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A new study published in The New England Journal of Medicine showed that bevacizumab and erlotinib together demonstrated efficacy in individuals with spontaneous or Hereditary leiomyomatosis and renal-cell cancer (HLRCC)-associated papillary renal-cell carcinoma.

Germline mutations in fumarate hydratase (FH) cause the genetic disease known as hereditary leiomyomatosis and renal cell cancer syndrome. Skin leiomyomas, early-onset numerous uterine leiomyomas, and an aggressive form of type 2 papillary renal cell carcinoma (RCC) are the hallmarks of this autosomal dominant disorder. The WHO has modified its 2016 genitourinary cancer classification, including RCC in HLRCC as a new entity, HLRCC-associated RCC, even though RCC developing in HLRCC syndrome had previously been classified as type 2 papillary RCC.

The patients with severe HLRCC-associated papillary renal-cell carcinoma have no known therapeutic treatment, and the majority of them pass away as their condition worsens. Thus, this research evaluated the effectiveness of using bevacizumab and erlotinib in combination to treat HLRCC.

This research assessed the effectiveness of erlotinib (150 mg once daily) and bevacizumab (10 mg per kilogram of body weight every two weeks) in patients with advanced HLRCC-associated or spontaneous papillary renal-cell carcinoma. Overall response was the main outcome, while progression-free and overall survival were the secondary outcomes.

40 patients with spontaneous papillary renal-cell carcinoma and 40 patients with HLRCC-associated papillary renal-cell carcinoma were included in the study. Nearly, 31 patients (72%; 95% CI, 57 to 83) with HLRCC-associated papillary renal-cell carcinoma experienced a confirmed response; the median overall survival was 44.6 months (95% CI, 32.7 to could not be estimated) and the median progression-free survival was 21.1 months (95% CI, 15.6 to 26.6).

With a median progression-free survival of 8.9 months (95% CI, 5.5 to 18.3) and a median overall survival of 18.2 months (95% CI, 12.6 to 29.3), 14 patients (35%; 95% CI, 22 to 51) with sporadic papillary renal-cell carcinoma experienced a verified response.

The most frequent side effects of therapy were proteinuria (78%), diarrhea (89%), and acneiform rash (93%). And the most frequent adverse events of grade 3 or above that were associated to therapy were proteinuria (17%) and hypertension (34%). Overall, a combination of bevacizumab and erlotinib demonstrated anticancer efficacy in patients with HLRCC-associated or spontaneous papillary renal-cell carcinoma. 

Reference:

Srinivasan, R., Gurram, S., Singer, E. A., Sidana, A., Al Harthy, M., Ball, M. W., Friend, J. C., Mac, L., Purcell, E., Vocke, C. D., Ricketts, C. J., Kong, H. H., Cowen, E. W., Malayeri, A. A., Shih, J. H., Merino, M. J., & Linehan, W. M. (2025). Bevacizumab and erlotinib in hereditary and sporadic papillary kidney cancer. The New England Journal of Medicine, 392(23), 2346–2356. https://doi.org/10.1056/NEJMoa2200900

Insulin resistance detected by routine triglyceride-glucose (TyG) index can flag people with early Alzheimer’s who are four times more likely to present rapid cognitive decline, according to new research presented at the European Academy of Neurology (EAN) Congress 2025.

Neurologists at the University of Brescia reviewed records for 315 non-diabetic patients with cognitive deficits, including 200 with biologically confirmed Alzheimer’s disease. All subjects underwent an assessment of insulin resistance using the TyG index and a clinical follow-up of 3 years. When patients were divided according to TyG index, those in the highest third of the Mild Cognitive Impairment AD subgroup deteriorated far more quickly than their lower-TyG peers, losing >2.5 points on the Mini Mental State Examination per year (hazard ratio 4.08, 95% CI 1.06–15.73). No such link appeared in the non-AD cohort.

“Once mild cognitive impairment is diagnosed, families always ask how fast it will progress”, said lead investigator Dr Bianca Gumina. “Our data show that a simple metabolic marker available in every hospital laboratory can help identify more vulnerable subjects who may be suitable candidates for targeted therapy or specific intervention strategies.”

While insulin resistance has been linked to the onset of Alzheimer’s disease, its role in how quickly the condition progresses has received less attention. This study aimed to fill that gap by focusing on its impact during the prodromal mild cognitive impairment (MCI) stage, when patients follow highly variable trajectories. The researchers used the TyG index, which offers a low-cost, routinely available surrogate for insulin resistance, to explore whether metabolic dysfunction could help predict the pace of cognitive decline after diagnosis.

In AD specifically, insulin resistance is believed to impair neuronal glucose uptake, promote amyloid accumulation, disrupt the blood–brain barrier, and fuel inflammation – pathways that are less relevant or differently regulated in other neurodegenerative diseases.

“We were surprised to see the effect only in the Alzheimer’s spectrum and not in other neurodegenerative diseases”, Dr Gumina noted. “It suggests a disease-specific vulnerability to metabolic stress during the prodromal window, when interventions may still change the trajectory.”

The researchers at University of Brescia, led by Professor Padovani and Professor Pilotto, found that high TyG was also associated with blood–brain barrier disruption and cardiovascular risk factors, yet it showed no interaction with the APOE ε4 genotype, indicating that metabolic and genetic risks may act through distinct pathways.

Identifying high-TyG patients could refine enrolment for anti-amyloid or anti-tau trials and prompt earlier lifestyle or pharmacological measures to improve insulin sensitivity. The researchers are currently investigating whether TyG levels also track with neuroimaging biomarkers to aid earlier detection and stratification.

“If targeting metabolism can delay progression, we will have a readily modifiable target that works alongside emerging disease-modifying drugs”, concluded Dr Gumina.

Reference:

Simple blood test predicts cognitive decline in Alzheimer’s patients, new study shows, Beyond, Meeting: European Academy of Neurology (EAN) Congress 2025.

A new study published in the Annals of Internal Medicine showed that fecal microbiota transplant (FMT) was noninferior to vancomycin as a first-line treatment for Clostridioides difficile infection. FMT showed slightly higher cure rates without recurrence and comparable safety. Experts suggest that microbiota therapy could reduce antibiotic use, though its widespread adoption as initial treatment remains uncertain.

The most frequent cause of healthcare-associated diarrhea is Clostridioides difficile (formerly known as Clostridium) infection (CDI), which has a high mortality and recurrence rate. Additionally, treating recurring cases might be difficult. While fecal microbiota transplantation is advised for recurrent CDI, its function in initial CDI is not well understood. Thus, this study by Frederik Emil Juul and team looked in to the safety and effectiveness of FMT in primary CDI.

This study was conducted mostly in Norwegian hospitals and primary care centers. The main criteria were adults with CDI (defined as C. difficile toxin in stool and ≥3 loose stools per day) and no prior CDI within 365 days prior to recruitment. FMT without antibiotic pretreatment was compared to oral vancomycin, 125 mg four times a day for 10 days, as part of the intervention. Clinical cure (firm stools or <3 bowel movements per day) at day 14 and no illness recurrence within 60 days with the prescribed medication alone were the main endpoints.

100 of the 104 randomly assigned patients were eligible for analysis after receiving FMT or the initial dose of vancomycin. Nearly, 34 out of 51 patients (66.7%) who received FMT and 30 out of 49 (61.2%) who received vancomycin experienced clinical cure and no disease recurrence within 60 days without further treatment (difference, 5.4 percentage points [95.2% CI, −13.5 to 24.4 percentage points]; P for noninferiority < 0.001, denying the hypothesis that response to FMT is 25 percentage points lower than response to vancomycin).

4 patients in the vancomycin group and 11 in the FMT group received extra C difficile therapy. At day 14, 40 out of 51 patients (78.4%) with FMT and 30 out of 49 (61.2%) with vancomycin showed clinical cure and no recurrence with or without continued therapy (difference, 17.2 percentage points [95.2% CI, −0.7 to 35.1 percentage points]). 

Overall, FMT demonstrated similar safety and marginally greater cure rates without recurrence. Although its broad usage as a first line of treatment is yet unknown, experts point out that microbiota therapy may lessen the need for antibiotics. For primary CDI, FMT can be regarded as the first-line treatment.

Reference:

Juul, F. E., Bretthauer, M., Johnsen, P. H., Samy, F., Tonby, K., Berdal, J. E., Hoff, D. A. L., Ofstad, E. H., Abraham, A., Seip, B., Wiig, H., Rognstad, Ø. B., Glad, I. F., Valeur, J., Nissen-Lie, A. E., Ness-Jensen, E., Lund, K. M. A., Skjevling, L. K., Hanevik, K., … Garborg, K. K. (2025). Fecal Microbiota transplantation versus vancomycin for primary Clostridioides difficile infection : A randomized controlled trial. Annals of Internal Medicine. https://doi.org/10.7326/ANNALS-24-03285