ONCOLOGY

Metalloproteinases include a disintegrin and metalloprotease (ADAM), which were previously examined using a fluorescence assay system and described their association with resistance to systemic therapy in cancer patients. Inhibiting their immunomodulating activity in chronic inflammation restores innate immunity and potentially prevents the development of various cancers. This review summarizes our current understanding of the role of ADAMs in gastroenterological diseases with regard to the immune system. In addition, several Food and Drug Administration (FDA) approved inhibitors of ADAMs have been identified, and potential therapies for targeting ADAMs in treating chronic inflammatory diseases and cancers are discussed.

ADAMs in Gastroenterological Diseases: Role in Immune System and Potential Therapies

UROLOGY

Gonadotropin therapy restored sperm production in 74% and supported pregnancy in 52% of couples with male hypogonadism.

Gonadotropin Therapy Boosts Fertility in Male Hypogonadism

A systematic review of 50 studies involving 1,583 men with hypogonadotropic hypogonadism and azoospermia found that gonadotropin therapy induced spermatogenesis in 74% of patients, with sperm production taking about 12 months on average. Pregnancy occurred in 52% of couples, while combined gonadotropin therapy outperformed hCG alone.

GASTROENTEROLOGY

UDFF accurately detected liver steatosis in children, offering a non-invasive approach for MASLD screening and monitoring.

UDFF Shows High Accuracy for Detecting MASLD in Children

A prospective study of 70 children found that ultrasound-derived fat fraction (UDFF) closely matched MRI-PDFF for detecting liver steatosis. UDFF showed strong correlation with MRI-PDFF and achieved 97.6% sensitivity and 92.9% specificity for detecting steatosis, supporting its potential as a non-invasive, reproducible tool for screening, staging, and monitoring paediatric MASLD.

Baseline testosterone did not predict the severity of body composition, physical, energy or sexual changes during ADT.

Baseline Testosterone Does Not Predict ADT Side Effects

A study of 39 men receiving 24 weeks of androgen deprivation therapy (ADT) for prostate cancer found substantial increases in fat mass and declines in lean mass, physical function, energy, and sexual desire. However, pretreatment testosterone levels were not associated with the severity of these changes, suggesting baseline testosterone does not predict ADT-related adverse effects.

One year of GAHT increased upper-body strength in transmasculine people but reduced strength and power in transfeminine people.

GAHT Changes Upper-Body Muscle Strength and Power

A prospective study of 92 transgender people found that 1 year of gender-affirming hormone therapy produced opposite changes in upper-body muscle performance. Maximal strength increased by 12% in treatment-naïve transmasculine participants, while it decreased by 23% in treatment-naïve transfeminine participants, accompanied by a 23% reduction in muscle power.

PSYCHIATRY

Earlier puberty timing was linked to subtle differences in memory, learning and executive functioning in adolescents.

Earlier Puberty Linked to Differences in Cognitive Performance

A study of 10,722 adolescents from the ABCD cohort found that earlier puberty timing was associated with poorer performance in memory and learning tasks in both girls and boys, with additional effects on list sorting in boys. Mendelian randomization supported a link between later menarche and better executive functioning, although the observed effect sizes were small.

NEUROLOGY

Behavioral disorders predicted earlier care home admission and shorter survival in people with semantic dementia.

Behavioral Disorders Predict Outcomes in Semantic Dementia

A 31-year cohort study of 90 people with semantic dementia found that behavioral disorders were the only baseline factor predicting earlier loss of independence. Half of patients entered a care home 7.5 years after diagnosis and half died after 8.4 years, while even mild behavioral symptoms were associated with earlier admission and shorter survival.

A study of 83,159 adults found major population differences in links between cardiovascular disease and cognitive decline.

Cardiovascular Disease and Cognitive Decline Show Global Differences

A pooled analysis of 83,159 adults aged 50 years and older across five multinational cohorts found substantial differences in the association between cardiovascular disease and cognitive decline. Heart disease was linked to faster cognitive decline in four Western cohorts, while stroke alone showed no significant association, highlighting important population-level differences.

Problematic media and social media use may contribute to worsening mental health problems during early adolescence.

Problematic Media Use Linked to Mental Health Problems in Youth

A longitudinal study of 6,026 early adolescents found that mental health problems predicted later problematic media and social media use, which in turn were associated with worsening mental health over three years. Exposure to potentially traumatic events independently contributed to problematic media use but did not alter the relationship between media use and mental health outcomes.

Operative time ≥95 minutes was linked to higher postoperative complication risk after PCNL in older adults.

PCNL Operative Time and Complication Risk in Older Adults

An international multicentre study of 716 patients aged ≥70 years undergoing percutaneous nephrolithotomy (PCNL) found that operative time ≥95 minutes was independently associated with higher odds of overall, major, and infectious complications. Risk increased more sharply beyond 90–100 minutes, highlighting operative duration as a potential marker for intraoperative risk stratification.

Higher SII was associated with SSNHL and poorer hearing recovery, suggesting potential prognostic value.

Systemic Immune-Inflammation Index Linked to SSNHL

A systematic review and meta-analysis of 11 studies involving 1,263 participants found significantly higher systemic immune-inflammation index (SII) levels in patients with sudden sensorineural hearing loss (SSNHL) than in healthy controls. Among SSNHL patients, lower SII was associated with hearing recovery, suggesting SII may have potential as a marker of disease occurrence and prognosis.

RHEUMATOLOGY

Real-world secukinumab use was associated with remission and reduced glucocorticoid exposure in patients with GCA.

Secukinumab Shows Real-World Activity in Giant Cell Arteritis

A multicentre Italian study of 36 patients with giant cell arteritis (GCA), most with relapsing disease and prior biologic exposure, found clinical remission in 83.3% at 12 months. Glucocorticoid use also declined substantially, with 40% achieving GC-free remission. Adverse events occurred in 55.6%, including infections in 50.0%. Further prospective evaluation is warranted.

CARDIOLOGY

Quality of life improved after heart transplantation and mechanical circulatory support in older patients with heart failure.

Quality of Life After Heart Transplantation or Mechanical Support

A multicentre US study of 305 older adults undergoing advanced heart failure therapy found that health-related quality of life improved after heart transplantation and long-term mechanical circulatory support. Improvements were generally sustained through 24 months, although patients receiving long-term mechanical support had lower quality-of-life scores over time than those undergoing transplantation without pretransplant support.

FAERS analysis identified 42 drugs potentially associated with male hypogonadism, including several with no label warnings.

42 Drugs Linked to Male Hypogonadism in FAERS Analysis

An analysis of FDA Adverse Event Reporting System data from 2004 to 2024 identified 42 drugs across 10 therapeutic classes with signals for male hypogonadism. Bayesian analysis classified 6 drugs as high risk and 11 as medium risk. Notably, 20 drugs lacked male hypogonadism warnings on their labels, including 3 classified as high risk.

Short cervical length may help identify PAS pregnancies at higher risk of early delivery and maternal and neonatal complications.

Cervical Length May Predict Delivery Risk in Placenta Accreta

A prospective study of 41 women with placenta accreta spectrum (PAS) found that cervical length below 25 mm at 28 and 32 weeks was associated with delivery by 34 weeks, higher rates of Cesarean hysterectomy, and more emergency Cesarean deliveries. Short cervical length was also linked to greater neonatal respiratory and resuscitation needs.

A global survey found major differences in MAS treatment, driven by disease context, geography and access to immunomodulatory drugs.

Global Differences in Macrophage Activation Syndrome Treatment

An international survey of 287 physicians from 64 countries found substantial variation in the treatment of macrophage activation syndrome (MAS). Intravenous methylprednisolone remained the most commonly used first-line therapy, while anakinra, ciclosporin, and IVIG were frequently added. Differences in drug availability, particularly for anakinra and emapalumab, strongly influenced treatment choices.

The immunological role of...

The immunological role of ADAMs in the field of gastroenterological chronic inflammatory diseases and cancers: a review