Background/Objectives: Suboptimal dietary patterns are among the leading modifiable contributors to global morbidity and mortality, particularly in cardiovascular disease, type 2 diabetes mellitus (T2DM), obesity, metabolic syndrome, and hypertension. Digital nutrition platforms have emerged to improve adherence to evidence-based dietary strategies; however, many systems lack structured optimization, processing-aware nutrient profiling, and explainable artificial intelligence (AI) mechanisms. The integration of large language models (LLMs) into digital health introduces conversational personalization but also risks hallucination and unsafe outputs without constraint enforcement. This study aimed to describe the system development, architecture, database infrastructure, optimization algorithms, explainability enforcement, and digital health implications of NutriSteppe-AI, a chatbot-first LLM-driven system for personalized health menu generation constrained by deterministic nutrient logic and processing-aware scoring. Methods: NutriSteppe-AI integrates: (1) a multi-source structured nutrient database of 20,000 food products with up to 130 tracked nutrients; (2) energy requirement estimation using the revised Harris-Benedict equation; (3) linear programming-based multi-objective optimization; (4) a Healthy Food Index (HFI; 0.5-5.0 scale) incorporating NOVA processing classification penalties; (5) traffic-light nutrient gating; and (6) a constrained LLM orchestration layer governed by structured API contracts. Algorithmic validation was performed using 10,000 simulated user profiles spanning diverse age, anthropometric, activity, dietary exclusion, and budget parameters. Results: The system achieved 96.8% full constraint satisfaction with macronutrient mean absolute errors of 11.60% (energy), 18.86% (protein), 16.26% (fat), and 20.91% (carbohydrates). Incorporating NOVA processing penalties reduced ultra-processed food HFI scores by 0.73 points (p < 0.001). Median optimized menu HFI improved from 3.6 to 4.3. Median system latency was 1.8 s. Explainability validation confirmed 100% deterministic alignment with zero hallucinated numeric claims. Conclusions: NutriSteppe-AI demonstrates that LLM-driven nutrition chatbots can achieve deterministic, explainable, and clinically aligned performance when governed by structured optimization, processing-aware scoring, and explainability enforcement. This architecture provides scalable digital health infrastructure for cardiometabolic disease prevention in diverse populations.

The global burden of diabetes mellitus and its chronic complications-including premature atherosclerotic cardiovascular disease and microvascular impairments such as nephropathy, retinopathy, and neuropathy-highlights the need for improved strategies for the early identification of individuals at risk of carbohydrate metabolism disorders. Growing evidence suggests that alterations in the microcirculatory bed occur concomitantly with, or may even precede, the development of cardiovascular disease. The eye, owing to its transparent anatomical structures, provides a unique opportunity for the in vivo assessment of microvascular changes and offers valuable insights into other vascular territories, serving as a potential "window" into cardiometabolic disorders. Recent advances in microcirculation imaging have enabled detailed, non-invasive evaluation of the retinal microvasculature. Techniques such as scanning laser Doppler flowmetry (SLDF), adaptive optics (AO), optical coherence tomography angiography (OCTA), and laser speckle flowgraphy (LSFG) allow for quantitative assessment of the retinal microvascular bed, demonstrating partial correlation with invasive measures of vascular function and sensitivity to therapeutic interventions. The integration of these imaging modalities into clinical and research settings may facilitate the early detection of microvascular dysfunction, improve risk stratification, and support the monitoring of disease progression and treatment efficacy in patients with carbohydrate metabolism disorders. Therefore, this review aims to summarize the current evidence on retinal microvascular alterations in carbohydrate metabolism disorders assessed using advanced imaging techniques, focusing primarily on early, subclinical retinal changes that precede the onset of diabetic retinopathy.

Gestational diabetes mellitus (GDM) is an increasingly prevalent metabolic disorder of pregnancy, driven by rising maternal age, obesity, and complex metabolic-inflammatory interactions. Emerging evidence implicates the maternal microbiome as a key modulator of metabolic adaptation during gestation; however, its precise role in GDM pathogenesis remains incompletely defined. This narrative review synthesizes current knowledge on microbiome alterations across gut, vaginal, and oral niches, focusing on their contribution to insulin resistance, metabolic endotoxemia, and immune dysregulation. GDM is consistently associated with reduced microbial diversity, depletion of beneficial taxa (e.g., Akkermansia, Bifidobacterium, Faecalibacterium), and expansion of pro-inflammatory pathobionts, which collectively may impair intestinal barrier integrity and promote low-grade systemic inflammation. These mechanisms are linked to altered insulin signaling and adverse maternal-fetal outcomes. In parallel, microbiome-derived metabolites and early taxonomic signatures have been proposed as potential biomarkers for first-trimester risk stratification, offering an opportunity to overcome the limitations of late diagnostic approaches such as the oral glucose tolerance test. Despite these advances, most available evidence remains associative, with substantial heterogeneity across studies and limited mechanistic validation. The clinical utility of microbiome-based interventions-including dietary modulation, prebiotics, and probiotics-remains promising but inconclusive, with outcomes highly dependent on individual, microbial, and methodological factors. Overall, the maternal microbiome represents a compelling but still evolving target in GDM research. Future progress will depend on standardized methodologies, longitudinal multi-omics studies, and the development of precision medicine approaches capable of integrating microbial, metabolic, and host data. Such advances may enable earlier diagnosis, targeted prevention, and ultimately the disruption of intergenerational metabolic risk.

Background/Objectives: Atrial fibrillation (AF) and chronic kidney disease (CKD) frequently coexist and are associated with a high risk of cardiovascular complications. Previous studies have primarily focused on differences in clinical profiles by anticoagulant therapy or arrhythmia. Only a limited number of studies have evaluated the impact of CKD severity on patients' clinical characteristics. Methods: This retrospective observational study aimed to characterize the clinical profile of contemporary patients with AF and CKD with an estimated glomerular filtration rate (eGFR) of 15-49 mL/min/1.73 m². The analysis included patients with AF from the CRAFT registry (NCT02987062). Patients were divided into two groups according to eGFR: 15-49 mL/min/1.73 m² and ≥50 mL/min/1.73 m². The groups were compared with respect to demographic characteristics, comorbidities, and treatment patterns. Statistical analyses included the Mann-Whitney U test, the chi-square test and multivariable logistic regression analysis. Results: A total of 3203 patients with AF were included, of whom 1153 had eGFR < 50 mL/min/1.73 m². Compared with patients with eGFR ≥ 50 mL/min/1.73 m², those with lower eGFR were significantly older, more often female, and had a higher burden of comorbidities, including arterial hypertension, heart failure, coronary artery disease, and diabetes mellitus. Direct oral anticoagulants were the predominant anticoagulant therapy, irrespective of renal function. Conclusions: Patients with AF and moderate-to-severe CKD present a distinct clinical profile characterized by advanced age and a higher burden of comorbidities. These findings improve the understanding of the clinical profile of patients with AF and moderate-to-severe CKD and may support risk assessment and clinical decision-making.

Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy and is associated with an increased risk of short-term adverse maternal and neonatal outcomes, as well as long-term metabolic disorders in both mothers and offspring. Exacerbated insulin resistance and inadequate compensatory pancreatic β-cell function constitute the core pathophysiological basis of GDM. Adiponectin is an insulin-sensitizing adipokine that plays important roles in glucose and lipid metabolism, inflammatory regulation, and energy homoeostasis. Changes in maternal circulating adiponectin levels during pregnancy are closely associated with reduced insulin sensitivity and increased risk of GDM. This review systematically summarizes the roles of adiponectin and its distinct isoforms, particularly high-molecular-weight adiponectin, in GDM development, metabolic regulation, and early risk assessment. We also integrate potential interactions between adiponectin and placental hormones, nutrient transport, local inflammation, oxidative stress, and exosome-related mechanisms. In addition, this review discusses the key issues related to adiponectin measurement standardization, gestational timing of blood sampling, population heterogeneity, combined prediction models, and their integration into the oral glucose tolerance test (OGTT). The current findings support adiponectin as a candidate biomarker for early GDM risk stratification and combined prediction models; however, adiponectin cannot replace OGTT as a diagnostic criterion.

Background: The onset of type 2 diabetes mellitus (T2DM) is often preceded by prediabetes, a reversible state of insulin resistance and impaired glucose regulation driven by the chronic consumption of a high-calorie diet and sedentary lifestyle. Prediabetes is characterised by impaired glucose tolerance and elevated glycated haemoglobin (HbA1c). Although metformin improves insulin sensitivity, adherence limitations to lifestyle interventions highlight the need for alternative drugs that can be effective even without dietary intervention. In our laboratory, we synthesised a novel ruthenium complex that exhibits elevated biological activity. Accordingly, this study investigated the metabolic effects of a novel ruthenium (II)-uracil Schiff base complex in HFHC diet-induced prediabetic rats, with and without dietary intervention. Methods: Forty-eight male Sprague-Dawley rats (150-180 g) were divided into two groups, the standard diet (n = 12) and HFHC diet groups (n = 36), for prediabetic induction. Prediabetic animals were randomly assigned to respective treatment groups. The ruthenium complex was administered to prediabetic rats once a day, every third day, for 12 weeks, while monitoring changes in blood glucose, caloric intake, and body weight. Results: Diet-induced prediabetes resulted in increased fasting blood glucose and elevated HbA1c. The administration of the ruthenium (II)-uracil Schiff base complex reduced fasting blood glucose, improved insulin levels and ghrelin, enhanced GLUT4 expression, and significantly increased skeletal muscle glycogen, especially when combined with dietary intervention. Conclusions: The findings showed that the ruthenium complex exerts a pronounced effect on ameliorating glucose homeostasis, enhancing skeletal muscle glucose uptake, and improving overall metabolic function.

The vallecula is a mucosal recess of the hypopharynx situated between the base of the tongue and the lingual surface of the epiglottis and bordered laterally by the glossoepiglottic folds. Lesions in this region are uncommon and encompass a broad differential diagnosis, including vallecular cysts, lingual tonsil hypertrophy, minor salivary gland tumors, squamous cell carcinoma, and, rarely, lymphoproliferative disease. Primary extranodal non-Hodgkin lymphoma of the vallecula is exceptionally rare, and follicular large B-cell lymphoma (FLBCL) has not previously been reported at this site. We present the case of a 62-year-old man who presented with progressive dysphagia and persistent globus sensation for 2-3 months. Flexible laryngoscopy demonstrated a well-circumscribed, smooth, cystic-appearing, pedunculated vallecular mass without mucosal ulceration or airway compromise. The patient underwent direct microlaryngoscopy with transoral excisional biopsy. Histopathologic evaluation revealed a high-grade lymphoid neoplasm. Immunophenotyping demonstrated positivity for cluster of differentiation 20 (CD20), cluster of differentiation 10 (CD10), and B-cell lymphoma 6 (BCL6), with co-expression of B-cell lymphoma 2 (BCL2), an elevated Ki-67 proliferation index, and light-chain restriction. Fluorescence in situ hybridization excluded common rearrangements, supporting a diagnosis of CD10-positive LBCL of follicular germinal center origin, classified as FLBCL according to the World Health Organization 5th edition classification of tumors. The patient was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), followed by involved-site radiotherapy (30 Gy), and achieved a complete metabolic response on surveillance positron emission tomography at six months. The literature on lymphoma involving the vallecula and tongue base is limited to small series and isolated case reports. Diffuse LBCL (DLBCL) predominates, whereas other histologic subtypes have been reported only sporadically. Presentations are typically characterized by dysphagia and globus sensation, and definitive diagnosis requires adequate tissue sampling. To our knowledge, this case represents the first reported occurrence of FLBCL arising in the vallecula. Lymphoma should be considered in the differential diagnosis of atypical or persistent vallecular masses, and adequate submucosal tissue sampling is essential for establishing the diagnosis, particularly in lesions with benign-appearing features.

Pyoderma gangrenosum (PG) is a rare, sterile neutrophilic dermatosis characterized by rapidly progressive, painful cutaneous ulcerations and frequently associated with systemic diseases, including inflammatory bowel disease, rheumatologic disorders, and hematologic malignancies. In particular, recognition of PG as a cutaneous manifestation of an underlying hematologic neoplasm can be critical for timely diagnosis of the systemic disease. Postoperative PG after total hip arthroplasty may closely mimic early periprosthetic joint infection and can lead to unnecessary surgical revisions and prolonged antibiotic therapy.  An 83-year-old woman underwent elective right total hip arthroplasty for end-stage osteoarthritis. Her history included arterial hypertension and mild leukocytopenia; the left hip arthroplasty 10 years earlier had been uncomplicated. The index procedure and early postoperative course were initially uneventful. On postoperative day 6, erythema developed around the wound, followed by pustule formation, purulent-hemorrhagic secretion, and a secondary rise in C-reactive protein (CRP). Early periprosthetic joint infection was suspected, and the patient underwent two revision surgeries with extensive debridement, head and liner exchange, and broad-spectrum antibiotics. Intraoperatively, inflammation remained confined to skin and subcutaneous tissue without fascial or muscular involvement, and microbiological cultures were largely negative or yielded organisms interpreted as contaminants. Dermatologic consultation and histopathologic examination ultimately confirmed PG. Negative-pressure wound therapy was discontinued, topical wound management was continued, and systemic corticosteroids were initiated after early granulation tissue formation, resulting in gradual local improvement and secondary wound healing. Given the known association between PG and hematologic malignancies, a targeted hematologic work-up was performed and subsequently revealed an underlying hairy cell leukemia, providing a unifying explanation for the patient's chronic leukocytopenia. Postoperative PG after elective total hip arthroplasty is a diagnostic challenge that may be misinterpreted as early periprosthetic joint infection. Atypical wound deterioration with severe pain, superficial distribution of inflammation, negative cultures, and pathergy after surgical interventions should raise suspicion of PG and prompt dermatologic and histopathologic evaluation. In addition, clinicians should be aware of the strong association between PG and hematologic malignancies and pursue appropriate hematologic assessment when clinically indicated. Early recognition and timely immunosuppressive treatment are crucial to avoid repeated surgical trauma and to facilitate prompt identification and management of associated systemic diseases such as hairy cell leukemia.

Primary colonic lymphoma is a rare neoplasm. Perforation with fecal peritonitis as the initial manifestation is an exceptional and life-threatening complication requiring emergency surgical management. We report a case of diffuse large B-cell lymphoma of the colon presenting with fecal peritonitis, highlighting the diagnostic challenges and multidisciplinary approach required. A 70-year-old female patient with a history of hypertension presented to the emergency department with an acute abdomen, septic shock, and generalized peritonitis. Abdominal computed tomography (CT) revealed fecal peritonitis secondary to perforation of a cecal tumor. Emergency right oncologic colectomy with double stoma was performed because of generalized purulent peritoneal contamination. Histopathological and immunohistochemical examination confirmed diffuse large B-cell lymphoma, germinal center type, with a high proliferation index (antigen Ki-67, 90%), cluster of differentiation 79a (CD79a)-positive, and cluster of differentiation 3 (CD3)-negative. The postoperative course was uneventful after a two-day intensive care unit (ICU) stay. The patient received four cycles of immunochemotherapy based on rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). At six months, PET-CT evaluation demonstrated a partial response, and treatment is ongoing to complete six cycles. This case illustrates that colonic lymphoma should be considered in the differential diagnosis of acute abdomen with tumor perforation. Emergency colectomy serves both diagnostic and therapeutic purposes by controlling the septic source and providing tissue for definitive histological diagnosis. Multidisciplinary management combining emergency surgery and adjuvant immunochemotherapy is essential for optimizing outcomes in this rare presentation.

Low-grade appendiceal mucinous neoplasms (LAMN) are rare clinical entities. These lesions are characterized by an expansive growth pattern and a significant propensity for peritoneal dissemination, potentially leading to pseudomyxoma peritonei. Preoperative diagnosis of appendiceal mucinous neoplasm remains a formidable challenge, particularly in female patients, as clinical presentations often mimic common gynecological pathologies. This report describes the case of a 63-year-old female with a history of schizophrenia and previous pelvic surgeries who presented with generalized colicky abdominal pain, vomiting, and diarrhea. Initial diagnostic workup, including computed tomography, suggested a massive pyo/hydrometra and severe pelvic inflammatory disease, for which she received intravenous antibiotic therapy. Despite treatment, persistent pain led to a follow-up imaging study revealing a significant pelvic collection. During exploratory laparotomy, free mucin was identified in the right iliac fossa, and intraoperative biopsy reported acellular mucinous implants. A right hemicolectomy with a terminal ileostomy was performed after identifying a perforated appendix with a tumor base exceeding two centimeters. Histopathological analysis confirmed a low-grade appendiceal mucinous neoplasm, staged as pTis N0 pM1a (Stage IVA), with 16 negative lymph nodes and clear surgical margins. This case illustrates the diagnostic complexity of LAMN in elderly women, where mucinous collections can accurately simulate intrauterine or pelvic inflammatory processes such as massive pyo/hydrometra. It highlights the necessity of including appendiceal neoplasms in the differential diagnosis of complex pelvic masses to avoid iatrogenic rupture and optimize surgical outcomes. Precise surgical technique and long-term oncological surveillance remain critical, as the risk of late recurrence and progression to pseudomyxoma peritonei persists even in cases with acellular mucin and negative margins.