Aldo Ferreira-Hermosillo

Purpose: Although cabergoline is the treatment of choice for prolactinomas, a non‐negligible proportion of patients show incomplete biochemical and/or tumoral response. Although several baseline factors have been associated with dopamine agonist resistance, their predictive value remains inconsistent. We aimed to evaluate whether baseline clinical, biochemical, and gross tumor burden variables are associated with incomplete biochemical and radiological response to cabergoline in prolactinomas using a predefined composite operational outcome. Methods: We conducted a retrospective observational cohort study at a tertiary care center in Mexico City. Adult patients with prolactinomas treated with cabergoline were included. The primary outcome was incomplete response to cabergoline, defined using a predefined operational composite endpoint requiring both prolactin normalization and at least 30% estimated tumor volume reduction during follow‐up. Follow‐up duration and cabergoline dose exposure were summarized descriptively and component analyses evaluated biochemical and radiological response separately. A sensitivity analysis used at least 30% tumor diameter reduction instead of volume reduction. Baseline characteristics were compared between responders and patients with incomplete response. Multivariable models including only baseline variables were constructed to identify independent baseline factors associated with incomplete response. Because maximal tolerated cabergoline dose and the reasons for dose non‐escalation were not uniformly available, this endpoint was used exclusively as a research classification; non‐attainment was not interpreted as clinical treatment failure or dopamine‐agonist resistance. Results: A total of 226 patients were included. Using the primary volume‐based definition, 140 patients (61.9%) were classified as responders and 86 (38.1%) as having incomplete response. Follow‐up duration from cabergoline initiation to the last clinical assessment was calculable in 225 patients, with a median duration of 107 months (IQR 56.5−153.5). The median cabergoline dose at 12 months was 1.5 mg/week (IQR 1.0−2.0), and 61 patients (27.0%) had received ≥ 2 mg/week at that time. In unadjusted analyses, age, sex, baseline estimated tumor volume, and tumor size category were not associated with incomplete response, whereas baseline prolactin showed only a weak non‐significant trend. In the primary multivariable model, none of the baseline variables independently identified patients with incomplete response. In exploratory component analyses, 140 patients (61.9%) achieved both prolactin normalization and ≥ 30% estimated tumor volume reduction, 14 (6.2%) achieved prolactin normalization only, 46 (20.4%) achieved ≥ 30% estimated tumor volume reduction only, and 26 (11.5%) achieved neither endpoint. Higher baseline prolactin was associated with incomplete biochemical response (adjusted OR 1.90 per log10 increase, 95% CI 1.11−3.25; p = 0.019; AUC 0.624), but no baseline variable was independently associated with incomplete radiological response. Conclusion: Using a composite operational definition of incomplete response to cabergoline, no routinely available baseline clinical, biochemical, or gross tumor burden variable was independently associated with the composite endpoint or with incomplete radiological response. Baseline prolactin was associated only with incomplete biochemical response, and discrimination remained limited. Conventional baseline variables appear insufficient for clinically useful prediction, highlighting the need for more comprehensive models incorporating dynamic treatment‐related, imaging features of tumor invasiveness, and molecular markers.

Obesity is a chronic inflammatory disease associated with an increased risk of various medical complications, including cardiovascular problems, diabetes, and infectious diseases. A central element of the immune system associated with inflammation and antimicrobial function is neutrophils. Recently, distinct neutrophil subpopulations have been described in different conditions. One neutrophil subpopulation, the low-density neutrophils (LDN), is of particular interest because LDN numbers increase significantly in several diseases. However, in the context of obesity, there is little information on the appearance and functions of LDN. Therefore, to evaluate whether LDN numbers increase in individuals with obesity and to explore their functional properties, LDN from individuals with normal weight and from individuals with obesity were isolated, and their phenotypes and microbicidal functions were assessed. In individuals with normal weight, LDN showed enhanced respiratory burst and more efficient antibody-mediated phagocytosis than neutrophils. In individuals with obesity, LDN numbers were elevated. However, in these LDN, phagocytosis and NETosis were impaired. Also, LDN from individuals with obesity had lower expression of the phagocytic receptor FcγRIIa. In addition, although LDN from cancer patients have been reported to be immunosuppressive, LDN either from individuals with normal weight or from individuals with obesity did not inhibit the proliferation of T-cells. Together, these findings suggest that obesity induces elevated numbers of LDN. But, these LDN perform phagocytosis and NETosis less efficiently than LDN from individuals with normal weight. This deficiency could explain, in part, the increased disease severity of infections observed in individuals with obesity.

Background/Objectives: Accurate assessment of glycemic control in patients with diabetes and chronic kidney disease (CKD) is challenging because alterations associated with CKD affect the performance of conventional glycemic biomarkers, such as glycated hemoglobin (HbA1c), glycated albumin (GA), and fructosamine, while continuous glucose monitoring (CGM) offers a more comprehensive assessment of glycemic exposure; however, a quantitative synthesis of the correlation between these biomarkers and CGM-derived metrics across CKD stages is lacking. To systematically evaluate the correlation between HbA1c, GA, and fructosamine and CGM-derived glycemic metrics in adults with diabetes and CKD, using CGM as the reference standard. Methods: A systematic review with correlation meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, including studies published between January 2016 and March 2025, indexed in PubMed, Scopus, and Web of Science. Correlation coefficients were transformed using Fisher’s z transformation and pooled using a random-effects model; heterogeneity was assessed using the I² statistic. Results: Ten studies met the eligibility criteria; six provided sufficient data for meta-analysis. The pooled correlation was moderate (r = 0.66; 95% confidence interval [CI]: 0.56–0.74) with substantial heterogeneity (I² = 58.9%). In exploratory biomarker-specific subgroup analyses, GA showed the numerically highest correlation with CGM-derived metrics (r = 0.74; 95% CI: 0.65–0.81), followed by HbA1c (r = 0.65; 95% CI: 0.51–0.75); fructosamine was more variable. Conclusions: No single biomarker demonstrated consistent superiority across CKD stages and treatment modalities. These correlation analyses measure linear association, not clinical interchangeability. Biomarker selection should be individualized according to CKD stage, dialysis status, and CGM availability.

Obesity is a disease associated with an increased risk of various medical complications, including cardiovascular problems, diabetes, and infectious diseases. The higher incidence of infections in individuals with obesity is likely due to impaired immune functions. Neutrophils deploy microbicidal functions. However, it is unclear whether neutrophils in individuals with obesity function effectively against infections. To evaluate whether neutrophils in obesity have dysfunctional antimicrobial functions, neutrophils from individuals with normal weight and from individuals with obesity were isolated, and their phenotype and microbicidal functions were assessed. Neutrophils from individuals with obesity had higher expression of CD66b, CD11b, CD15, CD14, CD18, and CD182 on their membranes. The higher expression of these molecules correlated with higher body mass index, suggesting that obesity is associated with neutrophil activation. Accordingly, the phorbol 12-myristate 13-acetate (PMA)-induced respiratory burst in neutrophils from individuals with obesity was greater than in those from individuals without obesity, whereas phagocytosis and PMA-induced NETosis were comparable between neutrophils from individuals with or without obesity, implying that neutrophil functions are not impaired by obesity. However, neutrophil extracellular trap formation of neutrophils from individuals with obesity was selectively reduced in response to Staphylococcus aureus. Nevertheless, the actual killing of these bacteria was similar between neutrophils from individuals with or without obesity. In contrast, neutrophils from individuals with obesity exhibited impaired killing of Pseudomonas aeruginosa and of Klebsiella quasipneumoniae. Together, these findings suggest obesity induces neutrophil activation but disrupts pathogen-specific antimicrobial mechanisms of neutrophils. This deficiency in pathogen clearance could explain the increased susceptibility to infections observed in individuals with obesity.

Excessive gestational weight gain (EGWG) promotes adverse physiological and molecular changes in the placenta. In the present study, we examined the whole placental transcriptomic profile in women with EGWG to elucidate the molecular basis of EGWG pathogenesis. Whole transcriptome profile was analyzed in placentas from term patients with EGWG compared to controls using RNA-seq. Eight genes were found to be downregulated, and 318 genes were found to be upregulated in the placentas of the EGWG group in comparison with those of the women with adequate gestational weight gain (AGWG). Analysis of differentially expressed genes showed eight biological processes, nine cellular components, and ten molecular functions activated, and ten biological processes, ten cellular components, and ten molecular functions suppressed in the placentas from women with EGWG compared to AGWG. EGWG is characterized by significant alterations in placental gene expression, impacting various biological processes, cellular components, and molecular functions, including activation of chromatin organization and remodeling, nucleoplasm, and histone-modifying activity, and suppression of response to stimulus, organelle, and protein binding.

Introduction: Maturity Onset Diabetes of the Young (MODY) remains an underdiagnosed condition with remarkable genetic variability across populations. While diagnostic tools are based on Caucasian cohorts, Whole Exome Sequencing (WES) studies are needed to identify new genes in non-Caucasians, as up to 77% of patients do not harbor variants of significance in MODY-known genes. No WES studies have addressed the genomic landscape of MODY beyond its canonical genes in Latino populations. We aimed to characterize the genomic landscape of MODY through WES in a Mexican cohort, comparing cases with type 2 diabetes mellitus (T2DM) patients and healthy controls (HC). Methods: WES was performed in 17 patients with MODY, 17 with T2DM and 17 HC. We compared the single nucleotide variant landscape across groups in MODY-known genes and searched for genetic variants with differential enrichment across groups. Results: MODY genes used for routine diagnosis showed low discrimination utility, as patients with MODY, T2DM and HC harbored genetic variants in MODY-known genes at similar frequencies in most cases. We found 14 genes with variants capable of distinguishing MODY from T2DM and HC. Variants in genes such as MAP2K3 , SYT15 , KCNJ12 , PEX5 , and TPTE were found in 75-100% of MODY cases while absent in T2DM and HC. Enrichment analysis revealed involvement in synaptic vesicle trafficking, insulin/IGF pathway-mitogen activated protein kinase kinase/MAPK, and insulin/IGF pathway-protein kinase B/AKT signaling. Discussion: MODY presents a complex genetic architecture in the Mexican population. Besides improving our understanding of glycemic regulation pathways, identified genes may serve as diagnostic biomarkers.

Background/Objectives: This cross-sectional study aimed to validate the Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) against bioelectrical impedance analysis (BIA) in 204 adults. Methods: We evaluated CUN-BAE and body mass index (BMI) as continuous predictors of body fat percentage, total fat mass, and visceral fat. Results: BMI showed stronger correlations with visceral fat (r = 0.941 vs. 0.850) and total fat mass (r = 0.968 vs. 0.828),while CUN-BAE showed a slightly stronger correlation with body fat percentage (r = 0.918 vs. 0.884), the parameter it was designed to estimate. CUN-BAE displayed only a weak correlation with muscle mass (r = 0.153), supporting its specificity for adiposity assessment, whereas BMI showed a moderate correlation with muscle mass (r = 0.551), reflecting its weight-dependent nature. Conclusions: Overall, BMI remains a practical marker of absolute fat mass and visceral adiposity, while CUN-BAE may provide a more refined estimate of relative body fat percentage. Tool selection should be guided by the clinical objective and interpreted as complementary rather than competing measures.

Background: Premature ovarian insufficiency (POI) is a major long-term adverse effect of cyclophosphamide (CYC) therapy in systemic lupus erythematosus (SLE). Reported prevalence varies due to differences in populations, protocols, and diagnostic criteria. Objective: To estimate the prevalence of POI in women with SLE exposed to CYC and explore sources of heterogeneity. Methods: MEDLINE, Embase, Web of Science, Scopus, and LILACS were searched from inception through October 2024. Twenty-one studies were included in the systematic review; 12 CYC-exposed cohorts contributed to the primary meta-analysis. Two reviewers independently extracted data and assessed study quality using the Joanna Briggs Institute checklist. Results: The pooled prevalence of POI in SLE treated with CYC was 15% (95% CI 7-26%), with substantial heterogeneity (I ² = 85%; Cochran’s Q = 73.98 p 2 = 0.0353). In contrast, prevalence among unselected SLE populations was markedly lower, confirming the potential gonadotoxic effect of CYC. Temporal analysis showed reduced prevalence in studies published after 2005 (9%) compared with pre-2005 (29%), coinciding with adoption of Euro-Lupus low-dose protocols. Meta-regression identified age at exposure as a significant predictor (β = 0.21, 95% CI: 0.04-0.38, p = 0.017). Cumulative CYC dose was not independently associated with prevalence, likely reflecting the widespread adoption of lower-dose regimens after 2005. Methodological sensitivity analyses using logit transformation (20.0%, 95% CI 12.7-30.1) and GLMM (14.5%, 95% CI 7.1-27.2) were added to assess model robustness. Funnel-plot and the Egger’s test indicated no evidence of publication bias (p = 0.91). Conclusions: Women with SLE treated with CYC show a substantial burden of POI, with an estimated prevalence of approximately 15%. These results underscore the need for standardized diagnostic criteria, fertility counseling, and individualized treatment decisions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/ , identifier CRD42025641213.