Aleksandra Sosin

Background: Short stature is a frequent clinical problem with a broad differential diagnosis. Emerging evidence indicates that pathogenic variants in the ACAN gene represent an underrecognized cause of growth failure and are often misclassified as idiopathic short stature. Case presentation: We report two pediatric patients harboring pathogenic ACAN gene variants, both presenting with short stature and distinctive facial dysmorphism. The first patient, a 15-year-old boy, exhibited short stature, advanced bone age, and a characteristic facial gestalt, including ptosis, hypertelorism, down-slanting palpebral fissures, and fleshy auricles, features not previously described in association with aggrecanopathy. Genetic analysis revealed a novel heterozygous frameshift variant, c.5677_5684del (p.Glu1893TrpfsTer8), in exon 12 of the ACAN gene. The second patient, a 5.5-year-old girl, presented with short stature, mild facial dysmorphism (down-slanting palpebral fissures and retracted mandible), and feeding difficulties. Copy number variation analysis identified a heterozygous deletion encompassing exons 15–19 of the ACAN gene. In both patients, the endocrine evaluation was unremarkable, and no chronic systemic disease was identified. The genetic findings were concordant with the clinical phenotype, confirming aggrecanopathy as the underlying cause of growth failure. Conclusions: These cases further delineate the phenotypic spectrum of ACAN-related short stature and underscore the diagnostic value of genetic testing in children with unexplained or idiopathic growth failure. Importantly, we expand the dysmorphological phenotype of aggrecanopathy by describing previously unreported facial features, which may facilitate earlier clinical recognition and diagnosis. The timely identification of pathogenic variants in the ACAN gene may have significant implications for patient management and long-term outcomes.

Background: Short stature is a frequent clinical problem with a broad differential diagnosis. Emerging evidence indicates that pathogenic variants in the ACAN gene represent an underrecognized cause of growth failure and are often misclassified as idiopathic short stature.Case presentation: We report two pediatric patients harboring pathogenic ACAN gene variants, both presenting with short stature and distinctive facial dysmorphism. The first patient, a 15-year-old boy, exhibited short stature, advanced bone age, and a characteristic facial gestalt, including ptosis, hypertelorism, down slanting palpebral fissures, fleshy auricles, features not previously described in association with aggrecanopathy. Genetic analysis revealed a novel heterozygous frameshift variant, c.5677_5684del (p.Glu1893TrpfsTer8), in exon 12 of the ACAN gene. The second patient, a 5.5-year-old girl, presented with short stature, mild facial dysmorphism (down slanting palpebral fissures and retracted mandible), and feeding difficulties. Copy number variation analysis identified a heterozygous deletion encompassing exons 15–19 of the ACAN gene. In both patients, endocrine evaluation was unremarkable, and no chronic systemic disease was identified. The genetic findings were concordant with the clinical phenotype, confirming aggrecanopathy as the underlying cause of growth failure. Conclusion: These cases further delineate the phenotypic spectrum of ACAN -related short stature and underscore the diagnostic value of genetic testing in children with unexplained or idiopathic growth failure. Importantly, we expand the dysmorphological phenotype of aggrecanopathy by describing previously unreported facial features, which may facilitate earlier clinical recognition and diagnosis. Timely identification of pathogenic variants in ACAN gene may have significant implications for patient management and long-term outcomes.

Objectives: Suicide remains a pressing global public health issue, claiming over 700,000 lives annually. Despite decades of research, predictive models for suicide risk have seen limited progress, emphasizing the need for innovative approaches. Artificial intelligence (AI) and machine learning (ML) are increasingly recognized for their potential to enhance early detection, risk assessment, and intervention strategies. The objective of this review is to provide a critical evaluation of the role of AI in the detection and prevention of suicide, with particular emphasis on its current implementations, potential benefits, and inherent limitations. Methods: A literature review was conducted for the period spanning 2020 to 2025. Relevant publications were identified through a systematic search of the PubMed database using the keywords: artificial, intelligence, suicide, and prevention. The search retrieved 271 articles, of which 23 met the predefined inclusion criteria and were incorporated into the final analysis. Key findings: Recent developments highlight how AI technologies can support suicide prevention through social media surveillance, clinical decision-making tools, and real-time crisis response systems. However, these advancements are not without challenges. Significant concerns persist around data privacy, algorithmic bias, transparency, and the erosion of human-centered care. Conclusions: While AI-driven tools offer substantial opportunities for suicide prevention, their integration into mental health care must be approached with caution. Ethical safeguards, clinical oversight, and continued research are essential to ensure these technologies complement—rather than compromise—traditional human care. A balanced, multidisciplinary approach is vital to realize the full potential of AI while maintaining patient trust, safety, and dignity.

Introduction: High-altitude pulmonary edema (HAPE) is a life-threatening, non-cardiogenic form of pulmonary edema that typically occurs within 2-4 days after rapid ascent above 2,500 meters. It is characterized by hypoxia-induced pulmonary hypertension, increased capillary hydrostatic pressure, and defected alveolar-capillary barrier integrity. Current preventive strategies include gradual ascent and acclimatization, while descent and supplemental oxygen remain the mainstays of treatment. Pharmacological options, including phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil and tadalafil, appear as promising agents due to their pulmonary vasodilatory effects mediated via the nitric oxide (NO)–cGMP pathway. Description of the state of knowledge: This review synthesizes findings from clinical trials, case series, and mechanistic studies published in the last three decades to evaluate the efficacy and safety of PDE5 inhibitors in both the prevention and treatment of HAPE. Evidence indicates that sildenafil and tadalafil effectively reduce pulmonary artery pressure, improve oxygenation, and preserve endothelial barrier function under hypoxic conditions. Their prophylactic use significantly lowers HAPE incidence in high-risk individuals, while therapeutic administration has demonstrated clinical improvement in established cases, particularly when nifedipine use is contraindicated. However, results from some high-altitude trials remain inconclusive, and individual responses may vary based on ascent profile and susceptibility. Conclusions: Overall, PDE5 inhibitors represent a viable adjunct in HAPE management. Further large-scale, randomized studies are necessary to clarify their optimal use, dosage, and comparative efficacy alongside existing pharmacologic options.

Introduction and purpose: Functional gastrointestinal disorders (FGIDs), such as infantile colic (IC), are conditions that occur without any identified structural or biochemical abnormalities. It is estimated that nearly 20% of infants under five months of age experience infantile colic, which is characterized by episodes of excessive crying that are difficult to soothe. The condition causes significant emotional and economic impact on families and healthcare systems. This review aims to analyse efficacy of various probiotic strains in managing symptoms of infantile colic. Results: Probiotic strains vary in the effects on treating infantile colic. The most extensively analysed probiotic for IC is Limosilactobacillus reuteri DSM 17938 (formerly named Lactobacillus). However, its effectiveness in formula-fed infants is still questionable. Other strains, including Bifidobacterium animalis subsp. lactis BB-12, Bifidobacterium breve CECT7263, and combinations such as Bifidobacterium longum KABP042 with Pediococcus pentosaceus KABP041 have shown promising results, often outperforming L. reuteri and even pharmacological treatments for example with simethicone. Conclusions: Probiotic therapy offers a safe and promising approach to reducing symptoms of infantile colic, especially in breastfed infants. However, its efficacy is strain-dependent and not universal. Further large-scale, high-quality randomized controlled trials are necessary to establish standardized recommendations and explore long-term outcomes. Personalized probiotic interventions targeting the infant gut microbiota may be included in the future of colic management.

Background: Despite standard levothyroxine (LT4) therapy, many patients with hypothyroidism continue to report persistent symptoms such as fatigue, cognitive impairment, and reduced quality of life. This has prompted growing interest in adjunctive therapies, particularly micronutrients and supplements, which may modulate immune function and thyroid gland metabolism. Aim: To evaluate the clinical impact of vitamin D, selenium, zinc, myo-inositol, and synbiotic supplementation in hypothyroid patients—especially those with autoimmune thyroiditis and subclinical hypothyroidism—by analyzing their effects on thyroid function, antibody titers, and patient-reported outcomes. Materials and methods: A systematic literature search was conducted predominantly in PubMed and related biomedical databases. The review included randomized controlled trials (RCTs), systematic reviews, and relevant observational studies published between 2015 and 2025. Studies were analyzed for their findings on selected micronutrients and their influence on biochemical markers (TSH, FT4, FT3, anti-TPO, anti-Tg), immune modulation, and quality of life parameters. Results: Adjunctive supplementation with micronutrients such as selenium, vitamin D, zinc, myo-inositol, and synbiotics shows potential clinical benefits in hypothyroidism management. These include reductions in thyroid autoantibody levels, improvements in thyroid hormone profiles, and better patient-reported outcomes. Synergistic effects were noted particularly for combined regimens, though results varied by baseline nutrient status and study design. Conclusions: Supplementation with selected micronutrients may provide meaningful support in managing hypothyroidism, particularly in patients with residual symptoms despite LT4 therapy. However, larger multi-center RCTs are needed to confirm efficacy, establish optimal dosing, and identify patient subgroups most likely to benefit.

Introduction and Purpose: Functional hypothalamic amenorrhea (FHA) accounts for a significant proportion of secondary amenorrhea and remains frequently overlooked, particularly in active women. Its clinical overlap with polycystic ovary syndrome (PCOS) complicates accurate diagnosis. In athletes, FHA arises primarily from low energy availability, forming a key component of the Female Athlete Triad. This review aims to summarize current evidence on the pathophysiology, diagnostic challenges, and therapeutic strategies for FHA, with emphasis on implications for women engaged in high levels of physical activity. Methods: A narrative literature review was conducted using the PubMed database, covering publications from 2012 to 2025. Search terms included amenorrhea, functional hypothalamic amenorrhea, polycystic ovary syndrome, and female athlete triad. Thirty-two relevant sources were included. Description of the State of Knowledge: FHA develops due to reduced pulsatile secretion of gonadotropin-releasing hormone (GnRH), resulting in suppressed LH and FSH release and impaired ovulation. Key contributing factors-energy deficit, excessive training, and psychological stress-disrupt neuroendocrine regulation and activate the hypothalamic-pituitary-adrenal axis. Recent studies highlight altered cortisol rhythms and changes in neurokinin B and nesfatin-1 as potential mechanisms. Differentiating FHA from PCOS remains a diagnostic challenge, particularly given the high prevalence of polycystic ovarian morphology in both conditions. Hormonal parameters such as SHBG, testosterone, and the LH:FSH ratio provide useful discrimination. Treatment focuses on restoring energy availability through nutritional rehabilitation and activity modification, supported by psychological interventions when indicated. For fertility restoration, pulsatile GnRH therapy offers a physiological approach, while IVF remains an effective alternative. Emerging options-including kisspeptin and L-carnitine-show promise in modulating neuroendocrine pathways. Conclusion: FHA is a prevalent yet underrecognized condition with substantial reproductive and skeletal consequences. Early identification and multidisciplinary management are essential to improving long-term health outcomes, particularly among physically active women.

Introduction: Cluster Headache (CH) is a rare but highly disabling primary headache disorder characterized by unilateral pain and cranial autonomic symptoms. It causes major personal and societal burden due to its impact on patients’ quality of life. Purpose of the study: The aim of this review is to provide a comprehensive analysis of CH, including its epidemiology, diagnostic criteria, risk factors, pathophysiology, and treatment. Recent advances in neurobiology and targeted therapies are highlighted. Description of the state of knowledge: Recognized as the most severe of the trigeminal autonomic cephalalgias, CH combines intense head pain with autonomic dysfunction and a distinct circadian pattern. Epidemiological studies report variability in prevalence across regions and demographic groups, with evidence of late-onset and pediatric cases contributing to diagnostic delays. Several risk factors have been identified, including smoking, alcohol consumption, and disturbances in circadian rhythms. Genetic studies reveal susceptibility loci associated with neurovascular regulation, inflammation, and circadian pathways, suggesting a complex genetic background. Functional and structural neuroimaging consistently implicate hypothalamic dysfunction, which interacts with trigeminovascular and parasympathetic systems. Standard treatment includes acute therapies such as subcutaneous triptans and high-flow oxygen, as well as preventive strategies with verapamil. Recent advances have introduced CGRP monoclonal antibodies and neuromodulation, providing new options for refractory patients. Conclusion: Advances in understanding the neurobiological basis and risk factors of CH have enabled more precise diagnostic and therapeutic approaches. However, further research is needed to optimize management and reduce disease burden.

Introduction and purpose: Systemic lupus erythematosus is a chronic, multifaceted autoimmune disorder. Throughout its course, it affects multiple organ systems, such as the skin, joints, kidneys, cardiovascular system, and central nervous system, among others. Less frequently observed clinical presentations include gastrointestinal involvement and hepatic symptoms. The objective of this review is to present and familiarise readers with these atypical manifestations, which are mostly not included in the diagnostic criteria for lupus, and which can pose a significant diagnostic challenge. Description of the state of knowledge: Gastrointestinal (GI) and hepatic symptoms among patients with lupus may be related to the disease itself, but can also result from the side effects of treatment, viral infections, or emerge as a consequence of the overlap of two diseases. The gastrointestinal tract may exhibit symptoms of the disease at practically any point along its course, from the oral cavity to the anus. The most common GI manifestations include conditions such as oral ulcers, dysphagia, lupus enteritis, protein-losing enteropathy, intestinal pseudo-obstruction, and pancreatitis. Rare, but clinically significant presentations of lupus involving the liver, which are important due to their chronic health consequences, include autoimmune hepatitis and lupus hepatitis. Conclusions: Patients with systemic lupus erythematosus who present with gastrointestinal or hepatic symptoms require prompt diagnosis, as these conditions, if not properly managed, contribute to increased mortality. It is also possible for these manifestations to appear as the initial signs of SLE. Therefore, familiarity with their characteristics is crucial to avoid delays in diagnosis and in the implementation of appropriate treatment.

Parasitic infections pose a serious health threat worldwide, especially in developing countries, where they affect millions of people. Traditionally, they are seen mainly as something that impacts on the immune system and physiological functions but now more often potential mental health influence is also pointed out. In particular neurotropic parasites, like Toxoplasma gondii, Plasmodium falciparum, Taenia solium i Trypanosoma brucei are capable of modifying brain function which can lead to development of various mental disorders like schizophrenia, depression, epilepsy and sleep disorders. The purpose of this literature review is to analyze the available research on neurobiological mechanisms that show how parasites influence brain function and behaviour. Attention was given to main mechanisms such as changes in neurotransmission, microglial activation, inflammatory responses and structural changes in the brain. In the research results of brain imaging studies (MRI PET) were discussed. They can help understand these mechanisms in detail. Based on literature review, the role of environmental factors and comorbid conditions are also presented. Conclusions indicate the necessity of further research, that will allow understanding of the neurobiological mechanisms of parasitic infections and their influence on mental health.