Ultrasonographic evaluation of palatoglossal space may predict difficult mask ventilation: Study

Recent study explores the use of Modified Mallampati grading (MMG), ultrasonography at the submandibular region, and tongue thickness (TT) to predict difficult mask ventilation (DMV) and difficult laryngoscopy (DL). Unanticipated difficult mask ventilation has a high incidence rate despite various predictors for anticipating it, highlighting the need for accurate assessments. MMG and ultrasonography are discussed as potential tools to visualize airway structures and predict airway closure. The study involved adult patients undergoing elective surgery under general anesthesia, where the submandibular region was assessed using ultrasonography to measure palatoglossal space (PGS) and tongue thickness. PGS was significantly associated with DMV, with an area under the curve (AUC) of 0.989, indicating its high predictive value. A PGS cut-off value of 6.8 mm had a sensitivity of 94.4% in predicting DMV, making it a valuable tool for airway assessment.

Assessment of Tongue Thickness and Palatoglossal Space in Predicting Difficult Mask Ventilation

Tongue thickness was also assessed, with a cut-off value of 41 mm showing specificity but limited sensitivity in predicting DMV. The study emphasizes the simplicity and effectiveness of assessing PGS compared to obtaining dimensions, highlighting its utility as a rapid point-of-care ultrasound tool for predicting DMV. Additionally, the study compared PGS and TT in predicting both DMV and DL, providing insights into their respective sensitivities and specificities. The findings showed that an obliterated PGS had high sensitivity in predicting DL, indicating its potential as a robust predictor for airway difficulties.

Utility of Palatoglossal Space and Tongue Thickness in Predicting Airway Difficulties

The research also discusses previous studies that attempted to create scoring systems for identifying DMV but notes the challenges of using multiple parameters in assessments. Instead, the study suggests that PGS could serve as a valuable single parameter for predicting DMV due to its high sensitivity. The study concludes that PGS, alongside TT, can offer valuable insights into predicting airway difficulties during procedures requiring mask ventilation and laryngoscopy. Overall, the use of PGS and TT through ultrasonography presents promising avenues for enhancing the prediction of difficult airway management in clinical practice.

Key Points

– Modified Mallampati grading (MMG), ultrasonography at the submandibular region, and tongue thickness (TT) were studied to predict difficult mask ventilation (DMV) and difficult laryngoscopy (DL) in adult patients undergoing elective surgery.

– Ultrasonography was used to measure palatoglossal space (PGS) in the submandibular region, with PGS showing a significant association with DMV, indicated by an AUC of 0.989 and a sensitivity of 94.4% at a cut-off value of 6.8 mm.

– Tongue thickness was also assessed, but with limited sensitivity in predicting DMV, contrasting with the effectiveness of PGS assessment.

– An obliterated PGS was found to have high sensitivity in predicting DL, suggesting its potential as a robust predictor for airway difficulties.

– Previous studies used multiple parameters for DMV prediction, but this study suggests that PGS alone could be a valuable single parameter due to its high sensitivity.

– The study concludes that PGS, in combination with TT, offers valuable insights into predicting airway difficulties during procedures involving mask ventilation and laryngoscopy, showing promising avenues for improving difficult airway management predictions in clinical settings.

Reference –

Sekhar S, Kundra P, Mohan VK, Senthilnathan M, Ramesh A. Ultrasonographic evaluation of palatoglossal space to predict difficult mask ventilation – A prospective observational study. Indian J Anaesth 2025;69:315-8.

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Case of Knee joint synovial hemangioma treated with arthroscopic resection without hemarthrosis: A report

Intra-articular synovial hemangioma of the knee is a relatively rare benign tumor that if left undiagnosed and treated may be followed by degenerative cartilaginous changes and osteoarthritis. However, the non-specific symptoms of synovial hemangiomas limit its early diagnosis. Ryota Uemura et al reported their encounter with synovial hemangioma of the knee in which the diagnosis was based on a > 20-year history of chronic pain without joint swelling or hematoma. This case has been reported in line with the SCARE criteria in ‘International Journal of Surgery Case Reports.’

Case report

It describes a 34-year-old man who had experienced left knee joint pain since he was 14. He received symptomatic treatment at a chiropractic clinic each time he experienced the pain. However, the symptoms continued to recur even after 20 years, and the patient was referred to author’s hospital for examination. There was no history of trauma. At the time of examination, the range of motion of the left knee joint was good, and there were no obvious tumorous lesions on visual or palpation examinations. However, slight tenderness was observed at the upper edge of the patella. There was no pain at rest; however, he complained of pain at the patellar upper edge during squatting. Thigh circumference measurement revealed quadriceps femoris atrophy in the left leg (40.0 cm) compared to the right leg (43.0 cm). The authors suspected the presence of a discoid meniscus, intraarticular loose body, or intraarticular tumor and performed magnetic resonance imaging (MRI), which revealed a multilocular tumor formation on the patellar upper edge. CT scan revealed an unclear tumor in the patellar pouch, with no calcification or ossification inside the tumor. The bone cortex adjacent to the patellar upper edge was indistinct, and small bone-lucent areas were observed around it. Slightly sclerotic images were observed at the edge of the bone-lucent area, which suggested erosion. Based on these findings, pigmented villonodular synovitis was suspected.

The patient was provided with detailed information on the characteristics of the tumor and surgical treatment (arthroscopic excision or open excision). First, a portal was created on the outside of the patella. The joint was observed using arthroscopy and was shown to exhibit synovial hyperplasia. A tumorous lesion of approximately 20 mm in diameter was found, covered in fibrous tissue on the upper edge of the patella. Next, portals were created on the inside and outside of the upper patella and tumor excision was started. When an incision was made on the surface of the tumor using a sharp blade, synovium-like tissue with abundant blood flow was exposed from the inside. A shaver and a vaporizer were used to remove the tumor, expose the patellar ligament tissue, and confirm the upper edge of the patella. The tumor was observed to have infiltrated the patella bone; therefore, excavations were performed at the same site. After confirming that the entire tumor had been sufficiently excised, a portal was added on the inside of the patella, and the synovial tissue inside the joint was excised. No obvious arthritic changes were observed.

Histological examination revealed blood vessels of various sizes against a background of fibrous and adipose tissue. It had numerous vascular structures showing ERG positivity within the nodules with sclerotic changes, leading to the diagnosis of cavernous synovial hemangioma. At the 1-year follow-up, MRI revealed that the tumor was fully excised, with no signs of residual or recurrent tumors.

The authors concluded – “Accurate diagnosis and appropriate early treatment are necessary for synovial hemangiomas, similar to other tumors. In this case, the synovial hemangioma was not noted on follow-up MRI at 3 months or 1 year post-surgery. The patient’s clinical symptoms were relieved, and there was no recurrence even 1 year after the surgery. When a patient presents with recurrent knee joint pain, it is necessary to consider synovial hemangiomas as a differential diagnosis, even when knee joint swelling is absent.”

Further reading:

Knee joint synovial hemangioma treated with arthroscopic resection without hemarthrosis: A case report

Ryota Uemura et al

International Journal of Surgery Case Reports 116 (2024) 109352

https://doi.org/10.1016/j.ijscr.2024.109352

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Hallucinogen use linked to 2.6-fold increase in risk of death for people needing emergency care: Study

People seeking emergency care for hallucinogen use were at 2.6-fold higher risk of death within 5 years than the general population, according to a new study published in CMAJ.

The use of hallucinogens, such as ketamine, psychedelics, psilocybin, LSD, ayahuasca, and MDMA (Ecstasy), has rapidly increased since the mid-2010s, especially in Canada and the United States. In the US, the percentage of people reporting they used hallucinogens more than doubled from 3.8% in 2016 to 8.9% in 2021. “In Canada, an estimated 5.9% of people used a psychedelic such as LSD or psilocybin in 2023, with use as high as 13.9% in people aged 20–24,” says Dr. Daniel Myran, a family physician and public health and preventive medicine physician researcher with ICES, the Bruyère Health Research Institute, and The Ottawa Hospital.

Increasing use may partially reflect growing medical and societal interest in pairing psychedelics with psychotherapy for mental health and substance use disorders. However, although psychedelic-assisted therapy trials have generally been safe, there are few data about whether hallucinogens might increase the risk of adverse events, such as thoughts of suicide and death, when used outside of carefully controlled clinical trial settings or in populations currently excluded from trials.

“Despite the growing popularity of hallucinogen use, we know surprisingly little about potential adverse effects of hallucinogens, such as mortality risks. Contemporary clinical trials have not observed any short-term increase in risk of severe adverse events, including death, for trial participants. However, these studies involve careful supervision and therapy for trial participants and exclude people at high risk of adverse outcomes,” says Dr. Myran.

To better understand if there is an association between hallucinogen use and increased risk of death, researchers looked at health care data held by ICES on emergency department visits, hospitalizations, and outpatient physician visits for more than 11.4 million people in Ontario aged 15–105 years. Of the total group, 7954 (0.07%) sought acute care for hallucinogen use. The risk of death within 5 years for people who sought acute care for hallucinogen use was almost 10 times that of someone of the same age and sex in the general population. Individuals who received acute care for hallucinogen use had more medical comorbidities.

After accounting for other mental health conditions and substance use along with medical comorbidities (which were generally much more common in those using hallucinogens than the general population) people with acute care visits involving hallucinogens remained at elevated risk of death (2.6-fold higher).

People needing acute care for hallucinogen use were more likely to live in low-income neighbourhoods, to have been homeless at the time of a previous acute care visit, to be long-time residents of Canada, to have chronic health conditions, and/or to have received care for a mental health problem or substance use disorder in the previous 3 years. They were at higher risk of death than people who sought alcohol-related acute care, but at lower risk of death than people needing acute care for opioid or stimulant use.

“The findings highlight the need for ongoing investigation of and communication about both potential benefits and risks from hallucinogen use, particularly use outside clinical trial settings, given rapid increases in general population use,” says Dr. Marco Solmi, a psychiatrist at The Ottawa Hospital and associate professor, University of Ottawa.

Reference:

Daniel T. Myran, Jennifer Xiao, Nicholas Fabiano, Michael Pugliese, Tyler S. Kaster, Joshua D. Rosenblat, M. Ishrat Husain, Jess G. Fiedorowicz, Stanley Wong, Peter Tanuseputro and Marco Solmi, Mortality risk among people receiving acute hospital care for hallucinogen use compared with the general population, Canadian Medical Association Journal, DOI: https://doi.org/10.1503/cmaj.241191

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Johnson and Johnson Wins Rs 3.34 Crore Lawsuit Against Fake SURGICEL, ETHICON Sellers

New Delhi: The Delhi High Court has ruled in favor of Johnson & Johnson (J&J), awarding the company Rs 3.34 crore in damages against Medserve and its proprietor Pritamdas Arora, who were found guilty of counterfeiting and illegally selling J&J’s medical products, including those marketed under the ‘SURGICEL’ and ‘ETHICON’ trademarks.

Johnson & Johnson, through its subsidiary Ethicon, manufactures critical medical devices such as SURGICEL and ETHICON, widely used for wound closure and bleeding control in surgeries. However, in 2019, a neurosurgeon at the University of Kentucky Medical Center identified irregularities in a batch of SURGICEL products, which were later confirmed to be counterfeit.

Upon investigation, J&J traced the counterfeit medical products to M/s Medserve, a business operated by Pritamdas Arora in New Delhi. The counterfeit products were substandard, non-sterile, and contaminated, posing a severe risk to patient safety.

The Delhi High Court, presided over by Justice Amit Bansal, reviewed extensive evidence, including WhatsApp conversations, email correspondences, invoices, and financial transactions, confirming the defendants’ direct involvement in counterfeiting activities.

Justice Bansal emphasized the severity of the counterfeiting, stating;

“Counterfeiting of medical devices is not merely a case of trade mark infringement, it is a grave offence that endangers the lives of people. The defendants’ conduct demonstrates a deliberate effort to mislead the public, jeopardize consumer safety and exploit consumer trust for financial gain.”

The court highlighted that counterfeit medical products lacked essential sterility and quality standards required for surgical use. Further, the defendants falsified expiration dates on expired medical products, increasing the health risks for unsuspecting patients.

“The counterfeit products failed to meet the necessary oxidation levels required for proper absorption in the body. The use of such substandard medical devices during surgery could result in severe complications, including infections, foreign body reactions, and surgical adhesions.”

The court also criticized the impact of counterfeiting on J&J’s reputation, stating;

“The defendants’ deliberate and fraudulent acts have also caused irreparable harm to the plaintiff’s goodwill and market reputation. By selling substandard counterfeit products under the plaintiff’s trade marks, the defendants have misled consumers and associated the plaintiff’s name with the counterfeit goods.”

Taking a strict stance against counterfeiting, the court awarded Rs 2.34 crore as compensatory damages based on sales figures of counterfeit products and an additional Rs 1 crore as exemplary damages, citing the defendants’ deliberate and fraudulent actions.

Justice Bansal justified the award, noting;

“I am convinced with the evidence presented and submissions made by the counsel for plaintiff and conclude that a conservative profit margin of 25% can be assumed for awarding actual damages in favor of the plaintiff and against the defendants in the present case.”

“Counterfeit medical products are a direct threat to public health and safety. The defendants’ conduct demonstrates a deliberate effort to mislead consumers and exploit their trust for financial gain.”

The court-appointed Local Commissioner conducted raids on the defendants’ premises, seizing counterfeit ‘SURGICEL’ and ‘ETHICON’ products, along with falsified documentation, counterfeit labels, and substantial financial records.

The investigation revealed that the defendants laundered over Rs 9.39 crore through international transactions, diverting funds to multiple foreign bank accounts.

The court took serious note of the defendants’ refusal to cooperate, observing;

“The evidence presented before the Court, including invoices, bank receipts, and chat extracts, establishes without a doubt that defendant no. 1 has received substantial financial gains in the course of carrying out the infringing and counterfeiting activities.”

Despite multiple summons, the defendants failed to appear before the court, prompting the issuance of non-bailable warrants against Pritamdas Arora, who remained untraceable.

To prevent further consumer deception and safeguard public health, the court granted a permanent injunction restraining the defendants from using J&J’s trademarks, selling counterfeit products, or engaging in any activities that could mislead consumers into believing they were purchasing genuine J&J products.

The court also ordered the destruction of all counterfeit products seized during the proceedings, stating;

“The plaintiff is entitled to compensatory and exemplary damages, and the counterfeit products seized shall be destroyed to prevent further harm to the public.”

To view the original order, click on the link below:

https://medicaldialogues.in/pdf_upload/jjjudgment-278336.pdf

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Smoking Duration and Log Cig-Years Outperform Pack-Years in Predicting Survival in HNSCC: Study Finds

Canada: A recent cohort study published in JAMA Otolaryngology-Head & Neck Surgery evaluated the effectiveness of different smoking metrics in predicting overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC). The study identified smoking duration (aHR: 1.11) and log cig-years (aHR: 1.11) as the most reliable predictors of overall survival, demonstrating a strong linear correlation with OS and surpassing pack-years in predictive accuracy.

“Their effectiveness remained consistent across different patient subgroups and tumor sites, reinforcing their potential as superior metrics for assessing the impact of smoking on survival outcomes,” the researchers wrote.

Cigarette smoking plays a critical role in the development and prognosis of head and neck squamous cell carcinoma, significantly impacting patient survival. While smoking is a well-established risk factor, there is limited evidence on the most effective metric for accurately modeling its association with survival outcomes. Existing survival models often rely on smoking status or pack years to quantify exposure, but these measures may not fully capture the long-term effects of smoking.

To address this limitation, Andrew C. L. Lam, Department of Medicine, University of Toronto, Toronto, Ontario, Canada, and colleagues have explored alternative metrics that provide a more precise evaluation of smoking impact on survival in HNSCC patients.

For this purpose, the researchers conducted a retrospective multicenter cohort study across six clinical epidemiological studies, including five from the Human Papillomavirus, Oral and Oropharyngeal Cancer Genomic Research (VOYAGER) consortium. The study analyzed data from patients aged 18 and older with pathologically confirmed HNSCC, collected between January 2002 and December 2019 and evaluated between January 2022 and November 2024.

The primary outcome was overall survival (OS), assessed using eight smoking metrics, including pack-years, duration, and log cig-years. These metrics were compared based on their association strength in Cox proportional hazard models, linear trend significance, Akaike information criterion (AIC), and spline curve assessments. Secondary analyses explored OS across clinicodemographic subgroups and tumor subsites, while exploratory outcomes included cancer-specific and noncancer survival.

The following were the key findings:

  • The study included 8,875 patients with HNSCC, with a median age of 61 years and 24% female participants.
  • Among the eight smoking metrics evaluated, smoking duration (aHR: 1.11) and log cig-years (aHR: 1.11) had the highest adjusted hazard ratios (aHRs).
  • Both smoking duration and log cig-years showed a statistically significant linear association with overall survival.
  • Log cig-years demonstrated the best model fit, with the lowest Akaike information criterion (AIC) linear value and the most visually linear spline curve for OS modeling.
  • Smoking duration and log cig-years outperformed pack-years in predicting OS across all age groups, smoking statuses, and cancer stages.
  • Both metrics performed well in lip and oral cavity cancers, while duration alone showed significance in laryngeal cancer and human papillomavirus (HPV)-negative oropharyngeal cancers.
  • In an exploratory analysis, smoking duration had the highest aHR (1.15) for noncancer survival, while log cig-years had the lowest AIC linear value in modeling noncancer survival.

The researchers found that smoking duration and log cig-years demonstrated the strongest linear association with overall survival in patients with HNSCC, maintaining consistent predictive performance across various clinicodemographic subgroups and tumor subsites.

“While conventional survival models often rely on smoking status or pack-years to quantify smoking exposure, these findings suggest that duration and log cig-years may serve as superior metrics for assessing the impact of smoking on survival. Their robustness in modeling survival outcomes highlights their potential for both clinical decision-making and future research applications in HNSCC,” the researchers concluded.

Reference:

Lam ACL, Hueniken K, Pienkowski M, et al. Performance of 8 Smoking Metrics for Modeling Survival in Head and Neck Squamous Cell Carcinoma. JAMA Otolaryngol Head Neck Surg. Published online February 20, 2025. doi:10.1001/jamaoto.2024.5392

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Selumetinib shows Limited Efficacy in Treatment of cutaneous neurofibromatosis: JAMA

Researchers have found in a nonrandomised pilot trial that selumetinib showed a reduction in cutaneous neurofibromatosis volume, but it did not lead to sustained improvements in patient-reported outcomes.

Cutaneous neurofibromas (cNFs) can cause itching, disfigurement, pain, and emotional difficulties in people with neurofibromatosis type 1 (NF1). A study was done to determine the impact of the mitogen-activated protein kinase kinase inhibitor selumetinib on cNF including change in tumor volume and patient-reported outcome measures. Adults with NF1 and 9 or more measurable cNFs were enrolled in this nonrandomized pilot trial at the National Cancer Institute and the University of Alabama at Birmingham, which spanned from August 26, 2017, to August 21, 2023. Participants received selumetinib for up to 24 cycles (1 cycle = 28 days) with restaging visits after every 4 cycles. Photography and volumetric measurements of cNFs using calipers were used to evaluate the number and volume of tumors. Participants completed the Skindex-29 Quality of Life assessment to quantify the effect of treatment on symptoms, functioning, emotions, itching, and pain. Results Among the 11 participants who enrolled, the median (range) age was 54 (28-75) years, and 6 were female. The median (IQR) best response across all participants and tumors was a −28.5% (−40.9% to −12.5%) decrease in cNF volume from baseline. Some participants showed a visible improvement in cNF burden while receiving treatment in standardized photographs. The median (range) duration of treatment was 9 cycles (1-24), with only 4 participants completing the full 24 cycles of treatment. Two of these participants continued treatment beyond the original 24 cycles due to perceived clinical benefit. All participants experienced at least 1 reversible drug-related adverse event (AE), with cutaneous AEs such as dry skin and rash being the most common. Two participants were removed from treatment due to concern for drug reaction with eosinophilia and systemic symptoms. While the Skindex-29 assessment showed improvement in emotion scores after cycle 1, there were no other significant or durable changes in scores. In this nonrandomized pilot trial, selumetinib resulted in some decrease in cNF volume; however, there was no sustained improvement in patient-reported outcome measures. Study enrollment was incomplete, in part due to the COVID-19 pandemic, and highlights the challenges of treating patients with cNF with a drug that often leads to dermatologic AEs. Future larger studies using other measurement techniques, such as 3-dimensional photography, could help to yield results that are more generalizable to the phenotypically diverse NF1 population.

Reference:

Gross AM, Reid OH, Baldwin LA, et al. Treatment of Cutaneous Neurofibromas in Neurofibromatosis Type 1 With MEK Inhibitor Selumetinib: A Nonrandomized Clinical Trial. JAMA Dermatol. Published online February 26, 2025. doi:10.1001/jamadermatol.2024.6574

Keywords:

Selumetinib, shows, Limited, Efficacy, Treatment, cutaneous, neurofibromatosis, JAMA, Gross AM, Reid OH, Baldwin LA, JAMA Dermatology

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Lactation Consultant Interventions effective for promoting and supporting breastfeeding: JAMA

Researchers have found in a new study that Lactation consultant interventions significantly improve both exclusive breastfeeding and overall breastfeeding rates. The findings of the study have been published in JAMA.

By providing education, hands-on support, and problem-solving strategies, lactation consultants help mothers overcome challenges such as latching difficulties, low milk supply, and breastfeeding pain. Their guidance leads to increased breastfeeding duration and adherence to exclusive breastfeeding recommendations, benefiting both maternal and infant health.Breast milk offers numerous health benefits, yet breastfeeding recommendations are met less than half of the time in high-income countries. A study was done to evaluate the effect of lactation consultant (LC) interventions on breastfeeding, maternal breastfeeding self-efficacy, and infant growth compared to usual care. Data extracted included study design, participant and intervention characteristics, and outcome data. To account for studies that reported outcomes at multiple time points, effect estimates were pooled with 3-level correlated and hierarchical effects models. Meta-regression was performed for clinically important characteristics, such as the time point when the outcome was measured, intervention intensity, and participant income. The primary outcome was stopping exclusive breastfeeding. Secondary outcomes included stopping any breastfeeding, exclusive breastfeeding and any breastfeeding duration, maternal breastfeeding self-efficacy, infant overweight and obesity, and infant growth. Results The search yielded 6476 records, of which 40 studies were included involving 8582 participants. Studies were published between 1992 and 2024, and most studies (n = 22) were conducted in the US. Compared to usual care, LC interventions reduced the risk of stopping exclusive breastfeeding (risk ratio [RR], 0.96; 95% CI, 0.94-0.99) and any breastfeeding (RR, 0.92; 95% CI, 0.87-0.96) and increased any breastfeeding duration by 3.63 weeks (95% CI, 0.13-7.12). There was weak evidence that LC interventions increased exclusive breastfeeding duration (mean difference [MD], 1.44 weeks; 95% CI, −2.73 to 5.60), maternal breastfeeding self-efficacy (MD, 2.83; 95% CI, −1.23 to 6.90), or the risk of infant overweight and obesity (RR, 1.52; 95% CI, 0.94-2.46). Meta-regression showed that LC interventions were more effective at reducing the risk for stopping exclusive breastfeeding (P = .01) and any breastfeeding (P < .001) the earlier that breastfeeding was measured in the postpartum period. LC interventions with a higher intensity (ie, number of LC visits) were more effective at reducing the risk for stopping any breastfeeding (P = .04). According to the results of this systematic review and meta-analysis, LC interventions are a promising intervention for improving exclusive breastfeeding and any breastfeeding in high-income countries.

Reference:

D’Hollander CJ, McCredie VA, Uleryk EM, et al. Breastfeeding Support Provided by Lactation Consultants: A Systematic Review and Meta-Analysis. JAMA Pediatr. Published online March 03, 2025. doi:10.1001/jamapediatrics.2024.6810

Keywords:

Lactation, Consultant, Interventions, effective, promoting, supporting, breastfeeding, JAMA, D’Hollander CJ, McCredie VA, Uleryk EM, JAMA Pediatrics

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Promising new class of antimalarial drugs discovered

Innovative research approaches are therefore urgently needed to achieve long-term progress in prevention and treatment.

Malaria is caused by parasites of the genus Plasmodium, which is transmitted to humans through the bite of infected mosquitoes.

Plasmodium falciparum, the deadliest of the malaria species, has a highly complex life cycle controlled by precise gene regulation.

Understanding these regulatory processes is crucial in order to specifically combat the pathogen at different stages of development.

The team identified the chromatin remodeler PfSnf2L (a protein complex that regulates the accessibility of DNA for transcription) as a key regulator of genes that play an important role in various stages of the pathogen’s development.

“Our research shows that PfSnf2L is essential for P. falciparum to dynamically adjust gene expression,” explains Maria Theresia Watzlowik, lead author of the study.

“The unique sequence and functional properties of PfSnf2L led to the identification of a highly specific inhibitor that only kills Plasmodium falciparum,” explains Gernot Längst, Professor of Biochemistry at the University of Regensburg.

“This inhibitor represents a new class of antimalarials, potentially targeting all life cycle stages,” adds Professor Markus Meißner, Chair Professor of Experimental Parasitology at LMU’s Faculty of Veterinary Medicine.

“Malaria is one of the most adaptive diseases we face,” observes Längst.

Targeting its epigenetic regulation could pave the way for increasing the effectiveness of existing drugs, for example, or preventing the development of resistant parasites.

“The study underscores the importance of integrating epigenetics into malaria research. Future work will focus on testing small molecules that inhibit the parasite’s epigenetic machinery and exploring their effectiveness in preclinical models,” concludes Meißner.

In addition to scientists from LMU and the University of Regensburg, researchers from the University of Zurich (Switzerland), Pennsylvania State University (United States), and the University of Glasgow (United Kingdom) were involved in the study, which was supported by the German Research Foundation (DFG).

 Reference: Maria Theresia Watzlowik, Elisabeth Silberhorn, Sujaan Das, Ritwik Singhal, Kannan Venugopal, Simon Holzinger, Barbara Stokes, Ella Schadt, Lauriane Sollelis, Victoria A. Bonnell, Matthew Gow, Andreas Klingl, Matthias Marti, Manuel Llinás, Markus Meissner, Gernot Längst. Plasmodium blood stage development requires the chromatin remodeller Snf2L. Nature, 2025; DOI: 10.1038/s41586-025-08595-x

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Common gynaecological disorders linked to raised heart and cerebrovascular disease risk: Study

Having one or more common gynaecological disorders, such as endometriosis or heavy or irregular periods, may be linked to a heightened risk of heart disease and conditions that affect blood flow to the brain (cerebrovascular disease), finds a pooled data analysis of the available evidence published online in the journal Heart.

Although the quality of the studies included in the analysis was variable, the researchers nevertheless conclude that clinicians and the public need to be more aware of these associations to potentially mitigate the risks.

Long term non-cancerous gynaecological disorders are common and include polycystic ovary syndrome (PCOS), endometriosis (where tissue similar to the womb lining grows outside of the womb), adenomyosis (where the womb lining grows into the muscular wall), uterine fibroids, primary dysmenorrhoea (painful menstrual cramps), chronic pelvic pain, irregular and/or very heavy periods, and abnormal uterine bleeding, explain the researchers.

These disorders significantly affect women’s health and wellbeing. And previously published research indicates that they may be associated with cardiovascular or cerebrovascular disease, they add.

To explore this further, the researchers scoured research databases looking for relevant studies published up to April 2024. From an initial haul of 59 studies, 28, involving 3,271,242 women, were eligible for systematic review and inclusion in the pooled data analysis.

Only endometriosis, polycystic ovary syndrome, heavy periods, and irregular menstrual cycles featured in the studies included in the analysis.

Overall, the pooled data analysis of the study results showed that compared with people without one of these conditions, those who had at least one had a significantly (28%) higher risk of cardiovascular and cerebrovascular disease.

Specifically, their risk of ischaemic heart disease was 41% higher, while their risk of cerebrovascular disease alone was 33% higher.

Further analysis indicated that the overall risk of cardiovascular and cerebrovascular disease and each of its components was higher among those with a history of endometriosis or polycystic ovary syndrome.

The researchers caution that the design and methodology of the included studies varied considerably, and over half (53.5%) of the studies were scored as having a very high risk of bias, largely because of the lack of adequate consideration of potentially influential factors.

And several aspects of cardiovascular disease weren’t covered by the included studies, such as atrial fibrillation (abnormal heart rhythm).

But the researchers nevertheless suggest that there may be plausible biological pathways linking cardiovascular and cerebrovascular disease and common gynaecological disorders, including systemic inflammation and oestrogen production.

There may also be an overlap between gynaecological risk factors and cardiovascular risk factors, they suggest, pointing out that metabolic syndrome is often present in people with polycystic ovary syndrome, for example.

“The association between [cardiovascular and cerebrovascular disease] and [common gynaecological disorders] requires further exploration with high-quality longitudinal studies adjusted for confounders to establish temporal relationships and causality,” they emphasise.

But they nevertheless conclude: “Although the extent of this association is still to be explored, and causality has not been established, the findings suggest that it is important to raise awareness of the potential association…. both in the general public and healthcare professionals.

“Awareness of this association would allow healthcare professionals to advise patients regarding risk-reducing behavioural changes and interventions, to potentially prevent or delay the onset of, or reduce the severity of cardiovascular and cerebrovascular disease.”

Reference:

Non-malignant gynaecological disease and risk of cardiovascular or cerebrovascular disease: a systematic review and meta-analysis. Heart. DOI: 10.1136/heartjnl-2024-324765

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Brain plays central role in development of obesity, suggests research

The number of obese persons has grown significantly in recent decades, which presents significant difficulties for those who are impacted, healthcare systems, and those who provide treatment. The hormone insulin plays a key role in the development of obesity. Up until recently, there have been numerous signs indicating insulin causes neurodegenerative and metabolic disorders, especially in the brain. A recent study by the University Hospital of Tübingen, the German Center for Diabetes Research (DZD), and Helmholtz Munich offers intriguing new insights into the origins of type 2 diabetes and obesity as well as the brain’s function as a critical control center.

Obesity has only been officially recognized as a disease in Germany since 2020, despite the fact that it has long been known to cause a number of illnesses, including diabetes, heart attacks, and even cancer. The World Health Organization has already declared obesity to be an epidemic, affecting over one billion individuals globally and almost 16 million in Germany alone. A body mass index of 30 or more is considered obese, and a poor diet and insufficient exercise are frequently cited as the causes of this chronic illness. However, the mechanisms in the body that lead to obesity and cause the disease are more complex.

Obesity and the role of insulin in the brain

Unhealthy body fat distribution and chronic weight gain are linked to the brain’s sensitivity to insulin. What specific functions does insulin perform in the brain, and how does it affect individuals of normal weight? In their study, Prof. Dr. Stephanie Kullmann and her colleagues at the Tübingen University Hospital for Diabetology, Endocrinology, and Nephrology found the answer to this query. “Our findings demonstrate for the first time that even a brief consumption of highly processed, unhealthy foods (such as chocolate bars and potato chips) causes a significant alteration in the brain of healthy individuals, which may be the initial cause of obesity and type 2 diabetes,” says Prof. Kullmann, the study’s leader. In a healthy state, insulin has an appetite-suppressing effect in the brain. However, in people with obesity in particular, insulin no longer regulates eating behavior properly, resulting in insulin resistance. “Interestingly, in our healthy study participants, the brain shows a similar decrease in sensitivity to insulin after a short-term high calorie intake as in people with obesity,” says Ms. Kullmann. “This effect can even be observed one week after returning to a balanced diet,” she adds. She is also deputy head of the Metabolic Neuroimaging department at the DZD partner Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen.

Focus on the brain

Prof. Dr. Andreas Birkenfeld, Medical Director of Internal Medicine IV, Director of the IDM and DZD Board Member, and the study’s final author, concludes, “We assume that the brain’s insulin response adapts to short-term changes in diet before any weight gain occurs and thus promotes the development of obesity and other secondary diseases.” He urges more research on how the brain contributes to the development of obesity and other metabolic illnesses in light of the current findings.

Short period with far-reaching effects

29 male volunteers of average weight participated in the study and were split into two groups. For five days in a row, the first group had to supplement their regular diet with 1500 kcal from highly processed, high-calorie snacks. The extra calories were not consumed by the control group. Both groups underwent two separate examinations following an initial evaluation. One examination was conducted immediately following the five-day period, and another was conducted seven days after the first group had resumed their regular diet. The researchers used magnetic resonance imaging (MRI) to look at the liver’s fat content and the brain’s insulin sensitivity. Not only did the fat content of the liver of the first group increase significantly after five days of increased calorie intake. Surprisingly, the significantly lower insulin sensitivity in the brain compared to the control group also persisted one week after returning to a normal diet. This effect had previously only been observed in obese people.

Reference:

Stephanie Kullmann, Lore Wagner, Robert Hauffe, Anne Kühnel, Leontine Sandforth, Ralf Veit, Corinna Dannecker, Jürgen Machann, Andreas Fritsche, Nobert Stefan, Hubert Preissl, Nils B. Kroemer, Martin Heni, André Kleinridders, Andreas L. Birkenfeld. A short-term, high-caloric diet has prolonged effects on brain insulin action in men. Nature Metabolism, 2025; DOI: 10.1038/s42255-025-01226-9

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