical implications,” said Bina Choi, M.D., associate physician in the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital and postdoctoral fellow at the Applied Chest Imaging Laboratory, Harvard Medical School in Boston. “In some patients, QIA may be a precursor to advanced diseases such as pulmonary fibrosis or emphysema.”

Acute respiratory disease events are episodes of increased cough, phlegm or shortness of breath that last at least two days and require treatment with steroids or antibiotics. Severe acute respiratory disease episodes require an emergency room visit or hospitalization.

“We wanted to determine whether progression in QIA on chest CT is associated with acute respiratory disease events in individuals with a history of smoking,” Dr. Choi said. “While many acute respiratory disease events are likely related to airway disease and COPD, some may instead be associated with QIA especially in people without obstruction or emphysema.”

Dr. Choi’s team performed a secondary analysis of the CT scans of 3,972 participants (mean age 60.7; 2,120 women) in the COPDGene® Study, one of the largest studies ever to investigate the underlying genetic factors of COPD. The study included individuals with a 10-pack-year or greater smoking history recruited from multiple centers between November 2007 and July 2017.

QIA was measured with machine learning-based tools as a percentage of lung volume on a CT scan. QIA progression was assessed using the participants’ QIA measurements at baseline and five-year follow-up CT exams.

Statistical analyses revealed that participants in the highest quartile of QIA progression had more frequent acute respiratory disease and severe acute respiratory disease events than those in the lowest quartile.

“We found that progression in QIA is independently associated with these acute respiratory disease events both intercurrent and subsequent to progression,” she said.

Dr. Choi said the results suggest that QIA progression may represent changes in lung tissue processes that have both short- and long-term impacts on patient symptoms and the worsening of those symptoms.

“Severe acute respiratory disease events may be a sign of disease activity and a source of morbidity at the earliest stages of lung tissue injury,” she said. “Some people with QIA progression may merit more aggressive monitoring and earlier intervention.”

Reference:

Bina Choi , Alejandro A. Díaz, Ruben San José Estépar, Nicholas Enzer, Victor Castro, MeiLan K. Han, George R. Washko, Association of Acute Respiratory Disease Events with Quantitative Interstitial Abnormality Progression at CT in Individuals with a History of Smoking, Radiology, https://doi.org/10.1148/radiol.231801.

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Weight-loss surgery before kidney transplantation improves health and eligibility of patients with obesity and renal failure, finds study

Laparoscopic sleeve gastrectomy promotes relatively rapid weight loss, reduces obesity-related health issues and improves eligibility for kidney transplantation for patients with advanced chronic kidney disease and obesity, according to new research from Mayo Clinic.

Patients with advanced chronic kidney failure and severe obesity often are not considered for kidney transplantation, but according to a study published in Mayo Clinic Proceedings, sleeve gastrectomy can improve high-risk patients meeting the criteria for transplantation. The findings also show that the surgical weight-loss procedure reduced cardiovascular risks, including diabetes and hypertension.

“In earlier research, we found that conservative weight-loss approaches do not adequately result in significant weight loss in patients with advanced chronic kidney disease,” says Aleksandra Kukla, M.D., a Mayo Clinic transplant nephrologist and the study’s first author. “These new findings support the value of surgical gastrectomy for patients with advanced chronic kidney failure, stage 4-5D, to improve general health and access to kidney transplantation.”

The retrospective study involved 104 patients with advanced chronic kidney failure and obesity who were treated at Mayo Clinic between 2020 and 2023. Fifty-four underwent laparoscopic sleeve gastrectomy, the most frequently performed surgical weight-loss procedure in patients seeking kidney transplant, and 50 patients opted for a nonsurgical weight-loss approach.

Undergoing sleeve gastrectomy reduced the time for patients to be added to waiting lists for kidney transplantation. It also improved the likelihood of receiving a transplant, with 37% of those who underwent sleeve gastrectomy receiving a transplant within 18 months, versus 10% in the nonsurgical cohort.

The risk of postsurgical complications was low, and the rate of hospitalizations and infections for patients who underwent sleeve gastrectomy was similar to the nonsurgical cohort.

Effective therapy for obesity among patients with advanced chronic kidney disease is understudied, in part because high body mass index (BMI) is often considered beneficial in patients receiving kidney dialysis. “Treatment of obesity in this population has been limited to nonsurgical options in the past,” says Tayyab Diwan, M.D., a Mayo Clinic transplant surgeon and co-author of the study.

More research is needed on the optimal timing of the surgery for kidney transplant candidates, Dr. Diwan says.

Reference:

Aleksandra Kukla, Sukhdeep S. Sahi, Pavel Navratil, Roberto P. Benzo, Byron H. Smith, Dustin Duffy, Walter D. Park, Meera Shah, Pankaj Shah, Matthew M. Clark, David C. Fipps, Aleksandar Denic, Carrie A. Schinstock, Patrick G. Dean, Mark D. Stegall, Yogish C. Kudva, Tayyab S. Diwan, Weight Loss Surgery Increases Kidney Transplant Rates in Patients With Renal Failure and Obesity, Mayo Clinic Proceedings, https://doi.org/10.1016/j.mayocp.2024.01.017.

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Strength training improves knee health, lowers risk of knee osteoarthritis: Study

USA: It has been assumed for a long time that strength training has adverse effects. Now, a recent study published in Arthritis & Rheumatology has counteracted this assumption stating that strength training is beneficial for future knee health and lowers the risk of knee osteoarthritis (OA).

“Participants with a history of strength training had a 17% to 23% lower risk of developing frequent knee pain, radiographic OA, and symptomatic OA,” reported Grace H. Lo, Michael E. DeBakey Medical Center, Houston, Texas, and colleagues.

The research team aimed to evaluate the relationship of a history of strength training with symptomatic and structural outcomes of knee OA. They conducted a retrospective, cross-sectional study within the Osteoarthritis Initiative (OAI), a multicenter prospective longitudinal observational study.

For this purpose, the researchers reviewed data on strength training and knee pain from 2607 adults. The Historical Physical Activity Survey Instrument was used to assess the impact of strength training during four periods (ages 12–18 years, 19–34 years, 3549 years, and 50 years and older). The participants were enrollees of the Osteoarthritis Initiative; 44% were male, the average age was 64.3 years, and the mean body mass index (BMI) was 28.5 kg/m2.

Strength training was defined as those exposed and those not exposed, and divided into low, medium, and high tertiles for those exposed; a total of 818 individuals were exposed to strength training, and 1789 were not exposed to strength training.

The study’s primary outcomes were frequent knee pain, radiographic OA (ROA), and symptomatic radiographic OA (SOA).

The study led to the following findings:

  • Strength training at any point in life was associated with a lower incidence of frequent knee pain, ROA, and SOA, compared with no strength training (odds ratios, 0.82, 0.83, and 0.77, respectively).
  • When separated by tertiles, only the high-exposure group had significantly reduced odds of frequent knee pain, ROA, and SOA, with odds ratios of 0.74, 0.70, and 0.69, respectively; a dose-response relationship appeared for all three conditions, with the lowest odds ratios in the highest strength training exposure groups.
  • Findings were similar for different age ranges, but the association between strength training and less frequent knee pain, less ROA, and less SOA was strongest in the older age groups.

“Our findings support the idea that the medical community should proactively encourage more people to participate in strength training to help lower their risk of osteoarthritis and other chronic conditions,” the researchers write.

This study, however, was limited by its potential selection bias, observational nature, and the inability to rule out reverse causation or confounding.

Reference:

Lo, G. H., Richard, M. J., McAlindon, T. E., Kriska, A. M., Price, L. L., Rockette-Wagner, B., Eaton, C. B., Hochberg, M. C., Kwoh, C. K., Nevitt, M. C., & Driban, J. B. Strength Training Is Associated With Less Knee Osteoarthritis: Data From the Osteoarthritis Initiative. Arthritis & Rheumatology. https://doi.org/10.1002/art.42732

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Hospital acquired gram positive infections linked to increased mortality in cirrhosis patients admitted to ICU: Study

A recent study published in the recent issue of Annals of Intensive Care shed light on a previously overlooked area of hospital-acquired bloodstream infections in the ICU, especially for patients with cirrhosis.

This study was conducted across 101 centers and analyzed data from the Eurobact-2 international cohort study by encompassing a total of 1059 cases of hospital-acquired bloodstream infections. This study underlines the increased vulnerability of cirrhotic patients to infections contracted within hospital walls. Cirrhotic patients who accounted for 160 of the cases showed a distinctive epidemiological profile when compared to their non-cirrhotic counterparts.

The variance in infection sources was a crucial finding of this study. While non-cirrhotic patients predominantly suffered from pulmonary infections, cirrhotic patients were more susceptible to abdominal sources that hinted at underlying physiological factors that could possibly influence the infection localization.

Cirrhotic patients expressed a predilection for Gram-positive infections, notably Enterococcus faecium. The prevalence of this pathogen was significantly higher among the cirrhotic patients that underlined a potential association between cirrhosis and increased susceptibility to specific pathogens. The association between cirrhosis and Enterococcus faecium infections remained profound even after adjusting for confounding factors which highlighted the distinct microbial landscape within cirrhotic patients.

The study uncovered a concerning trend in mortality rates. Cirrhotic patients afflicted with hospital-acquired bloodstream infections faced a 30% higher risk of mortality when compared to their non-cirrhotic counterparts. This underlines the urgent need for tailored interventions and elevated surveillance protocols to reduce the impact of infections in this vulnerable population.

The findings emphasized the significance of this study in guiding clinical management strategies for critically ill cirrhotic patients. Understanding the unique epidemiological nuances of the infections in cirrhotic patients is critical in improving the patient outcomes and reducing mortality rates

The benefits of this study extend beyond the ICU which prompts a reevaluation of infection prevention and control measures in hospital settings. With increase in the prevalence of cirrhosis, proactive measures that target this high-risk population could yield substantial benefits in reducing the burden of hospital-acquired infections.

Source:

Wozniak, H., Tabah, A., Barbier, F., Ruckly, S., Loiodice, A., Akova, M., Leone, M., Conway Morris, A., Bassetti, M., Arvaniti, K., Ferrer, R., de Bus, L., Paiva, J. A., Bracht, H., Mikstacki, A., Alsisi, A., Valeanu, L., Prazak, J., … Timsit, J.-F. (2024). Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study. In Annals of Intensive Care (Vol. 14, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1186/s13613-024-01299-x

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Axillary lymph node dissection effective for breast cancer with sentinel-node macrometastases: Study

A recent clinical trial determined that omitting the routine procedure of completion axillary-lymph-node dissection (ALND) does not compromise the survival rates of patients with certain types of breast cancer by potentially setting the stage for less invasive treatment options. The findings were published in The New England Journal of Medicine.

The study included 2,766 participants across five countries from January 2015 to December 2021 and looked at patients with clinically node-negative primary T1 to T3 breast cancers where the patients had either one or two sentinel-node macrometastases. These patients would undergo ALND, where additional lymph nodes are surgically removed after the sentinel lymph node is found to contain cancer.

The participants were randomly assigned to either proceed with the standard ALND or to undergo only a sentinel-node biopsy (SNB) where only the first few lymph nodes into which a tumor drains are removed and examined. The primary goal was to compare overall survival rates while the secondary outcomes focused on the recurrence-free survival

The omission of ALND did not show inferior results when compared to the traditional approach. In fact, the 5-year recurrence-free survival rates were impressive with 89.7% in the SNB-only group and 88.7% in the dissection group. The hazard ratio was 0.89 (95% CI, 0.66 to 1.19) which was significantly under the preset threshold.

Also, the vast majority of patients in both groups received radiation therapy that included nodal target volumes, with 89.9% in the SNB-only group and 88.4% in the group undergoing dissection. This consistency in post-operative treatment underscores the rigorous standards maintained across the study.

These findings are pivotal as they suggest that for certain patients with node-negative breast cancer, the less invasive procedure of sentinel-node biopsy alone could be just as effective as more extensive surgery to prevent cancer recurrence. This could directly translate to fewer surgical complications, quicker recovery times and potentially lower healthcare costs. Overall, the significant changes in the surgical management of breast cancer offers many patients a less invasive option without compromising their long-term health outcomes.

Reference:

de Boniface, J., Filtenborg Tvedskov, T., Rydén, L., Szulkin, R., Reimer, T., Kühn, T., Kontos, M., Gentilini, O. D., Olofsson Bagge, R., Sund, M., Lundstedt, D., Appelgren, M., Ahlgren, J., Norenstedt, S., Celebioglu, F., Sackey, H., Scheel Andersen, I., Hoyer, U., Nyman, P. F., … Christiansen, P. (2024). Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases. In New England Journal of Medicine (Vol. 390, Issue 13, pp. 1163–1175). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2313487

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Vitamin D levels among neonates born after IVF higher compared to neonates from general population: Study

Vitamin D levels among neonates born after IVF are higher compared with neonates from the general population suggests a study published in the Acta Obstetricia et Gynecologica Scandinavica.

Sufficient levels of vitamin D have been associated with higher chances for both clinical pregnancy and live birth among women undergoing assisted reproductive techniques, whereas low levels of maternal vitamin D have been associated with preeclampsia and late miscarriage. In Denmark, subgroups at risk for low vitamin D levels, including neonates and toddlers, are recommended to use supplementation. The aim was to study the level of vitamin D3 among neonates born after in vitro fertilization compared with neonates from the general population. In this cohort study a random sample of 1326 neonates representing the general population and 1200 neonates conceived by in vitro fertilization born in Denmark from 1995 to 2002 were identified from registries covering the whole Danish population. Information on use of assisted reproduction was collected from the Danish In Vitro Fertilization register, ICD-10 code: DZ358F. 25-Hydroxyvitamin D was measured from dried blood spots routinely collected by heel prick 48-72 h after birth and corrected according to the hematocrit fraction for capillary blood of neonates. Linear regression analysis was performed, both crude and adjusted, for predefined putative confounders, identified through directed acyclic graphs. Results: Vitamin D3 analysis could be performed from a total of 1105 neonates from the general population and 1072 neonates conceived by in vitro fertilization that were subsequently included in the study. The median vitamin D3 was 24.0 nmol/L (interquartile range [IQR] 14.1-39.3) and 33.0 nmol/L (IQR 21.3-48.8) among neonates from the general population and neonates conceived by in vitro fertilization, respectively. The adjusted mean difference between neonates from the general population and those conceived by in vitro fertilization was 6.1 nmol/L (95% confidence interval 4.1-8.1). In this study, children born after in vitro fertilization have a higher vitamin D3 than a random sample of neonates in Denmark.

Reference:

Walker KC, Pristed SG, Thorsteinsdottir F, Specht IO, Cohen A, Heitmann BL, Kesmodel US. Vitamin D3 among neonates born after in vitro fertilization compared with neonates from the general population. Acta Obstet Gynecol Scand. 2024 Apr 18. doi: 10.1111/aogs.14819. Epub ahead of print. PMID: 38637997.

Keywords:

Vitamin D levels, neonates, born, IVF higher, neonates, general, population, Acta Obstetricia et Gynecologica Scandinavica, Walker KC, Pristed SG, Thorsteinsdottir F, Specht IO, Cohen A, Heitmann BL, Kesmodel US, in vitro fertilization; infertility; neonate; vitamin D.

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