Gina Gheorghe

Background: The mechanistic link between HERV-associated transcript expression and the inflammatory pathways involved in colorectal cancer (CRC), particularly the IL-17 axis, remains insufficiently characterized. We performed an exploratory paired-tissue study to investigate whether HERV-associated transcript deregulation in CRC aligns with a distinct local inflammatory signature, potentially consistent with endogenous retroviral re-expression linked to local immune activation and viral mimicry-related processes within the tumor microenvironment. Methods: Matched colorectal tumor tissue (T) and histologically tumor-free adjacent tissue (N) were obtained from 21 treatment-naive CRC patients. Expression of selected HERV-associated loci/transcripts (HERV-FRD, HERV-R, HERV-K, HERV-V1, HERV-1, HERV-H, and ERVWE1), HHLA1/HHLA2, IL-17 family members, and NFKB1 was assessed by RT–qPCR. Results: CRC tumors exhibited selective upregulation of HERV-FRD, HERV-R, HERV-K, HERV-V1, ERVWE1, HHLA1, and HHLA2, whereas HERV-1 and HERV-H showed no significant paired differences. IL-17E was also increased in tumor tissue, while NFKB1 did not show significant paired variation. Paired differential expression analysis [Δ(T−N)] identified a coordinated HERV/ERVWE1 signature that positively correlated with IL-17E after FDR correction, whereas HHLA1/HHLA2 displayed partially distinct behavior. No consistent associations were observed with clinicopathological variables. Conclusions: CRC appears to harbor a selective HERV/ERVWE1-associated transcriptional program linked to IL-17E, supporting a candidate inflammatory axis that may reflect a biologically relevant component of the tumor microenvironment. This expression pattern may also be compatible with a localized endogenous retroviral reactivation state linked to viral mimicry-related inflammatory signaling, although this interpretation remains indirect and requires mechanistic validation. These findings are associative and hypothesis-generating, but they provide a conceptual basis for future mechanistic validation and for exploring whether HERV-linked inflammatory signatures may have biomarker or therapeutic relevance in CRC.

Encephalopathy is a heterogeneous clinical syndrome with numerous neurological and systemic etiologies. We report the case of a 67‐year‐old man, a chronic ethanol consumer, admitted with a one‐week history of confusional syndrome. Initial laboratory tests revealed severe hypercalcemia, acute kidney injury, mild anemia, and hyperproteinemia. Serum ammonia levels were within normal limits, reducing the likelihood of hepatic encephalopathy despite the patient's chronic ethanol use. Cerebral imaging excluded acute cerebrovascular events, while abdominal ultrasound demonstrated splenomegaly and normal‐sized kidneys. Serum protein electrophoresis and immunofixation identified a monoclonal IgG‐kappa component, strongly suggestive of multiple myeloma. The patient's neurocognitive symptoms improved rapidly following systemic corticosteroid therapy and fluid–electrolyte rebalancing, confirming hypercalcemia as the primary mechanism of encephalopathy. Hypercalcemic encephalopathy as an initial manifestation of multiple myeloma is exceedingly rare. This case highlights the diagnostic complexity in elderly patients with multiple potential contributors to altered mental status, including chronic ethanol exposure and renal dysfunction. The presence of normal renal dimensions, unexplained hypercalcemia, and a monoclonal component should prompt evaluation for plasma cell malignancy. Early recognition of hypercalcemia‐induced encephalopathy and prompt investigation for underlying hematologic malignancy are essential to prevent irreversible organ damage and to ensure timely initiation of specific therapy.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and is frequently associated with multiple comorbidities. Bioelectrical impedance analysis (BIA) provides additional information on body composition and may contribute to the multidimensional assessment of patients with COPD. This study aimed to explore the relationship between BIA-derived parameters and clinical characteristics in hospitalized patients with COPD. Materials and Methods: A cross-sectional analysis of baseline data from a prospective cohort was conducted. A total of 72 hospitalized patients with COPD were included, according to predefined inclusion and exclusion criteria. All patients underwent multifrequency BIA using the InBody 380 device. Sociodemographic, clinical, and paraclinical data were collected and analyzed in relation to BIA-derived parameters. Results: Among the bioimpedance-derived parameters, phase angle (PhA) showed a significant correlation with clinical indices of disease severity, including the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index and the modified Medical Research Council (mMRC) dyspnea scale. Hydration-related parameters reflecting extracellular fluid distribution were associated with the presence of heart failure as a comorbidity. In addition, the evaluation of body fat using bioimpedance identified a higher number of patients with excess body fat compared with obesity defined according to the classical body mass index–based criteria. Conclusions: BIA may provide clinically relevant information on body composition and fluid distribution in patients with COPD. These findings support the potential role of BIA as a complementary tool in the multidimensional evaluation of multimorbid patients with COPD, although further studies are needed to clarify its prognostic value and clinical applicability.

Background/Objectives: Antimicrobial resistance (AMR) remains a major global health threat, strengthening the case for antimicrobial stewardship strategies that limit unnecessary broad-spectrum empiric therapy while preserving timely escalation when clinically warranted. Before any clinical deployment of large language model (LLM)-based antibiotic decision support can be considered, structured offline evaluation is needed to assess whether model outputs align with auditable stewardship constraints under real-world admission contexts. We therefore evaluated whether post hoc LLM-generated empiric antibiotic recommendations showed greater concordance with a pre-specified stewardship benchmarking framework than clinician-initiated regimens in a retrospective shadow-mode setting. Methods: Single-center retrospective paired evaluation at Clinical Emergency Hospital of Bucharest (Internal Medicine, 2020–2024). The unit of analysis was the admission (N = 493), with paired 24 h empiric regimens (clinician-prescribed vs. post hoc LLM-recommended via OpenAI API; not visible to clinicians; no influence on care). Local laboratory-derived epidemiology was precomputed from microbiology exports and provided as structured prompt context to approximate information parity with clinicians’ implicit local ecology knowledge. Primary (prespecified) endpoint: any contextual guardrail violation (unjustified carbapenem/antipseudomonal/anti-MRSA under prespecified structured severity/MDR-risk rules), exact McNemar. Key secondary (prespecified): Δ contextual guardrail penalty (LLM − Clin), sign test and Wilcoxon signed-rank (ties reported). Ethics committee approval was obtained. Results: Guardrail violations occurred in 17.0% of clinician regimens vs. 4.9% of LLM regimens (paired RD −12.2%; matched OR 0.216, 95% CI 0.127–0.367; McNemar exact p = 1.60 × 10⁻¹⁰). Δ penalty had median 0 with 398/493 ties; among non-ties, improvements (Δ < 0) exceeded adverse shifts (79 vs. 16; sign-test p = 3.47 × 10⁻¹¹). Conclusions: In this offline, non-interventional paired evaluation, LLM-generated empiric regimens showed greater concordance with a pre-specified stewardship benchmarking framework than clinician empiric regimens for the same admissions. These findings should not be interpreted as evidence of clinical superiority, patient safety, or causal effectiveness, but rather as process-level benchmarking within a rule-based stewardship construct. As such, reproducible guardrail-based benchmarking may serve as an early pre-implementation step to identify alignment and potential failure modes before prospective, safety-governed evaluation.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a systemic condition in which muscle wasting, malnutrition, and altered fluid balance strongly influence prognosis. While spirometry remains essential for diagnosis and staging, it often fails to reflect the heterogeneity of outcomes. Multifrequency bioelectrical impedance analysis (MF-BIA) enables the assessment of body composition and fluid distribution, offering additional prognostic information. This systematic review aimed to evaluate the prognostic significance of MF-BIA in COPD, with emphasis on outcomes such as mortality, exacerbations, and hospital admissions. Materials and Methods: We systematically searched PubMed, Web of Science and Scopus from inception to 29 April 2025. The earliest record retrieved was published in 1996 but was excluded during screening. Studies including COPD patients in whom MF-BIA-derived parameters were related to clinical outcomes were eligible. Risk of bias was assessed using the Newcastle–Ottawa Scale. Data on design, population, methodology, and endpoints were extracted and narratively synthesized due to heterogeneity. The review protocol was not registered. Results: Eight studies were included. Phase angle (PhA) consistently showed prognostic value, being inversely related to mortality and rehospitalizations. Fat-free mass index (FFMI) was integrated into multidimensional models, but its independent role was inconsistent. Parameters describing fluid distribution, such as Extracellular Water/Total Body Water ratio, also appeared relevant, though interpretation was often limited by the absence of consistent consideration of underlying cardiac disease. Conclusions: MF-BIA provides useful prognostic insights in COPD patients, particularly through PhA. It may refine risk stratification beyond spirometry, yet further prospective studies with standardized methods are needed to confirm its independent value. Heterogeneity of methods and small sample sizes remain important limitations.

Background/Objectives: MiRNAs have demonstrated promising roles in the diagnosis of pancreatic cancer and in the prognostic assessment of affected patients. Methods: We conducted a prospective pilot study including 23 patients diagnosed with advanced-stage pancreatic cancer and 10 healthy controls, matched by age and sex. In the screening phase, we evaluated the expression of 176 miRNAs in pooled plasma samples from both groups using real-time PCR. Subsequently, we validated the overexpression of selected miRNAs in individual plasma samples using the same technique. Statistical analysis was performed using IBM SPSS Statistics version 29. Results: During the screening phase, 22 miRNAs exhibited differential expression in patients with pancreatic cancer compared to healthy controls. Among these, hsa-miR-100-5p (27.8-fold increase), hsa-miR-122-5p (7.5-fold), hsa-miR-885-5p (7.2-fold), hsa-miR-34a-5p (5.7-fold), and hsa-miR-193a-5p (4.4-fold) showed the most pronounced upregulation. In the validation phase, all five candidates demonstrated significant overexpression in individual plasma samples (p < 0.001). Their circulating levels also showed associations with tumor stage (p < 0.05). Conclusions: Our findings highlight a distinct circulating miRNA signature associated with advanced pancreatic cancer, supporting the potential role of hsa-miR-100-5p, hsa-miR-122-5p, hsa-miR-885-5p, hsa-miR-34a-5p, and hsa-miR-193a-5p as minimally invasive biomarkers for disease detection and staging. Larger, multicenter studies including early-stage patients and disease control groups will be required to validate these biomarkers and determine their clinical utility.

Background/Objectives: Mismatch repair (MMR) deficiency assessment has proven to be a valuable tool for prognostic evaluation and therapeutic management guidance in patients with colorectal cancer (CRC). Our study aimed to investigate the associations between MMR deficiency and a range of clinicopathological parameters. Methods: We conducted a retrospective observational study including 264 patients diagnosed with CRC, for whom immunohistochemical (IHC) data were available. Statistical analysis was performed using the Python 3.12.7 programming language within the Jupyter Notebook environment (Anaconda distribution). Results: MMR deficiency was identified in 18.18% of patients. It was significantly associated with younger age (p < 0.001). MLH1 and PMS2 were the most frequently affected proteins, with concurrent loss in 77.08% of MMR-deficient cases. Loss of MLH1 expression correlated with female sex (p = 0.004), right-sided location (p < 0.001), poor differentiation (p < 0.001), and loss of CDX2 expression (p < 0.001). Additionally, the loss of PMS2 expression was associated with female sex (p = 0.015), right-sided tumor location (p = 0.003), and poor differentiation (p < 0.001). No significant associations were identified between MMR status and tumor stage, histological subtype, PLR, or NLR values. Conclusions: Gaining deeper insights into the clinical relevance of MMR status in CRC could contribute to improved testing rates and support the design of tailored management strategies that address the specific biological features of these tumors.

The gut microbiome, a complex community of microorganisms residing in the intestinal tract, plays a dual role in colorectal cancer (CRC) development, acting both as a contributing risk factor and as a protective element. This review explores the mechanisms by which gut microbiota contribute to CRC, emphasizing inflammation, oxidative stress, immune evasion, and the production of genotoxins and microbial metabolites. Fusobacterium nucleatum, Escherichia coli (pks+), and Bacteroides fragilis promote tumorigenesis by inducing chronic inflammation, generating reactive oxygen species, and producing virulence factors that damage host DNA. These microorganisms can also evade the antitumor immune response by suppressing cytotoxic T cell activity and increasing regulatory T cell populations. Additionally, microbial-derived metabolites such as secondary bile acids and trimethylamine-N-oxide (TMAO) have been linked to carcinogenic processes. Conversely, protective microbiota, including Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii, contribute to intestinal homeostasis by producing short-chain fatty acids (SCFAs) like butyrate, which exhibit anti-inflammatory and anti-carcinogenic properties. These beneficial microbes enhance gut barrier integrity, modulate immune responses, and inhibit tumor cell proliferation. Understanding the dynamic interplay between pathogenic and protective microbiota is essential for developing microbiome-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, to prevent or treat CRC. Future research should focus on identifying microbial biomarkers for early CRC detection and exploring personalized microbiome-targeted therapies. A deeper understanding of host–microbiota interactions may lead to innovative strategies for CRC management and improved patient outcomes.

Background and Objectives: Early-onset colorectal cancer (EO-CRC) has become a significant public health concern due to its alarming rise in incidence and the poor prognosis associated with this disease. The aim of our study was to identify epidemiological, clinical, and paraclinical characteristics that could explain the more aggressive evolution of EO-CRC compared to late-onset colorectal cancer (LO-CRC). Materials and Methods: We conducted a retrospective study over a two-year period, including 204 patients diagnosed with colorectal cancer (CRC). The patients were divided into two subgroups: those with EO-CRC and those with LO-CRC. Statistical analysis was performed using IBM SPSS Statistics, Version 29.0. Results: EO-CRC was identified in 11.3% of the patients included in the study. Compared to LO-CRC patients, EO-CRC patients exhibited a tendency for more distal tumor localization and a stenotic endoscopic appearance (43.5% vs. 29.3%). Regarding histopathological diagnosis, EO-CRC patients demonstrated a higher proportion of the mucinous histologic subtype (34.8% vs. 14.4%) and a significantly greater percentage of poorly differentiated tumors (39.1% vs. 14.5%; p = 0.010). Immunohistochemical results, available for a limited number of patients, revealed higher CDX2 positivity in LO-CRC patients (p = 0.012) and higher HER2 positivity in EO-CRC patients (p = 0.002). Smoking (p = 0.006) and hypertension (p = 0.002) were more prevalent in EO-CRC patients than in LO-CRC patients. Conclusions: Patients with EO-CRC exhibit distinct histopathological and molecular characteristics compared to those with LO-CRC, which may contribute to their poorer prognoses. The higher prevalence of the mucinous histological subtype, poor tumor differentiation, increased HER2 expression, and reduced CDX2 expression suggest potential molecular pathways driving the aggressive nature of EO-CRC. These findings highlight the need for tailored screening strategies and personalized therapeutic approaches in younger CRC patients. Future studies should further investigate the underlying mechanisms and potential biomarkers that could guide early diagnoses and targeted treatments.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is correlated with an increased cardiovascular risk, independent of other traditional risk factors. The mechanisms underlying this pathogenic link are complex yet remain incompletely elucidated. Among these, the most significant are visceral adiposity, low-grade inflammation and oxidative stress, endothelial dysfunction, prothrombotic status, insulin resistance, dyslipidemia and postprandial hyperlipemia, gut dysbiosis, and genetic mutations. Cardiovascular diseases are the leading cause of death in patients with MASLD. These patients have an increased incidence of coronary artery disease, carotid artery disease, structural and functional cardiac abnormalities, and valvulopathies, as well as arrhythmias and cardiac conduction disorders. In this review, we present the latest data on the association between MASLD and cardiovascular risk, focusing on the pathogenic mechanisms that explain the correlation between these two pathologies. Given the high rates of cardiovascular morbidity and mortality among patients with MASLD, we consider it imperative to raise awareness of the risks associated with this condition within the general population. Further research is essential to clarify the mechanisms underlying the increased cardiovascular risk linked to MASLD. This understanding may facilitate the identification of new diagnostic and prognostic biomarkers for these patients, as well as novel therapeutic targets.