Approximately 40% of patients with chronic kidney disease (CKD) experience cognitive impairment (CI), which is strongly associated with increased mortality. CI is driven by multiple factors, including vascular injury, accumulation of uremic toxins, disruption of the blood–brain barrier, and chronic inflammation. Recent evidence suggests that kidney disease and neurocognitive decline are mechanistically linked through dysregulated tryptophan metabolism. Tryptophan is metabolised through three main pathways: the kynurenine, indole, and serotonin pathways, each producing bioactive metabolites with distinct neurophysiological effects. The hallmarks of CKD include chronic inflammation, gut microbial dysbiosis, and impaired renal clearance, all of which alter tryptophan metabolism. Inflammation drives tryptophan metabolism towards the kynurenine pathway, increasing the formation of neurotoxic compounds that promote oxidative stress, excitotoxicity, and neuronal injury. However, reduced availability of tryptophan for serotonin synthesis impairs serotonergic signalling and neurotransmission, as well as melatonin biosynthesis, thereby contributing to circadian rhythm disturbances and impaired glymphatic clearance. Concurrently, gut dysbiosis and reduced renal clearance promote the accumulation of indole-derived uremic toxins, leading to endothelial dysfunction, neuroinflammation, and disruption of the blood–brain barrier. This review highlights the current evidence of dysregulated tryptophan metabolism in CKD and its impact on the pathogenesis of neurocognitive complications. The review also discusses potential biomarkers and therapeutic strategies, including kynurenine pathway inhibitors, gut microbiota modulation, uremic toxin adsorption, melatonin supplementation and personalised medicine to mitigate cognitive impairment in CKD.
Pharmacotherapy, acupoint stimulation, and psychotherapy for perimenopausal women with anxiety, depression, and panic disorder: a systematic review and network meta-analysis of randomized controlled trials
BackgroundPerimenopausal women frequently experience physiological and psychological symptoms, including anxiety, depression, and panic disorders, mainly due to declining ovarian function and hormonal changes. Current options include pharmacotherapy, acupoint stimulation (AcuStim), and psychotherapy (psych), but their comparative efficacy and safety remain controversial.ObjectiveThis network meta-analysis (NMA) systematically compared pharmacotherapy, AcuStim, and psychotherapy for perimenopausal anxiety, depression, and panic disorder, assessing clinical efficacy, adverse events (AEs), and changes in the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Kupperman Index (KI), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), Pittsburgh Sleep Quality Index (PSQI), and serum hormone levels.MethodsWe searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and SinoMed from inception to June 14, 2026, for randomized controlled trials (RCTs). A Bayesian NMA was performed, and the Surface Under the Cumulative Ranking Curve (SUCRA) was calculated.ResultsThe study included 131 RCTs, encompassing 11457 perimenopausal women diagnosed with emotional disorders. These trials evaluated three distinct treatment strategies. The NMA showed that the highest SUCRA probabilities were observed for drug_psych across HAMD (SUCRA = 92.4%), KI (SUCRA = 97.9%), SDS (SUCRA = 94.5%), PSQI (SUCRA = 98.1%), and follicle-stimulating hormone (FSH) (SUCRA = 96.1%) reduction and estradiol (E2) (SUCRA = 0.1%) elevation; for AcuStim_psych (SUCRA = 93.7%) in HAMA reduction; for psych (SUCRA = 98.9%) in SAS reduction; for drug_AcuStim in clinical efficacy (SUCRA = 9.0%) and luteinizing hormone (LH) reduction (SUCRA = 100%); and for control (SUCRA = 65.5%) in safety outcomes. In pharmacotherapy subgroup analyses, antidepressants (ADs)_Traditional Chinese medicine (TCM) ranked highest for HAMD (SUCRA = 87.2%) and safety (SUCRA = 82%), ADs_antipsychotics (AP) (SUCRA = 97.5%) for HAMA, and ADs_hormone replacement therapy (HRT) (SUCRA = 10.2%) for clinical efficacy.ConclusionPharmacological, acupoint stimulation, and psychological interventions each demonstrated therapeutic benefits for perimenopausal women with emotional disorders. Combination therapies generally showed more favorable efficacy across multiple psychological and endocrine outcomes than single-modality interventions, while no single treatment strategy was consistently superior across all outcomes. These findings may provide evidence to support individualized treatment selection according to patients’ clinical characteristics and therapeutic goals.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261340530.
An AI co-scientist to accelerate biomedical research
Nature Medicine, Published online: 17 July 2026; doi:10.1038/d41591-026-00037-z
The AI agent Biomni performs research tasks across diverse biomedical fields; with further training and optimization, it could be a powerful research partner for scientists.
Who can access testosterone hormone medication in the U.S.?
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Opinion: MAHA is rewriting the vocabulary of American mental health care
At a May MAHA Institute summit organized around the theme of “overmedicalization,” the health secretary announced an action plan to promote psychiatric deprescribing. At first look, it seemed innocuous. The Substance Abuse and Mental Health Services Administration (SAMHSA) would study prescribing trends and publish fact sheets. Medicare would clarify how clinicians can be paid for the attentive work of tapering a patient off of a medication (which is already a part of routine clinical care). Webinars would teach prevention and “holistic” care. A technical expert panel would convene over the summer to make further recommendations.
In reality, this announcement, and the steady stream of actions over the past 18 months, mark a quiet rewriting of the vocabulary of American mental health care — a massive rhetorical shift enacted while programs and protections that would actually solve the problem are dismantled.
STAT+: MDCalc is scoring the clinical calculators used by millions of doctors
Every day, doctors turn to specialized calculators to make decisions about their patients’ care. Kidney performance? There’s a calculator for that. Chance of a successful vaginal birth after a previous C-section? There’s a calculator for that.
Medicine has accumulated hundreds of these clinical scores and decision-making tools, and their numbers continue to grow along with the scale of clinical data. But just because a calculator exists doesn’t mean doctors should always trust its output.
“In clinical practice, a lot of the tools that we use, we genuinely have no idea how limited it is in its validation,” said health systems researcher and gastroenterologist Shazia Siddique. That is why MDCalc, the company Siddique joined last year, is launching a quality-rating system to apply to the more than 800 clinical tools and calculators that doctors use through its site.
Author Correction: Integrated community-based HIV and sexual and reproductive health services for youth: a cluster-randomized trial
Nature Medicine, Published online: 16 July 2026; doi:10.1038/s41591-026-04581-6
Author Correction: Integrated community-based HIV and sexual and reproductive health services for youth: a cluster-randomized trial
Author Correction: Evolution of claudin18.2 therapies in gastroesophageal cancers
Nature Medicine, Published online: 16 July 2026; doi:10.1038/s41591-026-04569-2
Author Correction: Evolution of claudin18.2 therapies in gastroesophageal cancers
Mining antigens for a universal malaria vaccine
Nature Medicine, Published online: 16 July 2026; doi:10.1038/d41591-026-00036-0
Using immunopeptidomics, researchers identify conserved Plasmodium T cell antigens, revealing potential for cross-stage, cross-species malaria vaccine development.
A neuroprosthesis for restoring hand movement and sensation in a person with complete tetraplegia
Nature Medicine, Published online: 16 July 2026; doi:10.1038/s41591-026-04498-0
A bidirectional sensorimotor neuroprosthetic system that decodes brain signals associated with movement intention while delivering patterned neuromodulation to the spinal cord and cortex provides long-term recovery of hand motor and sensory function, even when the device is off.