Archive for category: News

C-INFIX safe with low complication rates among patients with pelvic unstable injuries suggests a new study published in the BMC Surgery.

In a recent study, Filipe Dal-Pizzol and colleagues explored the potential of minocycline in preventing delirium among critically ill patients. Delirium, a severe form of acute encephalopathy, poses significant risks to patients in Intensive Care Units (ICUs). The findings were published in CHEST Journal.

This randomized, placebo-controlled, double-blind trial conducted across four ICUs and aimed to determine if minocycline could be a potential drug in managing this occurrence of delirium. This research included 159 patients and revealed a significant decrease in delirium incidence among those treated with minocycline. Compared to the placebo group, the minocycline recipients showed a lower occurrence of delirium (20% vs. 35%), marking a small but statistically significant improvement.

Beyond delirium incidence, the study explored various secondary outcomes such as delirium/coma free days, length of mechanical ventilation, and mortality rates. Intriguingly, minocycline treatment unexpectedly correlated with a significant decrease in hospital mortality (23% vs. 39%). This unanticipated finding adds a layer of complexity to the potential benefits of minocycline in critical care.

Exploratory outcomes involved monitoring inflammatory and brain-related biomarkers. While the study found a significant decrease in plasma levels of C-reactive protein after minocycline treatment, the broader implications of these changes are yet to be fully understood.

This study opens a promising avenue for future research into the use of minocycline as a neuroprotective agent in critical care settings. The potential to mitigate delirium, coupled with unexpected reductions in mortality, underscores the urgency of more extensive studies to validate these findings and explore the broader applications of minocycline in critical care protocols. Larger and well-structured studies are crucial to confirm the potential benefits of minocycline as a preventive measure against delirium in critically ill patients.

Reference:

Dal-Pizzol, F., Coelho, A., Simon, C. S., Michels, M., Corneo, E., Jeremias, A., Damásio, D., & Ritter, C. (2023). Prophylactic minocycline for delirium in critically ill patients: a randomized controlled trial. In CHEST. Elsevier BV. https://doi.org/10.1016/j.chest.2023.11.041

A study published in the Journal of Oral and Facial Pain and Headache reveals that individuals with painful myogenous temporomandibular disorders (TMDs) often experience a concurrent presence of fibromyalgia and chronic widespread pain (CWP).

Fibromyalgia, recognized as a subtype within chronic widespread pain (CWP), is defined by pervasive musculoskeletal pain. The coexistence of temporomandibular disorders (TMD) and fibromyalgia is commonly acknowledged as a duo of chronic overlapping pain conditions (COPCs). Additionally, conditions such as migraine, chronic tension-type headache, chronic lower back pain, chronic fatigue syndrome, and irritable bowel syndrome (IBS) are also classified as COPCs. 

Despite numerous studies exploring the coexistence of fibromyalgia and temporomandibular disorders (TMDs), the connection between these two conditions remains unclear. Clarifying the epidemiological aspect of this association is crucial for the accurate diagnosis and management of patients experiencing these conditions. Hence, this study was conducted with the recognition of this need for understanding.

To ascertain the prevalence of chronic widespread pain and fibromyalgia in individuals with temporomandibular disorders and vice versa, a thorough search was systematically carried out across electronic databases. The quality of the studies was evaluated using the Newcastle-Ottawa Scale, and meta-analyses employing specific diagnostic criteria were employed to assess pooled prevalence estimates.

The assessment incorporated 19 studies of moderate to high quality, comprising 9 studies examining the prevalence of chronic widespread pain or fibromyalgia in individuals with temporomandibular disorders, and 10 studies evaluating the prevalence of TMDs in those with CWP or fibromyalgia. Among these studies, 10 were case-control, 6 were cross-sectional, and 3 were cohort studies. Heterogeneity across the pooled studies was noted, attributed to variations in criteria guidelines, protocols, subjective patient and clinician assessments, and differences in application over time.

The key findings of this study were:

As indicated by the meta-analyses, three-quarters of individuals with fibromyalgia concurrently had temporomandibular disorders (76.8% [69.5% – 83.3%]), and around one-third of those with temporomandibular disorders had comorbid fibromyalgia (32.7%, 4.5% – 71.0%).

In comparison to disc displacement disorders, myogenous temporomandibular disorders were more prevalent in this patient group (63.1% [47.7% – 77.3%] vs. 24.2% [19.4% – 39.5%], respectively). Additionally, comorbid inflammatory degenerative temporomandibular disorders were observed in 41.8% (21.9% – 63.2%) of individuals with fibromyalgia.

The highest percentages of patients with temporomandibular disorders exhibiting symptoms of fibromyalgia were noted in a study of individuals with painful disorders of the masticatory muscles lasting ≥6 months (63.2%) and in a study where patients were referred to a physiatrist for the evaluation of potential fibromyalgia (52.4%).

These results imply that clinicians should take into account the intersection of temporomandibular disorders with chronic widespread pain and fibromyalgia when providing care to affected individuals. Additionally, in suitable cases, adopting multidisciplinary approaches to treatment may be beneficial.

Source:

Dibello, V., Lozupone, M., Sardone, R., Ballini, A., Lafornara, D., Dibello, A., Vertucci, V., Santarcangelo, F., Maiorano, G., Stallone, R., Petruzzi, M., Daniele, A., Solfrizzi, V., & Panza, F. (2023). Temporomandibular Disorders as Contributors to Primary Headaches: A Systematic Review. In Journal of Oral & Facial Pain and Headache (Vol. 37, Issue 2, pp. 91–100). Quintessence Publishing. https://doi.org/10.11607/ofph.3345

USA: A recent preclinical study from researchers at Weill Cornell Medicine points to the possibility of using cholesterol-lowering drugs to prevent or treat hard-to-detect colorectal pre-cancerous lesions known as serrated polyps, and the aggressive tumours that develop from them. 

According to the study, published in Nature Communications, such tumors depend heavily on the ramped-up production of cholesterol. 

In the study, the researchers analyzed mice that develop serrated polyps and tumours, detailing the chain of molecular events in these tissues that leads to increased cholesterol production.

They confirmed their findings in analyses of human serrated polyps and tumours, and showed in mouse models that replicate the human cancer that blocking cholesterol production prevented the progression of these types of intestinal tumors.

“Serrated-type polyps and tumors currently are not treated differently from other colorectal neoplasias, but as our work shows, they have this specific metabolic vulnerability that can be targeted,” said study co-senior author Dr. Jorge Moscat, a Homer T. Hirst III Professor of Oncology in Pathology, Vice-Chair for Cell and Cancer Pathobiology in the Department of Pathology and Laboratory Medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

The other co-senior author is Dr. Maria Diaz-Meco, also a Homer T. Hirst III Professor of Oncology in Pathology and a member of the Meyer Cancer Center at Weill Cornell Medicine. The study’s first author is Dr. Yu Muta, a postdoctoral associate in the Moscat/Diaz-Meco laboratories.

Cholesterol is generally considered a pro-growth molecule, being a building block for cell membranes and having other growth-supporting functions. Prior studies have linked high blood cholesterol levels to various cancers, including colorectal cancers. However, it hasn’t been clear that lowering cholesterol, for example with common statin drugs, can prevent colorectal cancers.

“Trials of statins to prevent colorectal cancer have had conflicting results,” Dr. Diaz-Meco said. “Our findings suggest that this is because targeting cholesterol has a preventive but selective effect only against polyps and tumors of this serrated type.”

Serrated polyps are so-called because of their sawtooth appearance under a microscope. They are flatter than ordinary colorectal polyps and can often be missed during colonoscopies. Yet the tumors into which they develop, which account for roughly 15 to 30 percent of colorectal cancers, contain many “metaplastic” cells that are particularly invasive and resistant to treatments.

Several years ago, the Moscat/Diaz-Meco team linked serrated polyps and tumors to low levels of two enzymes known as aPKCs. They showed that mice engineered to lack these aPKC enzymes in their gut linings reliably form serrated polyps and then aggressive tumors.

In the new study, the scientists found that in serrated-type tumors in these mice, and even in intestinal tissue poised to develop these types of cancerous lesions, cholesterol synthesis was strikingly upregulated, suggesting that cholesterol may be an early driver of tumor development.

The researchers revealed how the absence of aPKC enzymes, especially in metaplastic tumor cells, unleashes the activation of a transcription factor called SREBP2, which switches on cholesterol production. Tests on colorectal polyp and tumor samples from human patients dovetailed with the mouse findings. They found, for example, that only serrated-type tumors had low aPKC levels concomitant with the accumulation of SREBP2, a driver and a marker of upregulated cholesterol biosynthesis in the serrated cancer cells.

Lastly, the researchers tested a combination of two cholesterol synthesis-blocking drugs, including the widely used atorvastatin. The treatment, delivered when the low-aPKC mice were still quite young, significantly lowered the rate at which both serrated polyps and tumors later formed—and the serrated-type tumors that did form were less aggressive than those normally arising in the untreated mice.

The results indicate that targeting cholesterol could be a viable strategy for treating and preventing serrated-type colorectal tumors. The Moscat and Diaz-Meco labs are now hoping to set up an initial clinical trial of a cholesterol-lowering intervention in patients from whom serrated colorectal polyps have been removed.

“Currently when these polyps are detected early with colonoscopy, they are removed and patients have to hope that they don’t come back,” Dr. Moscat said. “In the future, we hope to have a more active method to prevent this very aggressive form of cancer before it is fully developed and more difficult to treat.”