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The study of rum evolution is essential to determine the distinctive properties of each variety. The Industria Licorera de Caldas (ILC) promotes research focused on the identification of aging markers in rums and tafias-the latter not produced by the ILC but aged in its oak barrels. These tafias serve as raw material for the production of representative rums such as Ron Viejo de Caldas Tradicional, Ron Viejo de Caldas Juan de la Cruz, Ron Viejo de Caldas Carta de Oro, and Ron Viejo de Caldas Gran Reserva Especial. This research aimed to perform a volatilomic and olfactometric study to characterize and differentiate tafias and rums aged at the ILC from other rum varieties currently available on the market. The olfactometric profile was obtained using headspace solid-phase microextraction (HS-SPME), followed by olfactometry coupled to a gas chromatograph-mass spectrometer (GC-MS-O). The volatilomic profile was determined through liquid injections in GC-MS, while aging markers were exclusively analyzed by liquid injection GC-MS. Aging markers identified included ethyl propanoate, isobutyl acetate, ethyl butyrate, hexanal, butyric acid, ethyl isovalerate, isovaleric acid, ethyl hexanoate, ethyl heptanoate, guaiacol, ethyl octanoate, trans-whiskey lactone, ethyl decanoate, syringaldehyde, eugenol, cis-whiskey lactone, vanillin, and ethyl dodecanoate. These compounds enable differentiation between rums aged by the ILC and those from external producers. The correlation of these compounds with the rum aging process, through volatilomic and olfactometric analyses, highlighted key chemical markers and their olfactory descriptors as differentiating criteria for identifying high-quality rums within the volatile profile characteristic of ILC-produced rums.

To describe the feasibility of Woven EndoBridge (WEB; Terumo Neuro, Aliso Viejo, CA, USA) treatment for an aneurysm at the distal anterior cerebral artery A4 bifurcation and to highlight technical considerations for achieving peripheral access. A 57-year-old woman was incidentally diagnosed with an unruptured distal anterior cerebral artery aneurysm during a brain MRI performed for evaluation of headache. DSA demonstrated a wide-neck aneurysm arising at the A4 bifurcation of a right-dominant bihemispheric distal anterior cerebral artery (neck width, 5.90 mm; dome, 6.53 × 7.76 mm [mean, 7.15 mm]; height, 6.82 mm). Given the broad neck configuration and the necessity of preserving both distal branches, intrasaccular flow disruption using a WEB device was considered appropriate. Advancement through the A1 segment was impeded by steep angulation at the internal carotid artery-A1 junction and a pronounced ledge effect. The buddy-wire technique was initially attempted to improve support and trackability, but was unsuccessful. Stable access to the A2 segment was achieved only after catheter reshaping without further use of the buddy wire. A WEB SL 8 × 3 mm device (Terumo Neuro) was deployed, achieving adequate neck coverage with a marked reduction in aneurysmal inflow while maintaining patency of both distal anterior cerebral artery branches. The procedure was completed without any procedure-related complications. Follow-up MRI/MRA at 1 month showed no evidence of residual aneurysm filling and no branch-related complications. In selected distal anterior cerebral artery aneurysms where branch preservation is essential and parent-artery protrusion can be avoided, WEB treatment may be a useful endovascular option. This case illustrates the feasibility of WEB treatment of aneurysms at the anterior cerebral artery A4 bifurcation.

Protection and management of natural landscapes represent one of the most significant challenges of our time. Indigenous peoples own and manage a large proportion of the world's high biodiversity areas. Studying the landscape by integrating Indigenous knowledge into socioecological systems (SES) analysis requires practical and effective approaches. Here, we present an innovative methodology that characterizes the landscape through the co-production of knowledge between Indigenous and scientific communities. With its graphic language, the methodology maintains technical and cartographic rigour, ensuring the information is easily usable by members of both communities and technical and specialized audiences. We implemented this approach and examined its effectiveness at La Planada Nature Reserve, an area owned and managed by the Awá Pialapí Pueblo Viejo Indigenous Resguardo (Nariño, Colombia). We characterized the landscape and its spaces based on their spatial distribution, structure, temporality, local classification of the landscape and associated cultural aspects. Based on this participatory experience in this reserve, the landscape characterization was used to co-create a nature-based scientific tourism strategy for this protected area. These findings emphasize the value of integrating Indigenous and scientific knowledge to develop a deep understanding of landscape ecology and promote effective conservation strategies.

The CURRENT registry is a prospective, multicenter, real-world investigation designed to evaluate the safety and effectiveness of the Renzan™ stent (Terumo MicroVention Inc., Aliso Viejo, CA, USA) in patients with femoro-popliteal peripheral artery disease (PAD), including complex lesions and chronic limb-threatening ischemia (CLTI). This study reports the interim outcomes at 6 and 12 months. A total of 89 patients with symptomatic PAD (Rutherford category IV-V 64.1%) were enrolled across three centers in Tuscany, Italy. All patients underwent endovascular treatment with the Renzan™ dual-layer interwoven nitinol stent. Baseline and follow-up assessments included clinical evaluation and duplex ultrasound imaging. The primary safety endpoint was the composite rate of all-cause death, target lesion revascularization (TLR), and major amputation at 30 days. The primary efficacy endpoint was primary patency at 6 months. Estimated patency and reintervention rates were reported at 12 months using Kaplan-Meier analysis. Technical and procedural success was achieved in 100% of cases. At 30 days, no deaths, TLRs, or major amputations occurred. At 6 months, the composite safety endpoint was met in 94.3% of patients. Primary patency was 100% at 1 and 3 months, 92.0% at 6 months, and declined to 78.7% (95% CI: 55.3-88.1%) at 12 months. Freedom from TLR was 97.2% at 6 months and 78.5% (95% CI: 63.7-88.7%) at 12 months. Exploratory multivariable analysis identified diabetes mellitus, previous peripheral endovascular intervention, and below-the-knee involvement as independent predictors of loss of patency, whereas dual antiplatelet therapy beyond 1 months was associated with a reduced risk of patency loss. The Renzan™ stent demonstrated excellent early safety and efficacy outcomes in a challenging PAD population, with sustained mid-term patency despite a high proportion of complex lesions. These preliminary results support the use of this new mimetic stent design in real-world clinical settings and warrant further confirmation with longer-term follow-up.

This Woven EndoBridge Database (W-EB DB) study was conducted using data from a nationwide, multicenter database to evaluate the safety and efficacy of the W-EB device (MicroVention, Aliso Viejo, CA, USA; distributed by Terumo, Tokyo, Japan) for the treatment of wide-neck intracranial bifurcation aneurysms in Japanese patients. In this paper, we confirm the clinical usefulness of the W-EB device in Japanese patients based on the comparable 1-year post-procedure outcomes to those reported from overseas. This W-EB DB study was a post-marketing, open-label, non-randomized cohort study conducted using the database of the Japanese Society of Neuroendovascular Therapy (JSNET). A total of 128 participants (including 103 patients with unruptured aneurysms and 25 patients with ruptured aneurysms) treated with the W-EB device between December 2020 and December 2025 at any of the 12 participating centers were included in this study. Clinical data collected from the database consisted of the patient demographics, comorbidities, aneurysm characteristics (location, size, and neck width), procedural details, and follow-up outcomes. The safety endpoints were the incidences of subarachnoid hemorrhage (SAH), rebleeding, cerebral infarction, and other adverse events occurring within 1 year after the procedure. The efficacy endpoints were the aneurysm occlusion rates and retreatment rates at 180 days and 1 year after the procedure; the aneurysm occlusion status was determined in accordance with the W-EB Occlusion Scale (WOS). We used descriptive statistics to analyze the results. The research within our submission was approved by the institutional ethics review board of Kyoto University (Approval No. R2088). In regard to the safety endpoints, SAH occurred in 1 patient (1.0%) with an unruptured aneurysm, and rebleeding occurred in 1 patient (4.0%) with a ruptured aneurysm. The incidence of cerebral infarction was 7.0%. Most other adverse events were mild, and no new device-related risks were identified. In regard to the efficacy of the device, at 1 year post-procedure, complete occlusion (WOS grade A or B) was achieved in 58 of 95 lesions (61.1%) and adequate occlusion (WOS grade A, B, or C) was achieved in 79 of 95 lesions (83.2%). Retreatment was needed for 5 of 126 lesions (4.0%). The safety and efficacy outcomes were comparable to those reported from multicenter studies conducted in Europe and the United States, with slightly higher complete occlusion rates and similar adequate occlusion and retreatment rates. Favorable safety and effectiveness of the W-EB device were observed at 1 year after device deployment in Japanese patients with wide-neck intracranial aneurysms. These findings are consistent with international reports and support the clinical utility of the W-EB device, given the low incidence of serious complications.

This case report describes a rare mechanical etiology of postoperative refractive surprise - anterior displacement of an intraocular lens (IOL) secondary to localized posterior synechiae - in a patient with plateau iris syndrome (PIS) following combined clear lens extraction (CLE) and minimally invasive glaucoma surgery (MIGS). A 29-year-old man with PIS and medically refractory chronic angle-closure glaucoma underwent an uneventful left-eye CLE, goniosynechiolysis, implantation of a toric extended depth-of-focus (EDOF) IOL, and insertion of three iStent infinite® (Glaukos Corporation, Aliso Viejo, CA, USA) devices. Five weeks postoperatively, he presented with blurred vision, asthenopia, and binocular diplopia associated with a sudden -2.50 D myopic surprise. Dynamic slit-lamp examination revealed localized posterior synechiae extending from 1 to 5 o'clock. These adhesions exerted asymmetrical traction on the capsular bag, resulting in anterior displacement and temporal tilt of the IOL complex without pupillary block. The patient subsequently underwent targeted synechiolysis under local anesthesia. Postoperative biometry demonstrated an increase in anterior chamber depth (ACD) from 2.90 mm to 3.02 mm, confirming posterior repositioning of the IOL. Restoration of the effective lens position (ELP) reversed the myopic shift and resolved the patient's symptoms. This case highlights localized posterior synechiae as a rare but reversible cause of postoperative refractive surprise and underscores the importance of meticulous dynamic slit-lamp evaluation and ACD monitoring in patients with complex anterior segment conditions presenting with unexpected refractive outcomes. Timely synechiolysis may serve as a definitive and restorative intervention.

Lurbinectedin in combination with irinotecan showed synergistic antitumor activity in preclinical studies. A phase I/II trial (NCT02611024) evaluated this combination in patients with advanced solid tumors. The phase II stage evaluated the antitumor activity of the recommended dose (RD) (lurbinectedin 2.0 mg/m2 on Day (D)1 plus irinotecan 75 mg/m2 on D1 and D8 q3wk with primary granulocyte colony-stimulating factor prophylaxis) in five tumor-specific cohorts. This pooled analysis describes the safety profile of this combination from 233 patients with different advanced solid tumors treated at the RD. Adverse events (AEs) and laboratory abnormalities were graded using NCI-CTCAE v.4. The most frequent AEs (any grade) related to treatment were fatigue (71% of patients/25% of cycles), diarrhea (62%/17%), nausea (59%/18%), vomiting (35%/7%) and decreased appetite (32%/6%); the most common grade ≥ 3 AEs were fatigue (14%/2%), diarrhea (14%/2%) and febrile neutropenia (9%/1%). The most common grade ≥ 3 laboratory abnormality regardless of relationship was neutropenia (53%). The rate of discontinuation due to treatment-related AEs was 3% (n = 7 patients). There was one treatment-related death (0.4%) involving a 63-year-old male patient (0.4%) diagnosed with metastatic NEN who died due to grade 5 staphylococcal bacteremia. In conclusion, this pooled analysis shows a predictable and manageable safety profile for lurbinectedin in combination with irinotecan in patients with advanced solid tumors, with myelosuppression, fatigue and gastrointestinal disorders being the main toxicities observed.Trial code: ClinicalTrials.gov identifier: NCT02611024.

Leukodystrophies are a clinically and genetically heterogeneous group of diseases characterized by white matter abnormalities on brain magnetic resonance imaging. Clinical, biochemical, molecular, and/or neuroimaging findings collectively support the diagnosis confirmation. The heterogeneous and overlapping clinical presentations of different leukodystrophies and non-diagnostic molecular testing pose a significant challenge to establishing a definitive diagnosis in these rare diseases. The Myelin Disorders Biorepository Project is an observational research program that aims to establish new tests to diagnose leukodystrophies and describe the natural history of these disorders. Ensuring an accurate diagnosis is critical to the goals of this project, and this paper aims to describe the rigorous diagnostic review and confirmation process which was developed. We present a diagnosis review process that contributes to an accurate diagnosis for participants enrolled in this study. Board-certified genetic counselors with expertise in these disorders audit medical records to carefully assess each enrolled participant's clinical, biochemical, and molecular features. A scale of diagnostic categories is assigned based on the record review, and a team of leukodystrophy physician experts consults for cases that require further characterization or clarification. This robust review process has resulted in a database of individuals with verified diagnoses that may be easily queried for inclusion in appropriate natural history studies and/or treatment trials. This is a model framework that may be adapted and implemented by other rare disease groups.

Histotripsy is a non-thermal, non-ionizing focused ultrasound therapy that mechanically disrupts tissue through acoustic cavitation. We present a case of a woman with estrogen receptor-positive metastatic breast cancer who developed progressive multifocal liver metastases despite having failed multiple lines of systemic therapies. She underwent two histotripsy treatments staged approximately six weeks apart, using a lobar approach to sequentially treat left- and right-lobe lesions, targeting a total of 10 hepatic lesions. She tolerated both procedures well without any complications or interruption of her targeted therapy (trastuzumab deruxtecan). Follow-up PET/CT performed two months after the second treatment demonstrated complete metabolic response in the liver and overall disease regression, which was again observed on a subsequent PET/CT performed six months later. Follow-up MR imaging four and seven months after the second histotripsy revealed expected post-treatment involution of the treatment zones. This case highlights the ability of histotripsy to treat patients with advanced liver metastases in a staged fashion to minimize potential toxicities. These encouraging early results support the need for more data to confirm the role of histotripsy in advanced metastatic breast cancer patients who have limited treatment options.

The research model used to conduct the Habitual Diet and Avocado Trial (HAT), a large multicenter clinical trial (n = 1008 participants) designed to evaluate the effect of consuming 1 avocado/d for 6 mo on visceral adiposity in individuals with an increased waist circumference, has been a long-term productive collaboration. The primary outcome analysis showed that intake of 1 avocado/d did not affect visceral adiposity compared with habitual dietary intake. Secondary and ancillary analyses showed improvements in diet quality, LDL cholesterol, and red blood cell fatty acid composition, as well as the gut microbiome with avocado intake. These findings are relevant to a large proportion of the United States population because of the study sample characteristics. The aim of this paper is to summarize the research protocol and implementation of the HAT as well as the findings. This approach could be used by consortia supported by nongovernmental entities. Notably, there is still ongoing research being conducted by the investigators using the data collected from the HAT. Moreover, HAT samples and data are available, pending an approved request, to scientists interested in conducting avocado health research. The collaborative commitment of the investigators, their collegial spirit, along with strong leadership and ongoing support from the coordinating center and funding agency representatives, has created a productive research consortium. This consortium has furthered knowledge about the health effects of avocados, and the approach has maximized the return on the research investment from a single large clinical trial.

Obtaining a precise genetic tuberous sclerosis complex diagnosis is a challenge as many missense TSC2 variants are variants of uncertain significance. Variants of uncertain significance in TSC2 have been resolved by one-at-a-time functional assays, but these assays cannot scale to the 3634 TSC2 missense variants of uncertain significance observed so far. To address this challenge, we use massively parallel sequencing to measure the steady-state abundance of almost 9000 TSC2 missense variants and develop an mTOR pathway activity assay using genome editing and cell sorting to generate activity scores for 391 missense variants. We observe that 1256 of 8864 (14.17%) missense variants assayed have altered TSC2 abundance, and 69 of 391 (17.65%) missense variants assayed have altered mTOR pathway activity. Calibration and integration of these data into classification of variants identified in a clinical cohort putatively reclassifies 212 of 276 (76.8%) TSC2 missense variants of uncertain significance. These datasets will lead to improved genetic diagnosis of tuberous sclerosis complex with potential positive impacts on the clinical management of patients and their families.

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The concept of complexity of care is well established in scientific literature; however, in pediatric populations, research has primarily focused on medical aspects, lacking a comprehensive approach that includes additional influencing factors. This study aimed to identify the evidence on complexity of care among pediatric patients attending pediatric acute care settings. An integrative review was conducted the PRISMA guidelines (PROSPERO registration: CRD42023469426). The search included articles published up to July 2025 in PubMed, CINHAL, Scopus, and WOS. Both the quality and internal validity of the studies included were independently assessed by two reviewers. Twenty-two articles were analysed, identifying 48 complexity-related factors and 39 assessment scales. Findings were grouped into four thematic categories, within each of which the following key complexity factors were identified: A) Clinical aspects of pediatric patients, such as diagnosis, patient type, and clinical stability; B) Environmental factors, particularly family involvement; C) Care provider aspects, such as direct/indirect nursing activities and workload; D) Organisational elements, especially nursing staff experience. This review expands the understanding of complexity beyond patient pathology. It underscores the need for further research to explore healthcare professionals' perceptions of complexity and examine how the identified factors influence health outcomes. Developing integrated assessment tools may enhance care planning and resource allocation in pediatric settings.

Performing germline genetic testing of family members following the identification of an individual with a pathogenic variant in a cancer predisposition gene, a process known as cascade testing, is a critical step in maximizing the preventive benefit of genetic testing for hereditary cancer. To determine how often family members undergo cascade testing and to evaluate demographic, socioeconomic, and clinical factors associated with this process. This retrospective cross-sectional study analyzed demographics, cancer history, genetic test results, and cascade testing data from probands who underwent multigene panel testing between December 2016 and August 2020 at a single diagnostic laboratory. The study cohort included probands found to have a pathogenic or likely pathogenic variant (P/LPV) in Lynch syndrome (MLH1, MSH2, MSH6, PMS2, or EPCAM) or hereditary breast and ovarian cancer (ATM, BRCA1, BRCA2, CHEK2, or PALB2) genes. Statistical analyses were conducted between June 2023 and March 2025. Identification of a P/LPV in a cancer predisposition gene. Variables assessed included proband age, sex, race and ethnicity, socioeconomic status (SES), availability of free testing for family members, cancer history, type of test ordered, and clinician credentials. Differences in cascade testing rates were calculated via 2-sided &#x3c7;2 test. Of 22&#x202f;932 probands (18&#x202f;949 [81.38%] female; mean [SD] age at testing. 51.6 [14.5] years), 5559 (24.24%) had at least 1 family member who underwent cascade testing. Higher rates of cascade testing were seen in individuals aged 40 to 79 years compared with those aged 20 to 39 years (age 40-59 years: 2587 of 10&#x202f;420 probands [24.83%]; P&#x2009;<&#x2009;.001; age 60-79 years: 1960 of 6869 probands [28.53%]; P&#x2009;<&#x2009;.001; age &#x2265;80 years: 129 of 462 probands [27.92%]; P&#x2009;<&#x2009;.001), women (4740 of 18&#x202f;948 female probands [25.02%] vs 817 of 3963 male probands [20.62%]; P&#x2009;<&#x2009;.001), non-Hispanic White individuals (3762 of 13&#x202f;834 probands [27.19%]), those with a personal cancer history vs those without (4712 of 16&#x202f;674 probands [39.43%] vs 847 of 6261 probands [15.64%]; P&#x2009;<&#x2009;.001), and those whose care involved genetic counselors vs those whose did not (3614 of 13&#x202f;847 probands [26.10%] vs 1948 of 9088 probands [21.43%]; P&#x2009;<&#x2009;.001). People with BRCA1 or BRCA2 variants had higher cascade testing rates compared with those with ATM, CHEK2, or PALB2 variants (2614 of 9699 probands [26.95%] vs 2015 of 8973 probands [22.46%]; P&#x2009;<&#x2009;.001). Several disparities were identified, including lower rates of cascade testing among male probands and probands from racial or ethnic minority groups compared with non-Hispanic White probands (227 of 1406 African American or Black probands [16.15%]; P&#x2009;<&#x2009;.001; 175 of 875 Asian probands [20.00%]; P&#x2009;<&#x2009;.001; 319 of 1616 Hispanic probands [19.74%]; P&#x2009;<&#x2009;.001; 17 of 146 Middle Eastern probands [11.64%]; P&#x2009;<&#x2009;.001). SES had minimal associations with testing rates, and free family testing was not associated with boosting participation. In this retrospective cross-sectional study, cascade testing was underused, especially among specific demographic groups, with clinical and cultural factors appearing to play a larger role than financial barriers. These findings may guide efforts to address barriers preventing wider uptake of cascade testing and improve cancer prevention efforts, particularly among racial and ethnic minority groups.

Marine macroalgae remain largely overlooked in global assessments of carbon budgets, despite being dominant and highly productive primary producers in coastal zones. Such assessments require studies at the level of whole assemblages as well as a better understanding of how human-induced shifts affect algal forest metabolism. This study aimed to quantify primary productivity and the carbon balance and stocks of different intertidal macroalgal assemblages in the R&#xed;a de Vigo (Galicia, NW Spain), in order to evaluate how structural shifts from canopy-forming to turf-forming species influence ecosystem functioning. We examined assemblages dominated by large canopy-forming brown algae (Fucus vesiculosus, Ascophyllum nodosum) and by opportunistic and/or turf-forming species. Using incubation chambers in an outdoor mesocosm system, we measured net primary productivity (NPP) and respiration of whole assemblages, quantifying the contribution of macroalgae and of the associated fauna to respiration rates. Estimates of gross primary productivity (GPP), total gross productivity (GP) and net (NP) productivity (i.e. trophic state) were made for each assemblage. Photosynthetic (PQ) and respiration (RQ) quotients were calculated from changes in dissolved inorganic carbon (DIC) and O2, and the values were used to calculate the diel carbon balance. The carbon and nitrogen contents of the dominant macroalgae were also quantified to assess the storage capacity. The study findings show positive diel carbon balances (autotrophic metabolism) during summer in both intertidal fucoid-dominated and turf-dominated assemblages, with a non-significant trend for greater values in the fucoid-dominated site. The observed inverse trends in the diel balances of net O2 fluxes may be linked to low PQ values of fucoid assemblages and higher RQ values of the turf-dominated community. Assemblages dominated by A. nodosum exhibited the highest biomass and specific carbon and nitrogen contents. Projected shifts from large canopy-forming species toward smaller, turf-forming macroalgae maintain a positive carbon balance but are likely to reduce the carbon gains and overall productivity in intertidal habitats.

Circulating microRNAs (miRNAs) may represent promising candidate biomarkers of chronic coronary syndrome (CCS). Nevertheless, their relationship with patterns of coronary dysfunction remains underexplored. This study aims to identify plasma miRNA profiles associated with macrovascular and/or microvascular patterns of coronary dysfunction. Prospective, multicenter cohort study that enrolled consecutive patients with chest pain of presumed coronary origin who were referred for invasive physiological evaluation, which included measurement of fractional flow reserve (FFR) and the index of microcirculatory resistance (IMR). Based on FFR and IMR values, patients were categorized into four groups: normal coronary indices; isolated microvascular dysfunction; isolated macrovascular dysfunction; and combined macrovascular and microvascular dysfunction. miRNA profiling was performed using RT-qPCR. An unsupervised hierarchical clustering approach was applied to identify miRNA-based clusters (miRNotypes). 128 patients were included and were distributed across study groups as follows: 37.5% normal coronary indices, 23.4% isolated microvascular dysfunction, 19.5% isolated macrovascular dysfunction; and 19.5% combined macro- and microvascular dysfunction. Plasma miRNA profiles in patients with isolated macrovascular dysfunction differed significantly from those with normal indices and microvascular dysfunction. miR-21-5p and miR-92a-3p were independently associated with coronary macrovascular dysfunction. Incorporating a 3-miRNA signature (miR-17-5p, miR-21-5p, miR-92a-3p) was associated with improved reclassification metrics when added to a clinical model (IDI&#xa0;=&#xa0;0.082, p-value&#xa0;=&#xa0;0.002; NRI&#xa0;=&#xa0;0.576, p-value<0.001). Unsupervised clustering revealed three distinct plasma miRNotypes associated with specific patterns of coronary dysfunction. In patients with suspected CCS, circulating miRNA profiles differ between patterns of coronary involvement. Plasma miRNA-based molecular phenotyping could potentially complement existing clinical tools aiding in the identification of coronary macrovascular dysfunction.

The Geisinger Inherited Risk Gastrointestinal clinic (IRGI) offers annual multidisciplinary care to patients with Lynch syndrome (LS). Adherence to recommended colonoscopy and esophago-gastro-duodenoscopy (EGD) surveillance among IRGI patients with LS were compared with patients with LS not followed by IRGI (non-IRGI). A validated query of electronic health record data was performed. Gene-specific guidelines were used to determine adherence to recommended surveillance following result disclosure until March 2025. For those who received results before 2016, adherence was assessed from April 2016 to March 2025. Pearson's chi-square, Fisher's exact, Wilcoxon rank-sum tests, and logistic regressions were performed to compare adherence to recommended surveillance between IRGI and non-IRGI patients. A total of 548 patients with LS were included, of which 167 (30.5%) attended IRGI and 381 (69.5%) did not. Patients who were younger (odds ratio [OR], 1.03 [95% CI, 1.01 to 1.04]; P = .0002) or were identified via indication-based testing (OR, 9.69 [95% CI, 5.63 to 17.1], P < .0001) were more likely to be IRGI patients. For colonoscopy adherence among patients eligible for surveillance, 74.0% (94/127) of IRGI patients and 31.0% (97/313) of non-IRGI patients were adherent to all recommended postresult surveillance (P < .0001). For EGD adherence, 89.3% (50/56) of IRGI patients and 40.9% (61/149) of non-IRGI patients were adherent (P < .0001). Across the cohort, IRGI patients were more likely to be adherent to colonoscopy (OR, 7.40 [95% CI, 4.07 to 14.0], P < .0001) and EGD (OR, 7.32 [95% CI, 2.92 to 21.2], P < .0001). Attending IRGI was associated with higher adherence to surveillance guidelines among individuals with LS. Additional efforts are required to increase clinic attendance or otherwise improve adherence among patients with LS.

Mepifilina (mepyramine-acefyllinate) is a long-authorized legacy combination medicine in Spain for bronchoconstriction associated with acute/chronic bronchitis and remains reimbursed by the Spanish National Health System (SNS). We triangulated publicly accessible clinical evidence, GINA/GOLD/NICE/GEMA/GesEPOC mentions and pharmacological-class positioning, aggregate SNS dispensing/expenditure for ATC5 R03DA12, and regulatory auditability. A secondary, exploratory, non-validated Evidence-Practice Structural Misalignment (EPSM) rubric was used only as a transparency aid. Three randomized trials were identified (1994-2002; n=214); none evaluated the licensed indication, two were at high risk of bias, and certainty was very low. No guideline explicitly mentioned mepifilina; xanthines/theophylline had limited, later-line or conditional roles. During 2022-2024, SNS dispensing totaled 6.30 million packages (&#x20ac;27.87 million), with no public historical evaluation report available. Aggregate, non-clinical data do not permit inference on indication, duration, prescribing appropriateness, benefit or real-world safety. Findings support prioritizing proportionate reassessment; they do not establish clinical ineffectiveness, excess harm, inappropriate prescribing, overuse or withdrawal.

Current guidelines recommend screening for primary aldosteronism (PA) only in patients with hypertension and/or hypokalemia. However, recent evidence raises the question of whether normotensive patients with adrenal incidentalomas (AIs) might also exhibit biochemical features of aldosterone dysregulation. This study aimed to evaluate the prevalence and clinical significance of aldosterone-related abnormalities in normotensive patients with AIs. We retrospectively analyzed 452 patients with AIs, of whom 202 were normotensive. Hormonal evaluation included plasma aldosterone concentration (PAC) and either plasma renin activity or concentration. The aldosterone-to-renin ratio (ARR) was considered elevated if&#x2009;>&#x2009;20 when calculated with plasma renin activity or >&#x2009;1.8 when using direct renin concentration. We performed comparative analyses according to blood pressure (BP) status, PAC, ARR, and combined aldosterone phenotypes (PAC&#x2009;>&#x2009;10 ng/dL with elevated ARR, PAC&#x2009;>&#x2009;10 ng/dL with normal ARR, and PAC&#x2009;&#x2264;&#x2009;10 ng/dL with elevated ARR). Median follow-up was 3 years. Normotensive patients had a median age of 57 years (IQR 14), and 46.3% were male. Among them, 44.8% had PAC&#x2009;>&#x2009;10 ng/dL and 33.3% had an elevated ARR. Serum potassium levels were within the normal range (median 4.3 mmol/L, IQR 0.5). In normotensive patients, no significant differences in systolic or diastolic BP were observed according to PAC or ARR alone. In the overall cohort, diastolic BP was higher in patients with elevated ARR. Importantly, diastolic BP differed significantly across combined aldosterone phenotypes (p&#x2009;=&#x2009;0.015), with higher values observed in patients with PAC&#x2009;>&#x2009;10 ng/dL and elevated ARR compared with those with PAC&#x2009;>&#x2009;10 ng/dL and normal ARR (adjusted p&#x2009;=&#x2009;0.048). During follow-up, incident hypertension was numerically higher among ARR-positive normotensive patients (18.4% vs. 11.0%), although this difference did not reach statistical significance (p&#x2009;=&#x2009;0.215). A total of 10 patients were diagnosed with confirmed PA, including two normotensive individuals. Biochemical evidence of aldosterone dysregulation is common in patients with AIs, including normotensive individuals. While isolated elevations in PAC or ARR were not associated with significant BP differences, the coexistence of elevated PAC and ARR identified a subgroup with a more pronounced hemodynamic profile. These findings support the concept of a continuum of aldosterone excess and suggest that combined biochemical phenotypes may be more informative than isolated markers. Further prospective studies are needed to clarify the clinical implications of these findings and to define optimal screening strategies in this population.