Background: Coffin-Siris syndrome (CSS) is an uncommon genetic condition that is generally associated with developmental delay, craniofacial dysmorphism, hypertrichosis, and hypoplasia or aplasia of the fifth digit. Genetic variations in genes that encode components of the SWI/SNF chromatin-remodeling complex, such as SMARCA4, are known to cause CSS with variable phenotype expression. The expanded use of genotype-first methods has contributed to the broadening of the awareness of non-classical presentations. Case Description: We present a case of a 10-year-old girl who presented for genetic evaluation because of developmental delay, anxiety with nonverbal behavioral predominance, cleft palate repair, microcephaly, and short stature. At the age of 3 months, she was diagnosed with congenital hypothyroidism and has been on constant levothyroxine. Examination physical examination showed hypertrichosis, mild craniofacial dysmorphism, and benign joint hypermobility, intact fifth digits and nails. A heterozygous variant in SMARCA4 was identified using trio exome sequencing (c.3315G>T) which revealed a de novo heterozygous variant. A variant of uncertain significance (VUS) in AP1S2 was also identified. Past cytogenetic and molecular testing had eliminated other genetic causes of syndromic developmental delay. The multidisciplinary management incorporated surgery revision of cleft palate repair, endocrine treatment, pharmacologic treatment of anxiety, behavioral treatment, and educational assistance. Conclusions: The case presents a SMARCA4-associated phenotype of the CSS with intact fifth digits and with congenital hypothyroidism. This association has not been described in the literature to our knowledge. The findings reinforce the significance of genetic testing in children with complex patterns of development even without the traditional physical manifestations and propose that endocrine features can be considered further in SMARCA4-related CSS.

Introduction: Symptomatic hyperprolactinemia is rarely seen in children, particularly among those with complex neurodevelopmental disorders. While risperidone is known to raise prolactin levels, cases with clear clinical symptoms are uncommon. This report describes an unusual presentation of hyperprolactinemia in a 12-year-old girl with Landau–Kleffner syndrome, autism spectrum disorder, and intellectual disability, whose symptoms closely resembled pituitary pathology. Case presentation: The 12-year-old Hispanic Peruvian female was under long-term behavioral control therapy of risperidone. With time, she got galactorrhea, visual impairments, and falls. Laboratory revealed high serum prolactin (40.2 ng/mL) and normal thyroid and negative beta-hCG level. No pituitary lesion was seen on neuroimaging. Behavioral symptoms increased following the discontinuation of risperidone, after which the substitution of the latter with olanzapine led to complete restoration. Three months later galactorrhea disappeared, vision improved, and prolactin level was restored (2.2 ng/mL). The mother of the patient was relieved to find out that it was a medication-related issue, but not a tumor and indicated a significant enhancement in the overall behavior and quality of life of her child. Conclusions: The case shows the significance of following prolactin levels in children who are on risperidone therapy particularly those who are non-verbal or those who cannot communicate any discomfort. Clinicians are to remember that risperidone leads to hyperprolactinemia which can simulate pituitary malfunctions. Early identification, educating caregivers, and substitution of prolactin-stimulating drugs with prolactin-sparing ones like olanzapine will allow avoiding unnecessary investigations and enhancing the clinical and family outcomes.

Inflammation and malnutrition are important contributors to adverse outcomes in heart failure (HF). The neutrophil percentage-to-albumin ratio (NPAR), derived from routinely available laboratory parameters, integrates inflammatory burden and nutritional status and may provide prognostic value. We conducted a systematic review in accordance with the PRISMA 2020 guidelines to evaluate the association between baseline or admission NPAR and all-cause mortality in adults with HF. Two independent reviewers performed study selection and data extraction, and methodological quality was assessed using the Newcastle–Ottawa Scale. Because of heterogeneity in study populations, NPAR cutoff values, and outcome definitions, meta-analysis was not performed and findings were synthesized narratively. Five observational cohort studies comprising more than 4900 patients were included. Across all studies, elevated NPAR was consistently associated with increased short-term (30–90 days) and long-term (1–5 years) all-cause mortality in diverse HF populations, with reported hazard ratios ranging from 1.52 to 2.18. Several studies also demonstrated superior prognostic performance of NPAR compared with neutrophil percentage or serum albumin alone. However, reported NPAR cutoff values varied and remain unstandardized. Elevated NPAR is consistently associated with increased all-cause mortality in patients with HF and may serve as a simple, cost-effective tool for clinical risk stratification. Prospective studies are needed to establish standardized thresholds and validate its prognostic utility across HF phenotypes and clinical settings.

Background: Treatment-resistant depression (TRD) is an operational category based on inadequate outcome after adequate antidepressant treatment. The same label may encompass insufficient treatment exposure, an incorrect primary diagnosis, clinically important comorbidity, or depressive illnesses with different maintaining mechanisms. This heterogeneity limits the clinical meaning of treatment history alone and complicates individualized care. Objective: To integrate evidence on diagnostic reassessment, suicide risk, neurobiology, psychological and functional factors, and treatment, and to define a clinically testable personalized medicine framework for TRD. Methods: Targeted PubMed/MEDLINE searches were conducted from database inception through 31 July 2026 and supplemented by reference-list searching. Two authors independently assessed publications for relevance, and disagreements were resolved by discussion and consensus. Ninety-six sources were included and synthesized narratively. Results: Inadequate exposure or adherence can produce pseudo-resistance, whereas bipolar spectrum illness, neurodevelopmental or trauma-related conditions, personality pathology, sleep or substance-related disorders, and medical disease may represent alternative diagnoses, comorbidities, or modifiers of treatment course. Glutamatergic signaling, impaired plasticity, stress-system dysregulation, inflammation, circadian disturbance, metabolism, and neural circuitry contribute to heterogeneity at the group level but do not define validated individual subtypes. Established pharmacological, psychological, and neuromodulatory interventions should be selected according to diagnosis, severity, urgency, previous response, comorbidity, functional impairment, safety, feasibility, and patient preference. Conclusions: TRD is an operational treatment-history category, not a unitary disease. A personalized medicine approach begins with confirmation of major depressive disorder, adequate treatment exposure and adherence, followed by parallel treatment of depression and clinically relevant comorbidity. Biomarkers should guide allocation only when they provide prospectively validated predictive value beyond high-quality clinical and functional assessment.

Background: Attention-deficit/hyperactivity disorder (ADHD) has traditionally been understood through executive and frontostriatal models, but increasing evidence suggests that metabolic, inflammatory, circadian, and neuroendocrine mechanisms may also contribute to clinical heterogeneity. The hypothalamus is a central regulatory hub for appetite, sleep–wake organization, stress responsivity, autonomic function, and endocrine signalling. Objective: This review evaluated evidence linking ADHD with hypothalamic inflammation and related metabolic, inflammatory, circadian, and neuroendocrine dysregulation, with particular emphasis on appetite regulation, sleep and circadian function, stress reactivity, and pharmacological treatment response and tolerability. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Embase, PsycINFO, Scopus, and Web of Science Core Collection from database inception to 31 May 2026. Human observational and intervention studies formed the primary evidence base. Evidence was synthesized narratively. Where available, quantitative findings from previously published meta-analyses were summarized to provide an overview of the strength and consistency of the evidence. Results: The reviewed evidence indicates that ADHD is associated with increased obesity risk, altered appetite-related hormones, immune-inflammatory changes, delayed circadian timing, atypical cortisol responsivity, and treatment-related effects on appetite, sleep, cardiovascular physiology, and tolerability. The strongest quantitative evidence concerned obesity, inflammatory markers, appetite hormones, and type 2 diabetes risk. Direct evidence for hypothalamic inflammation in ADHD remains limited, but converging indirect findings support hypothalamic and neuroendocrine mechanisms as biologically plausible contributors in a subgroup of individuals with ADHD. Conclusions: ADHD appears to be associated with broader metabolic, inflammatory, circadian, and neuroendocrine vulnerabilities beyond its core attentional and behavioural symptoms. Hypothalamic pathways should be interpreted as a mechanistic hypothesis rather than an established causal mechanism. Future longitudinal and multimodal studies are needed to clarify causality and identify biologically defined ADHD subgroups.