The discontinuation of the CS2 version of the semi-automated CliniMACS Plus device in 2024 prompted validation of a CD34+ immunoselection process using the fully automated CliniMACS Prodigy (Miltenyi Biotec). This transition was leveraged to evaluate Prodigy's performance on thawed apheresis products. Results were compared with fresh donor apheresis previously processed on the CliniMACS Plus and, within this validation, with fresh products processed on Prodigy. Fresh apheresis products from rhG-CSF-mobilized related donors were processed using either device. Cryopreserved apheresis products intended for destruction were thawed (Viathaw, Cytiva), washed on Sepax-II and resuspended in MACS GMP PBS/MgCl₂ with HSA and rh-DNase prior to CD34+ selection on Prodigy. Flow cytometry (Stem Kit-Beckman Coulter) was used for CD34+ and CD45+ cell quantification. From fresh products, immunoselections yielded similar CD34+ purities (95% versus 97%) and viabilities (95% versus 99%) for CliniMACS Plus (n = 10) and Prodigy (n = 10), respectively. T-cell depletion was slightly better with the CliniMACS Plus (0.1 × 10⁴ versus 0.4 × 10⁴ CD3⁺/kg), while CD34+ recovery was more efficient with Prodigy (66% versus 53%). Processing thawed apheresis with the Prodigy archieved 98% CD34+ purity, 51% recovery, and 0.3 × 10⁴ CD3⁺/kg, all within our center's acceptance criteria. The fully automated workflow significantly reduced hands-on time (2 h versus 5 h) and operator intervention. Prodigy platform enables reproducible CD34+ immunoselection from both fresh and thawed products, improving standardization, efficiency, and flexibility in graft engineering and ATMP manufacturing. The ability to process thawed products also broadens clinical options whenever cryopreserved products are available.
We used 2020-2022 data from the MACS/WIHS Combined Cohort Study (MWCCS) of 1689 women with and without HIV to identify latent health behavior classes (HBCs) underlying covariation in diet, physical inactivity, and substance use. We tested if HBCs predicted key mental and physical health outcomes, including depression and metabolic syndrome (MetS), at a 1-year follow-up. A latent class analysis yielded three HBCs: (1) Class 1: Healthiest, (2) Class 2: Poor Diet with Substance Use, and (3) Class 3: Physical Inactivity and Poor Diet with Low Substance Use. Women with older age, higher income, and HIV had greater odds of being in Class 1. Class 2 had the highest odds of elevated depressive symptoms when controlling for age, income, menopause stage, and HIV status. Although Class 3 had the highest odds of MetS, the association between HBC and MetS was nonsignificant. Findings suggest complex health behavior patterns predict depressive symptoms.
HIV has transitioned into a chronic condition often accompanied by multimorbidity, including type 2 diabetes (T2D). Women with HIV (WWH) and T2D face elevated risks for depression, loneliness, and reduced social support. Pain-a common and burdensome symptom in both conditions-remains underexamined despite its potential to exacerbate psychosocial challenges and diminish quality of life. We conducted a cross-sectional analysis using data from the MACS/WIHS Combined Cohort Study (MWCCS), focusing on the Women's Interagency HIV Study (WIHS) subset. Self-reported measures included pain status (dichotomized as yes/no) and mental health outcomes (depressive symptoms, loneliness, social support, and quality of life). Clinical variables included HIV serostatus, diabetes status, hemoglobin A1c, and body mass index. Generalized linear regression models assessed associations between pain and mental health outcomes, adjusting for demographic and clinical covariates. Among 2,410 participants, 72% identified as Non-Hispanic Black, 10% as Non-Hispanic White, 15% as Hispanic, and 4% as other; mean age was 47.4 years (SD = 9.3) and BMI 31.8 (SD 8.9). Seventy-one percent were HIV seropositive, 19% had diabetes, and 67% reported pain. Overall, participants reported moderate social support (mean = 57.1, range 15-75), with higher scores among women with diabetes (mean = 66.3) compared to those without diabetes (mean = 57.3). HIV status did not significantly influence social support. Fully adjusted models revealed strong associations between pain and all mental health outcomes (p < 0.001). Women reporting pain had higher depressive symptoms (B = 7.59; 95% CI: 6.68, 8.49), greater loneliness (B = 0.80; 95% CI: 0.65, 0.94), lower social support (B = - 5.37; 95% CI: -6.64, - 4.10), and markedly lower quality of life (B = - 23.44; 95% CI: -24.87, - 22.01) compared to women without pain. No significant interactions were observed by HIV or diabetes status. Pain is strongly associated with worse psychosocial outcomes among women in WIHS, regardless of HIV or diabetes status. These findings highlight the need for integrated, patient-centered interventions that address pain alongside mental health and social support to improve quality of life for women with multimorbidity. Future research should explore longitudinal patterns and tailored strategies to mitigate the compounded burden of pain and psychosocial distress.
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Macrophages play an important role in kidney inflammation and fibrosis. Circulating biomarkers of macrophage activation are elevated in people with HIV (PWH). We therefore determined their associations with kidney function and chronic kidney disease (CKD) risk in people with and without HIV. We analyzed data from 2 prospective cohorts: the Women's Interagency HIV Study and Multicenter AIDS Cohort Study. Serum concentrations of soluble (s)CD14, sCD163, galectin-3 (Gal-3) and Gal-3 binding protein (Gal-3BP) were measured between 2004 and 2006. We examined each biomarker's association with estimated glomerular filtration rate (eGFR) using multivariable linear regression and with incident CKD (2 consecutive eGFR <60 mL/min/1.73 m2) using cause-specific Cox proportional hazards models, adjusting for sociodemographics, CKD risk factors, and HIV-related factors. Among 1284 participants, 61% were women, 70% were PWH, of whom 59% were virally suppressed (HIV RNA < 200 copies/mL); median eGFR was 93 mL/min/1.73 m2 at baseline. All macrophage biomarker concentrations were higher in PWH versus without HIV (P < .05). Cross-sectionally, higher concentrations of sCD14 and Gal-3 were independently associated with lower eGFR (P < .001). Over a median follow-up of 14.2 years, incident CKD occurred in 23% of PWH and in 11% without HIV. Each standard deviation higher concentration of sCD14 and Gal-3BP was independently associated with 22% and 29% increased CKD risk, respectively. Associations for sCD163 and Gal-3 were attenuated after multivariable adjustment. Findings were similar in analyses restricted to PWH. Macrophage activation may mark and/or contribute to CKD development. Studies are needed to determine whether targeting immune activation improves kidney health in PWH.
This study aimed to compare body composition measurements between patients with nonfunctional adrenal incidentalomas (NFAI) and mild autonomous cortisol secretion (MACS) using bioelectrical impedance analysis (BIA) and anthropometric methods. This cross-sectional study included patients diagnosed with MACS or NFAI. Body composition was assessed using BIA, anthropometric measurements, and the Durnin and Womersley (DW) method. Correlation and Bland-Altman analyses were performed to assess the relationship and agreement between the DW method and BIA. Fifty-seven patients (32 with MACS and 25 with NFAI) were included; those with MACS were older (p = 0.004). Post-dexamethasone suppression test cortisol levels (p < 0.001) and the incidence of bilateral tumors (p = 0.017) were higher in MACS patients. No significant differences in body composition parameters were observed between the MACS and NFAI groups. A strong correlation was observed between BIA- and DW-derived fat mass in MACS patients (r = 0.890, p < 0.001). Bland-Altman analysis revealed a slight mean bias for body fat mass of -0.4 kg (limits of agreement: -9.14-8.34 kg) and for body fat percentage of -0.83% (limits of agreement: -11.32-9.66%) between methods. A robust correlation and acceptable agreement was demonstrated between the DW method and BIA for estimating body fat. The DW equation may provide a practical and low-cost alternative for assessing body composition in MACS and NFAI cohorts. Limitations include the lack of a healthy control group and the inability to validate BIA and anthropometric estimates against gold-standard imaging techniques, potentially introducing accuracy bias.
Patients with mild autonomous cortisol secretion (MACS) have higher rates of vertebral fractures compared to patients with non-functioning adrenal nodules, yet bone density is not always reduced. To characterize the effect of MACS on bone density, metabolism, and microstructure as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Cross-sectional study, 2019-2022. Tertiary referral center. 75 patients with MACS and 75 age-, sex-, and gonadal status matched referent subjects. Bone turnover markers, dual-energy x-ray absorptiometry (DXA) scan, and HR-pQCT. Areal and volumetric bone mineral density (aBMD, vBMD), trabecular bone score (TBS), microstructural parameters including trabecular bone volume to total volume (BV/TV) ratio. While no differences in aBMD were observed at any skeletal site, patients with MACS had decreased TBS (1.389 vs 1.475, P < 0.001) and lower osteocalcin concentration (17.1 vs 19.5 ng/mL, P = 0.030) than referent subjects. On HR-pQCT at the tibia, patients with MACS had reduced trabecular BV/TV (0.220 vs 0.233, P = 0.015) compared to referent subjects. On multivariable analysis, MACS was associated with lower TBS (OR per SD decrease 2.87 [1.65-5.00]), lower trabecular BV/TV at the radius (OR per SD decrease 2.58 [1.33-5.00]), and lower trabecular BV/TV at the tibia (OR per SD decrease 4.06 [2.10-7.86]). Patients with MACS have microstructural deterioration that may not be evident on routine DXA aBMD testing.
Autologous chimeric antigen receptor (CAR) expressing T-Cells (CAR-T) have been efficiently used in hematological malignancies but their efficacy in solid tumors remains limited. CAR therapies via the use of macrophages, offer a promising avenue due to their unique ability to infiltrate tumors and to initiate phagocytosis. To generate a preclinical model of CAR-Macs, we have designed a novel CAR-construct to target EGFRVIII-expressing glioblastoma cells (DK-MG) using THP-1 monocytic cell line able to differentiate towards macrophages. The CAR structure comprises a ScFv recognizing specifically EGFRVIII and MEGF10 intracellular domain which enhances tethering and phagocytosis activity. THP-1 cell line expressing CAR and control constructs were generated via lentiviral transduction followed by generation of monocytes and CAR-expressing M1 macrophages (CAR-Macs). To evaluate their ability of phagocytosis, we co-cultured THP-1 derived WT macrophages or CAR-Macs in the presence of target DK-MG cells. Confocal microscopy experiments revealed highly efficient phagocytosis of DK-MG EGFRVIII cells by CAR-Macs (~ 60%) as compared to WT cells (~ 15%). The killing potential of the anti-EGFRVIII CAR-Macs against the glioblastoma cell line has also been observed using video microscopy. ELISA and LDH assays performed in co-culture supernatants, showed an increase of IL-6 and LDH levels suggesting efficient cytotoxicity via CAR-Macs. Transcriptome analyses performed in purified CAR-Macs, revealed evidence of a molecular signature in favor of successful phagocytosis. The model described in this work is suitable for allowing translation to iPSC-derived macrophages to generate clinically applicable future cell therapy approaches in solid tumors expressing mutated variant EGFRVIII.
During chronic liver injury, danger signals released by damaged hepatocytes are known to sequentially promote the polarization of monocyte-derived macrophages (Mo-Macs) toward a pro-fibrotic phenotype and activate hepatic stellate cells (HSCs), ultimately leading to hepatic fibrosis (HF). Intracellular endoplasmic reticulum (ER) stress, tightly associated with dysregulated calcium ion (Ca2+) flux and excessive reactive oxygen species (ROS) production, is recognized as a key driver of this pro-fibrotic polarization process. Recently, metal-polyphenolic networks (MPNs) have garnered significant attention as a versatile class of nanomedicines for treating various diseases, with their potential for tailored design and functional modification, as well as the stimuli-responsive delivery of natural polyphenols and metal ions. In this study, exploiting the ability of magnesium ions (Mg2+) to suppress ER Ca2+ release and tannic acid (TA) to scavenge ROS, we fabricated Mg-TA MPN-based nanomedicines aimed at restoring ER homeostasis for the treatment of HF. The resulting PEGylated formulation, Mg-TA-PEG (MTP), exhibited excellent biocompatibility, pH-responsive dissociation, and efficient hepatic accumulation. Intravenous MTP administration significantly attenuated carbon tetrachloride induced HF in mice, as evidenced by reduced collagen deposition, normalized liver architecture, and improved metabolic function. Single-nucleus RNA sequencing analysis revealed that MTP inhibits the induction of Mo-Macs by damaged hepatocytes, alleviates ER stress in Mo-Macs, and shifts their polarization from a fibrosis-promoting phenotype to immuno-suppressing and regeneration-promoting phenotypes. This reprogramming further modulates paracrine signaling from Mo-Macs to HSCs, reverting HSCs from an activated to a quiescent state. Moreover, in vitro cell coculture experiments confirmed that MTP primarily targets Mo-Macs rather than directly inhibiting HSC activation, underscoring the central role of Mo-Macs in MTP mediated fibrosis resolution. Together, these findings elucidate the anti-fibrotic mechanism of MTP nanomedicines and highlight a promising strategy for reprogramming Mo-Mac phenotypes to treat HF.
Mild autonomous cortisol secretion (MACS) is characterized by cortisol excess without overt Cushing's syndrome. While metabolic complications are well-documented, the psychological burden remains incompletely understood. This study aimed to assess self-reported depressive and anxiety symptoms and health-related quality of life in MACS patients using validated Turkish instruments and compare findings with Turkish population norms. This cross-sectional study included 40 MACS patients (34 women, 6 men; mean age 56.3±9.3 years) from 45 newly diagnosed patients (3 excluded as per exclusion criteria, 2 declined). MACS was diagnosed according to European Society of Endocrinology guidelines. As part of institutional protocol, psychological assessments were routinely performed at diagnosis for all newly diagnosed patients. Assessments included Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Short Form-36 (SF-36) using validated Turkish versions. Mean BDI category score was 1.93±0.80 (minimal to mild depressive symptoms) and mean BAI category score was 2.30±0.82 (mild anxiety symptoms). SF-36 scores were significantly lower than Turkish population norms across all domains except emotional well-being (p < 0.001 for all significant domains except bodily pain, p = 0.012). Subgroup analysis by post-dexamethasone cortisol levels showed no significant differences in psychological parameters. MACS patients exhibit impaired quality of life across most SF-36 domains compared to Turkish population norms, despite only mild self-reported depressive and anxiety symptoms. Although limited by the absence of a matched control group and potential confounding by metabolic comorbidities, these findings suggest that psychological screening and quality of life assessment may be valuable in MACS evaluation.
Alcohol use disorder (AUD) is a chronic relapsing disorder with high early rehospitalization rates. Valid instruments assessing dependence severity, craving, and relapse risk are fundamental for follow-up. The aim of this study was to examine the psychometric properties of the Hungarian Severity of Alcohol Dependence Questionnaire (SADQ), Multidimensional Alcohol Craving Scale (MACS), Penn Alcohol Craving Scale (PACS) and Alcohol Relapse Risk Scale (ARRS), and test their utility in predicting relapse risk and rehospitalization. Ninety-three AUD inpatients were assessed on hospitalization day 8 with SADQ, AUDIT, MACS, PACS, visual analogue scale (VAS) of craving and ARRS, and followed for 3 months. Internal consistency and concurrent validity were evaluated. We tested whether SADQ and ARRS predicted 3-month rehospitalization (logistic regressions), whether MACS and PACS predicted relapse risk (linear regression). The 3-month rehospitalization rate was 21.5%. All scales showed high internal consistency (α = 0.86-0.94) and concurrent validity. After item reduction based on item-total correlations, the 27-item ARRS (ARRS-27) showed higher internal consistency, and predicted rehospitalization (OR = 1.12, 95% CI: 1.05-1.18; p < 0.001). Higher SADQ scores predicted rehospitalization (OR = 1.05, 95% CI: 1.02-1.09; p = 0.007). MACS (p < 0.001) and PACS (p = 0.046) scores predicted ARRS scores (R2 = 0.53), with MACS showing the stronger effect. Based on our preliminary results, the Hungarian SADQ, MACS, PACS, and ARRS-27 are reliable instruments with predictive value for relapse risk and rehospitalization in AUD. Their combined use might support a treatment and relapse-prevention algorithm, improving clinical care and guiding future research.
Background/Objectives: Mild autonomous cortisol secretion (MACS) is increasingly recognized in patients with adrenal incidentalomas. While associated with cardiometabolic risk, management strategies remain controversial, particularly regarding functional outcomes. This retrospective comparative cohort study evaluated the impact of adrenalectomy versus conservative management on muscle strength in MACS patients. Materials and Methods: Forty patients with MACS (1-mg dexamethasone suppression test > 1.8 µg/dL) were enrolled: 15 underwent adrenalectomy and 25 received conservative management. Hand grip strength was measured using calibrated dynamometry, and gait speed was assessed with the 1-m walk test at baseline and 6 months. Results: Baseline characteristics are summarized descriptively for the surgical and conservative cohorts. At 6 months, the surgery group showed significant improvements in right hand grip strength (+1.19 ± 0.64 kg, p < 0.001) and left hand grip strength (+1.15 ± 0.49 kg, p < 0.001), representing approximately 5% improvement. In contrast, the conservative group exhibited significant decreases in strength over the same period (right: -0.40 ± 0.25 kg; left: -0.28 ± 0.28 kg, both p < 0.001). The post-surgical 1-mg dexamethasone suppression test decreased from 4.05 ± 1.44 to 1.01 ± 0.34 µg/dL (p < 0.001). Conclusions: Adrenalectomy results in significant improvement in objective muscle strength in MACS patients, with improvement observed in parallel to biochemical resolution of cortisol excess. In contrast, conservative management was associated with progressive decline in grip strength over 6 months. Hand grip dynamometry provides valuable functional outcome data that may guide surgical decision-making in MACS management.
Osteal macrophages ("osteomacs") are resident bone macrophages that support osteoblast differentiation and bone formation. Despite their importance in bone homeostasis, their function in human bone metabolism and osteoporosis remains poorly understood, largely due to the lack of a standardized isolation protocol. Here, we present a protocol for isolating primary human osteomacs from femoral head specimens obtained during arthroplasty. After the removal of bone marrow to minimize contamination with marrow-derived macrophages, bone fragments were enzymatically digested and osteomacs were isolated using CD14-based MACS® or CD14/CD45/ALP-based FACS. Immunofluorescence confirmed macrophage identity and revealed expression of markers associated with both M1-like and M2-like activation states. Isolated cells displayed heterogeneous morphology and could be maintained in culture. This protocol enables reproducible isolation of human osteomacs and provides a foundation for translational studies investigating osteoimmune interactions in bone disease and osteoporosis.
To determine the interrater reliability and stability of the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS)/Mini-MACS, and Communication Function Classification System (CFCS) in individuals with STXBP1- and SYNGAP1-related disorders. Data were collected from 83 individuals with STXBP1-related disorders (34 females, 49 males; mean age = 9 years 10 months) and 101 individuals with SYNGAP1-related disorders (51 females, 50 males; mean age = 10 years 11 months) who participated in a prospective natural history study with both cross-sectional and longitudinal phases. Two raters completed the GMFCS, MACS/Mini-MACS, and CFCS assessments on the same day; test-retest stability was evaluated for participants with two longitudinal assessments. Interrater agreement varied from 73.8% to 77.3% for the STXBP1-related disorder cohort and from 60.5% to 83.3% for the SYNGAP1-related disorder cohort. Interrater reliability weighted kappa scores for the STXBP1-related disorder cohort varied from 0.83 to 0.93, while scores for the SYNGAP1-related disorder cohort ranged from 0.66 to 0.81. Test-retest stability scores for the STXBP1-related disorder group varied from 0.62 to 0.94, while scores for the SYNGAP1-related disorder group ranged from 0.38 to 0.78. Significant correlations were found between all assessment scales for both STXBP1-related disorders (Kendall's tau range from 0.25 to 0.42) and SYNGAP1-related disorders (Kendall's tau range from 0.19 to 0.45). The GMFCS, MACS/Mini-MACS, and CFCS demonstrate appropriate levels of interrater reliability and stability for individuals with STXBP1- and SYNGAP1-related disorders.
Mild autonomous cortisol secretion (MACS) is associated with impaired glucose metabolism, but the metabolic effects of adrenostatic therapy in this setting remain unclear. This study aimed to explore whether changes in CGM-derived glycaemic metrics could be observed during timed evening metyrapone administration in patients with MACS. This prospective, single-centre interventional study included nine patients with MACS due to adrenal adenoma or hyperplasia and coexisting prediabetes or untreated mild type 2 diabetes. Participants underwent continuous glucose monitoring (CGM) for one week at baseline and for one week during treatment with the 11β-hydroxylase inhibitor metyrapone (500 mg at 6:00 PM and 250 mg at 10:00 PM). Morning (8:00 AM) serum cortisol, ACTH levels and parameters of glucose metabolism were assessed. Data distribution was evaluated using the Shapiro–Wilk test; paired comparisons were performed using appropriate parametric or non-parametric tests, with correction for multiple comparisons. After one week of metyrapone treatment, the percentage of time with glucose levels between 70 and 140 mg/dL (time-in-tight-range, TITR) increased from 81% to 84% (p < 0.05). Time in range (70–180 mg/dL) increased from 98.4% to 99.4%, while time above range (> 180 mg/dL) decreased from 1.4% to 0.1% (both p < 0.05). ACTH concentrations increased, while morning cortisol levels remained stable. After short-term evening administration of metyrapone a modest yet statistically significant change in CGM-derived glycaemic metrics was observed in patients with MACS, without altering morning cortisol levels. These findings support the need for further studies to evaluate the long-term metabolic effects of adrenostatic therapy in this population.
Maternal-assisted caesarean section (MACS) is a modified approach to caesarean section. The patient scrubs and gowns with their surgeon, and following the delivery of the baby's head, the mother helps assist the delivery of her baby from her abdomen onto her chest. The aim of MACS is to improve the birth experience, mother-baby bonding, breastfeeding rates, and provide control and agency during the process of elective caesarean section. Patient demand has increased alongside public awareness of the procedure. Here we outline a protocol to perform MACS to guide other clinicians on how to safely incorporate it into their own practice.
Less adults with cerebral palsy (CP) lives independently, compared to adults without disabilities. Access to personal assistance may help overcome barriers to independent living. Also, little is known about hand function in adults with CP, and the role of hand function in achieving independent living remains unexplored. To explore the associations between housing and personal assistance in adults with CP, relative to their hand function, age and sex. We conducted a cross-sectional registry-based study of 2304 adults with CP, aged 20-64 years old, from the Swedish CP Follow-up Program and Quality Registry. Logistic regression models were used to estimate odds ratios (ORs). Almost half (48%) of the adults with CP lived independently, and 35% lived with their parents. Independent living was strongly associated with hand function, age and access to personal assistance. The probability of independent living decreased with increasing MACS levels. The odds for independent living increased with access to personal assistance (OR 13.6, 95% CI 9.5-19.6), age (OR 1.09, 95% CI 1.08-1.10), and was higher in women (OR 1.3, 95% CI 1.0-1.5) than men. In total, 995 (43%) adults received personal assistance. The probability for assistance increased successively with MACS levels to MACS V (OR 5.31, 95% CI 4.79-6.96). Hand function and access to personal assistance are key predictors of independent living in adults with CP. Promoting hand function and ensuring adequate assistance are essential for improving autonomy and quality of life in adults with CP.
The granuloma serves not only as a physical barrier to restrict the dissemination of intracellular pathogens but also functions as a complex immune microenvironment. However, the bioenergetics and regulatory mechanisms maintaining this architecture remain elusive in vertebrates. Here, integrating multi-tissue transcriptomics, single-cell RNA sequencing (scRNA-seq), ultrastructural imaging, and fluorescence in situ hybridization (FISH) in a largemouth bass (Micropterus salmoides)-Nocardia seriolae infection model, we resolved the metabolic and functional landscape of the granuloma. We found that across multiple tissues (head kidney, spleen, liver, kidney), the host initiates a synchronized transcriptional program that promotes macrophage differentiation into specialized epithelioid macrophages (E-Macs). Notably, E-Macs concurrently upregulated specific transporters and metabolic enzymes (e.g., laao, slc6a8), as well as oxidative phosphorylation (OXPHOS) and glycolysis genes, accompanied by mitochondrial proliferation. Functionally, E-Macs shifted from a pro-inflammatory to an immunoregulatory and pro-survival phenotype, characterized by high expression of protease inhibitors (e.g., csta) and anti-apoptotic factors (e.g., bcl2l14, ywhag1). Comparative analysis in zebrafish confirmed these metabolic and regulatory signatures are evolutionarily conserved. In conclusion, this study reveals a host survival strategy of immune regulation underpinned by metabolic adaptation, providing novel perspectives for controlling chronic granulomatous diseases in aquaculture.
To systematically evaluate the impact of adrenal tumour diagnosis and targeted interventions on health-related quality of life (HRQoL) and neuropsychiatric outcomes across tumour subtypes. Systematic review. A literature search of MEDLINE, Embase, Cochrane Library, and CINAHL (January 1990-March 2026) identified studies reporting HRQoL and neuropsychiatric outcomes in adults with adrenal tumours, including non-functioning adrenal tumours (NFAT), mild autonomous cortisol secretion (MACS), adrenal Cushing's syndrome (CS), primary aldosteronism (PA), phaeochromocytoma/paraganglioma (PPGL), and adrenocortical carcinoma (ACC). Study quality was assessed using CONSORT-PRO and Newcastle-Ottawa criteria. Due to methodological heterogeneity, findings were synthesized narratively. A total of 117 studies involving 35 361 patients were included. CONSORT-PRO quality was good but heterogeneous, whereas observational study quality was mostly moderate or low. Across tumour subtypes, adrenal tumours were consistently associated with impaired HRQoL and neuropsychiatric outcomes. A gradient of burden was evident, with mild impairment in NFAT, intermediate impairment in MACS and PA, and the most pronounced and persistent deficits in adrenal CS, PPGL, and ACC. Targeted interventions were often associated with improved patient-reported outcomes, though the magnitude and consistency of benefit varied across tumour subtypes and study design. Recovery was frequently incomplete. Most studies relied on generic HRQoL instruments, and no disease-specific neuropsychiatric tools were identified. Adrenal tumours are associated with substantial and often persistent impairment in patient well-being across tumour subtypes. Although treatment generally improves outcomes, residual symptoms are common, underscoring the need for long-term, patient-centred care and for the development of adrenal tumour-specific patient-reported outcome measures.
Mild Autonomous Cortisol Secretion (MACS) is associated with cardiometabolic comorbidities, but the benefit of adrenalectomy remains controversial. We retrospectively reviewed patients undergoing adrenalectomy between October 2019 and October 2024. MACS was defined as post-1 mg dexamethasone suppression test cortisol 1.8-5.0 μg/dL without overt Cushing's syndrome. Pre- and postoperative clinical and biochemical outcomes were analyzed. Thirty-eight patients met inclusion criteria (median age 64 years; 60.5% female). Median post-DST cortisol was 2.9 μg/dL, with a median follow-up of 258 days. Significant postoperative improvements were observed in systolic (p = 0.001) and diastolic (p = 0.004) blood pressure, HbA1c (p = 0.013), and antihypertensive medication burden (p = 0.009). General health status, HbA1c and number of antihypertensive medications improved in 76.3%, 58.4% and 52.8% of the patients, respectively. Clinical outcomes did not differ between patients with cortisol levels <2.5 vs. ≥2.5 μg/dL. Adrenalectomy in selected MACS patients is associated with improvements in blood pressure, glycemic control, and overall health, independent of preoperative cortisol levels.