Growth hormone deficiency (GHD) is a rare endocrine disorder responsible for growth failure. In the absence of an identified secondary cause, a genetic etiology can be identified, affecting genes involved in hypothalamo-pituitary growth hormone (GH) regulation or in pituitary development itself. The anterior pituitary gland arises from the oral ectoderm and is regulated by neuroectodermal signaling and transcription factors that ensure proper differentiation of hormone-producing cells. GH secretion is stimulated by growth-hormone-releasing hormone (GHRH) and ghrelin, with mutations in their respective receptors (GHRHR, GHSR) contributing to isolated GHD (IGHD). Mutations in GH1, encoding GH itself, are the main genetic cause of IGHD. GHD can also arise from mutations in transcription factor genes such as POU1F1, PROP1, IGSF1 or TBX19 or in genes involved in early brain development such as GLI2, LHX3 or HESX1, potentially leading to syndromic presentations with multi-organ involvement. Understanding the genetic basis of GHD is essential to improving diagnostic strategies, genetic counseling and the development of targeted therapies. Although animal models have been fundamental for understanding pituitary ontogenesis, emerging tools such as human pituitary organoids now offer the promise of dissecting human-specific regulatory mechanisms that cannot be fully captured in traditional animal models. This review aims to provide a comprehensive overview of all known genetic causes of GHD, with a particular focus on the underlying molecular mechanisms and their associated phenotypes.
Anaphylaxis during pregnancy is a rare but potentially life-threatening condition for both mother and fetus, requiring rapid recognition and immediate treatment. Although the fundamental mechanisms of anaphylaxis in pregnancy are similar to those in nonpregnant women, physiological adaptations of pregnancy, peripartum exposures, and fetal considerations substantially complicate diagnosis, management, and prevention, contributing to variability in care and avoidable adverse outcomes. In this multidisciplinary review, experts in allergy-immunology, obstetrics, anesthesiology, and epidemiology synthesize current evidence on the epidemiology, triggers, pathophysiology, diagnostic challenges, management, outcomes, and prevention of anaphylaxis throughout pregnancy, labor, and delivery. We highlight how gestational cardiovascular and respiratory changes may obscure classic diagnostic features, emphasize the safety and critical importance of prompt intramuscular epinephrine use as first-line therapy, and review maternal and fetal outcomes associated with timely versus delayed intervention. Strategies for risk stratification, allergology workup, prevention of recurrence, and implementation of coordinated care pathways are discussed. This review underscores the need for increased awareness, structured interdisciplinary collaboration, and integration of prevention-focused strategies across obstetric and allergy care. By providing a practical, evidence-based framework, it aims to support health professionals in optimizing diagnosis, management, and maternal-fetal safety when anaphylaxis occurs during pregnancy.
Surgical management of spinal metastases aims to palliate symptoms but poses significant perioperative risks. Traditional tools like survival scores and comorbidity indices inadequately capture the multidimensional frailty in cancer patients, prompting interest in frailty indices for risk stratification. This meta-analysis evaluates the predictive value of frailty indices for postoperative outcomes in spinal metastasis surgery. Adhering to PRISMA guidelines, PubMed, Embase, Cochrane Library, and other databases were systematically searched until May 2025. Observational clinical studies reporting frailty indices and postoperative outcomes (complications, LOS, nonroutine discharge, and survival rate) in spinal metastasis surgery were included. Study quality was assessed via Newcastle-Ottawa Scale. Pooled odds ratios (ORs) were calculated using fixed-effect model. A total of 12 studies involving 17,446 patients were included. The predictive value of several frailty indices, such as the 5-item/ 11-item modified frailty index (mFI-5/mFI-11), Metastatic Spinal Tumor Frailty Index (MSTFI), and Johns Hopkins Adjusted Clinical Groups (JHACG), were assessed. Some of the frailty indices predicted adverse outcomes: prolonged LOS (mFI-5 OR = 1.67, p = 0.014; JHACG OR = 2.65, p < 0.001), nonroutine discharge (MSTFI OR = 1.59, JHACG OR = 1.79; all p < 0.001), and complications (mFI-11 OR = 2.94, p = 0.003; MSTFI OR = 1.42, p < 0.001; JHACG OR = 1.54, p < 0.001). Survival prediction was inconsistent; only MSTFI correlated with 30-day mortality in one study (p < 0.05). Synthesized evidence from observational studies suggests that frailty indices were potential prognostic factors to predict post-operative morbidity, LOS, and discharge complexity. However, survival prognostication remains limited by tumor biology variability and methodological heterogeneity. Future efforts should integrate frailty assessments with tumor-specific factors to enhance prognostic precision and guide personalized perioperative optimization.
Despite the higher lung cancer incidence among Black individuals, existing evidence on racial disparities in smoking-related lung cancer risk remains limited. This review aims to examine differences in smoking-related lung cancer risk between Black and White individuals. We conducted a systematic review and meta-analysis of U.S.-based observational studies from 1964 to June 2024. Eligible studies examined lung cancer incidence as the primary outcome and reported race-specific estimates for smoking-related risk. Meta-analysis was used to compare lung cancer risk across racial groups by smoking status (current/former/ever vs. never). Of 460 abstracts screened, 36 met inclusion criteria, and 11 articles were included in the meta-analysis. Individuals who currently smoke had greater odds of developing lung cancer compared to those who never smoked (OR = 15.52 (95% CI 13.98-17.23)). Similarly, individuals who formerly smoked had greater odds of developing lung cancer compared to those who never smoked (OR = 6.36 (95% CI 5.73-7.07)). In the weighted meta-analysis model, we did not demonstrate significant odds of incident lung cancer cases by race, irrespective of smoking status. Our findings did not provide statistical evidence of a difference in smoking-related lung cancer risk by race, though precision was limited, particularly for Black participants. Future research should evaluate pack-years and other risk factors to elucidate differences in smoking behaviors among high-risk populations.
This study aims to systematically review and perform a single-arm meta-analysis to comprehensively evaluate the effect of removal of intraluminal stent from the Paul glaucoma implant (PGI) on intraocular pressure (IOP) changes and to summarize its long-term efficacy and safety. Glaucoma remains one of the leading global causes of irreversible vision loss, necessitating effective surgical management for refractory cases. Glaucoma drainage devices (GDDs) are critical for these complex forms, and intraluminal stent removal from the PGI serves as a key strategy to titrate aqueous outflow and optimize long-term IOP control. A systematic review was conducted by searching EMBASE, Medline, and CENTRAL. The meta-analysis ultimately included 5 observational studies. The Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool was used to assess the quality of the included studies. Continuous outcomes (e.g., post-removal stent IOP reduction) were analyzed using the mean difference (MD) with 95% confidence intervals (CI); dichotomous outcomes (e.g., hypotony incidence) were evaluated using pooled proportion with 95% CI. All meta-analyses employed a random-effects model. Our meta-analysis included 5 studies, involving a total of 283 eyes. The meta-analysis revealed that removal of the stent leads to a significant and immediate IOP reduction. The IOP reduction (immediate post-removal stent IOP minus pre-removal stent IOP) was significant, with a pooled mean difference of -9.09 mmHg IOP [mean difference (MD) = 9.09; 95% confidence interval (CI) = (-11.77, -6.41)]. In the pre-removal stent high-IOP (>21 mmHg) subgroup, the IOP reduction is -11.82 [95% CI = (-10.14, -13.51)]. This reduction was significantly greater than the pre-removal stent low-IOP (<21 mmHg) subgroup, whose reduction is -6.66 mmHg [95% CI = (-5.55, -7.77)]. Regarding safety, the pooled proportion of clinically hypotony was low and highly consistent (I² =0.00%) at only 0.03 [95% CI = (0.00, 0.15)]. Intraluminal stent removal from the PGI is an effective and safe IOP-lowering intervention. Its IOP reduction effect is significantly more pronounced in patients with pre-removal stent high IOP, providing crucial clinical guidance for managing persistently high IOP after PGI implantation.
The role of age diversity has increased attention in organizations with the focus of collaboration between younger and older employees. The present study aims to investigate the perceptions of younger generation towards others with respect to organizational commitment, trust and job satisfaction in the healthcare field, particularly in nursing. A quantitative survey was conducted to collect data from 696 working young professionals in nursing within the healthcare sector in Pakistan. Structural equation modeling was employed to examine the relationships among the variables using Smart-PLS Software version 4.1.0.9. The obtained results show that the perceptions of working professionals from Generation Z with respect to generational stereotyping, positive effect and inclusiveness about other generations are positively correlated with trust and job satisfaction by mediating role of organizational commitment in the nursing sector. Research highlights perception of Generation Z at workplace impacted on trust, satisfaction, and commitment and closely connected to improved quality of work life. The study contributes to the existing literature on nursing management of intergenerational interactions. It advocates for redesigning systems to focus on development and well-being within the nursing sector.
Student-led community health service opportunities are commonly offered by nursing schools to improve student's educational and non-academic skills. However, evidence on their implementation and impact remains limited. The article aims to synthesise the implementation strategies of nursing student-led community health services and to evaluate the impact of these services on nursing students' learning outcomes and the health outcomes of service recipients. A mixed-methods systematic review using data-based convergent synthesis was performed. Searches were conducted across nine databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was used. Forty-six studies were included. Student nurses and faculty members were the key service providers, critical in facilitating a collaborative community-academic partnership. The services targeted individuals with varying healthcare needs. Student's learning outcomes could be mapped into i) personal growth, ii) awareness of social issues and iii) professional knowledge and skills development. Positive impacts on clinical outcomes, health knowledge, and healthcare service utilization among service recipients were reported. Student-led community health services positively impact both student learning and community health outcomes. Their reciprocal benefits make them both valuable additions to nursing education. Future research could explore technology-driven approaches to scale these services globally.
This study aims to develop biodegradable chitosan-based films containing Chlorella vulgaris biomass and tannic acid, and to further enhance the optimized matrix through the incorporation of juniper seed (Juniperus excelsa) extract (EX). The effects of EX incorporation were evaluated relative to both the baseline chitosan film and the optimized extract-free matrix film in terms of functional, antioxidant, antibacterial, thermal, and structural properties. Distinct from conventional chitosan-based films, the present work applies a mixture-design optimization strategy to a chemically complex algae-chitosan system, enabling systematic evaluation of multicomponent interactions rather than one-factor-at-a-time modifications. The film formulation was optimized using a D-optimal mixture design, with algae (ALG) (15-45%), chitosan (CH) (30-55%), glycerol (GLY) (20-45%), and tannic acid (TA) (0-15%) as independent variables and tensile strength (TS), elongation-at-break (EAB), elastic modulus (EM) and water vapor permeability (WVP) as the response parameters. The validated film (V) containing 29.7% ALG, 43.3% CH, 25% GLY, and 2% TA, showed TS of 5.72 ± 0.36 MPa, EAB of 20.07 ± 1.58%, EM of 25.96 ± 2.51 MPa, and WVP of 0.24 ± 0.02 g.mm/m2.h.kPa. The optimized film was then supplemented with EX at 5%, 10%, and 15% (v/v), yielding VEX5, VEX10, and VEX15 films, respectively. Spectroscopic and thermal analyses revealed enhanced intermolecular interactions among chitosan, microalgal components, tannic acid, and juniper seed extract polyphenols, including hydrogen bonding and π-π associations, leading to a more cohesive polymer network and improved thermal stability compared to the baseline chitosan film, as evidenced by shifts in degradation-related thermal events. Scanning Electron Microscopy (SEM) observations showed a progression from smooth surfaces in the control chitosan film to increasingly compact morphologies in extract-loaded samples, with VEX15 exhibiting the most uniform structure. Antibacterial assays of film-forming solutions against Staphylococcus aureus, Escherichia coli, and Salmonella Typhimurium revealed increasing inhibition zones with higher EX content, indicating a synergistic effect with algal and polyphenolic components. Overall, the algae-chitosan-glycerol-tannic acid film system enriched with J. excelsa extract offers improved structural stability, antioxidant potential, environmentally responsive degradability, and functional performance, highlighting its potential for sustainable packaging.
2-Ethylhexyl salicylate (EHS), homomenthyl salicylate (HMS), and ethylhexyl methoxycinnamate (EHMC) are three commonly used organic ultraviolet filters (OUVFs) that exhibit environmental persistence and bioaccumulation potential. They are widely distributed in surface water, wastewater, sediment, soil, air, and dust, as well as in organisms. Their concentrations vary significantly across matrices, spatiotemporal scales, and species. In surface water, the concentrations of the three OUVFs are notably higher in industrial and tourist-influenced waters, with the mean concentration of HMS reached 215.4 ng/L at Waikiki Beach and EHS averaged 203 ng/L along Romania's Black Sea coast. In wastewater, EHMC occurred at hundreds of ng/L in the dissolved phase, while its particulate-phase concentration peaked at 65,500 ng/g. Their atmospheric concentrations are predominantly in the pg/m3 range, with median values reaching hundreds of pg/m3. Moreover, OUVF concentrations in urban soils remain relatively elevated in soils of industrial areas. Their mean bioaccumulation factors (BAFs) were 1432 L/kg for EHS, 21,642 L/kg for HMS, and 447 L/kg for EHMC, with HMS posing the greatest ecological risk. These three OUVFs elicit diverse toxic effects (e.g., endocrine disruption, plant growth inhibition) and exert compound-specific toxicity through five core pathways: the hypothalamic-pituitary-thyroid (HPT) axis, hypothalamic-pituitary-gonadal (HPG) axis, oxidative stress, lipid metabolism, and apoptosis. Their environmental risks show distinct spatiotemporal and species-specific differences, with maximum exposure risk quotients (RQex) of 33 for EHS and 22 for HMS in summer along the western Mediterranean coast. Considerable uncertainties remain regarding their environmental occurrence, toxicological mechanisms and risk assessment. This paper aims to review the pollution characteristics, ecotoxicity and risk profiles of the three compounds to inform future studies and regulatory decision-making.
In the era of biologic therapy, the management of severe asthma is evolving towards personalized medicine frameworks that integrate clinical, functional, and biological traits. In this narrative review, we explore the convergence of Treatable Traits and Treat-to-Target principles within a unified concept known as Treat-to-Target by Treatable Traits (T4) Framework. The T4 Framework introduces an innovative methodology for the management of severe asthma through a trait-oriented and target-focused paradigm. We propose a conceptual approach that emphasizes remission as a realistic and clinically meaningful target, but that must be sought through a tailored approach to the multiple heterogeneous features of the disease. This T4 Framework aims to streamline treatment strategies, enhancing patient outcomes by addressing the specific characteristics of severe asthma and facilitating a more effective management pathway. Implementing the T4 Framework may significantly improve the personalization of asthma management, ultimately leading to better control and quality of life for patients with severe asthma.
Kinesin family member 4A (KIF4A) regulates chromosome condensation and segregation during mitosis and is upregulated as an oncogene in various malignancies. However, its role in gastric cancer (GC) remains unclear. Therefore, this study aims to evaluate the clinicopathological and prognostic significance of KIF4A expression in GC. KIF4A protein expression was assessed via immunohistochemistry and quantified using QuPath-based digital image analysis. KIF4A expression was analyzed for its associations with clinicopathological and molecular characteristics, as well as its prognostic significance. Additionally, bioinformatics tools were used to confirm the prognostic value of KIF4A at the mRNA level and perform enrichment and comprehensive immune analyses. Low KIF4A expression was significantly associated with adverse clinicopathological features and inversely correlated with HER2 amplification. Survival analysis revealed that patients with low KIF4A expression had poor clinical outcomes, consistent with mRNA-level analyses from publicly available databases. Univariate Cox regression revealed low KIF4A expression as a significant prognostic factor. However, low KIF4A expression was no longer significant in multivariate analysis. In enrichment analysis, low KIF4A expression is associated with EMT activation, whereas high expression correlates with E2F-mediated proliferation. Although high KIF4A expression suggests an immune-inflamed phenotype, its predictive ability was limited in an independent validation cohort.
Lysosomes, as a key acidic organelle which was responsible for intracellular degradation and recycling, often intercept small-molecule drugs or nanoparticle drugs, limiting the therapeutic efficacy of cancer. To overcome this barrier, lysosomal rupture has emerged as a novel phototherapy strategy due to its noninvasive and spatiotemporally controllable nature. This review provides a comprehensive summary of photosensitive materials capable of modulating lysosomal membrane permeability upon light irradiation, focusing on two primary categories: nanomaterials and small molecules. These lysosome-targeting photosensitive materials can trigger multiple cell death pathways (apoptosis, necrosis, pyroptosis, and ferroptosis) by photodynamic or photothermal therapy, thereby enhancing drug escape and activating cell death cascades. The review aims to offer theoretical insights for optimizing tumor drug delivery efficiency and achieving precise lysosome-mediated tumor cell death.
Adaptive deep brain stimulation (aDBS) for Parkinson's disease (PD) aims to improve treatment efficacy by adjusting stimulation amplitude based on a neurophysiological feedback signal reflecting the patient's clinical state. Although beta band (± 13-35 Hz) spectral power from local field potential (LFP) recordings is the best-characterized physiomarker to-date, correlations with motor symptom severity remain modest. To explore whether combining spectral information from multiple frequencies improves explained variance in motor symptom severity, we applied canonical correlation analysis (CCA) to the full power spectral density (1-100 Hz) of LFP recordings from 67 patients with PD undergoing subthalamic nucleus DBS, alongside clustered and individual items of the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (UPDRS-III). CCA redundancy indices quantified that over 20% of variance in UPDRS-III scores was explained by a linear combination of spectral power across frequencies, compared to ~10% by beta power alone. Beta frequencies contributed most strongly and positively to total UPDRS-III scores, with slightly stronger contributions of low-beta (~13-25 Hz) than high-beta (~26-35 Hz) ranges. Low-frequency (<10 Hz) and finely-tuned gamma activity at half the stimulation frequency (62-63 Hz) contributed negatively. Symptom-specific analyses revealed a clear double beta peak associated with bradykinesia, while rigidity was primarily associated with low-beta power. Tremor showed a less distinctive spectral pattern. CCA results were highly similar for contralateral and ipsilateral symptoms. Overall, CCA findings revealed both shared and symptom-specific spectral patterns underlying PD motor symptoms and demonstrate the added value of a broader spectral physiomarker.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia globally, marked by chaotic electrical impulses and irregular atrial contraction. At the cellular level, defective calcium (Ca+2) handling plays a central role in AF pathogenesis, with the sarco/endoplasmic reticulum Ca+2-ATPase (SERCA) pump being a critical determinant of intracellular Ca+2 reuptake and myocardial relaxation. Recent research has uncovered a class of small transmembrane micropeptides, phospholamban (PLB), sarcolipin (SLN), dwarf open reading frame (DWORF), myoregulin (MLN), endoregulin (ELN) and another-regulin (ALN), that directly modulate SERCA activity. Interestingly, these micropeptides exhibit chamber-specific expression and diverse regulatory mechanisms, functioning as inhibitors, uncouplers or facilitators of SERCA activity and are increasingly linked to atrial arrhythmogenesis. This review synthesizes current understanding on function of SERCA micropeptides, highlighting their distinct roles in atrial versus ventricular excitation-contraction (E-C) coupling. We explore evidence from genetically modified animal models and patient-derived data to elucidate how dysregulation of these peptides, particularly SLN and PLB, contributes to abnormal EC-coupling like Ca+2 cycling, delayed afterdepolarizations, oxidative stress and atrial remodeling. We also examine the influence of systemic metabolic regulators, such as thyroid hormones, catecholamines, dexamethasone and various exercise paradigms on micropeptide expression and function, offering insight into their intersection with AF progression. By dissecting the spatial, temporal and metabolic regulation of SERCA micropeptides, this review aims to offer current understanding about chamber-specific modulation of Ca+2 homeostasis and use these insights towards treatment of AF.
Mutational falsetto is a functional voice disorder identified by the persistence of a high-pitched voice in males after puberty. It causes mild dysphonia and a range of vocal symptoms, including high-pitched falsetto voice, low intensity, cul-de-sac nasality, and breathiness. Voice therapy is often the first intervention used to reduce these symptoms. This review aims to investigate the effectiveness of different voice therapy techniques in individuals diagnosed with mutational falsetto. A comprehensive literature search was conducted across several electronic databases, including PubMed/MEDLINE, ScienceDirect, SCOPUS, and Google Scholar. To find relevant articles, several key terms, such as voice therapy, mutational falsetto, puberphonia, and speech therapy were used. Studies published in English that investigated the effects of various voice therapy techniques on individuals with mutational falsetto and their "abstract" and "full text" were related to mutational falsetto were included. A total of 11 articles, which were accessible and relevant to the review's focus, were included in this review. The majority of these studies focused on the impact of an eclectic voice therapy approach, combining techniques such as yawn-sigh, glottal fry, laryngeal manipulation, inspiratory phonation, and humming, on multidimensional voice outcomes. However, one study focused on manual therapy as a physiologic voice therapy approach. Findings demonstrated the positive effects of voice therapy on multiple aspects of vocal function, with nearly all parameters of voice quality improving following the intervention (P < 0.05). Voice therapy techniques, using various approaches, are considered the first line of intervention for improving the quality of voice production in patients with mutational falsetto. These techniques have led to significant improvements in multiple aspects of voice. However, further research is needed to determine which approach or technique is most effective. Future studies with larger sample sizes, standardized methodologies, follow-up assessments, and the use of more novel assessment methods and parameters are essential to strengthen the evidence regarding the effectiveness of voice therapy in this population.
Allogeneic transplantation is a cornerstone treatment for hematologic malignancies and organ failure, yet its success is limited by graft-versus-host disease (GvHD) and allograft rejection. Conventional broad-spectrum immunosuppression compromises protective graft-versus-leukemia (GvL) effects and anti-infectious immunity, creating an urgent need for precision tolerance strategies. CD4+Foxp3+ regulatory T cell (Treg)-directed strategies offer a promising solution but expanding stable, functional Tregs ex vivo and in vivo remains challenging. Given the pivotal role of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF) in Treg biology, this review aims to critically examine how its members control Treg function and how these pathways can be leveraged for Treg‑based therapies. We systematically analyze key TNFRSF members - TNFR2, OX40, CD40, Fas, CD27, 4-1BB, GITR, and DR3 - detailing their dichotomous roles in Treg function and translational potential. We highlight how agonism of TNFR2 or DR3 offers selective Treg expansion while preserving GvL activity, and how CD27 and 4-1BB serve as valuable markers for isolating highly suppressive Treg subsets. We further discuss translational challenges, including the paradoxical effects of OX40 and GITR, which can either enhance or impair Treg function depending on the inflammatory milieu, and the vulnerability of Tregs to Fas-mediated apoptosis during ex vivo expansion. We also discuss CD40-CD40L blockade as a complementary strategy to empower endogenous Tregs. By synthesizing current knowledge, this review provides a rational roadmap for using selective agonism, blockade, or phenotypic selection to bolster Treg‑based therapies for GvHD, offering practical information for both laboratory and clinical efforts to optimize Treg manufacturing and achieve durable tolerance.
Pediatric renal stone surgery aims to achieve complete stone clearance with minimal perioperative morbidity. Mini-percutaneous nephrolithotomy (mini-PCNL) is widely used for larger stones, yet factors influencing postoperative residual fragments and bleeding risk in children are not fully clarified. This study evaluated outcomes after pediatric mini-PCNL and identified predictors of residual fragments and bleeding-related morbidity in a large single-center cohort. This single-center retrospective cohort included 371 renal units in children treated with mini-PCNL (2011-2024) using 14-20 French (Fr) access sheaths. Stone-free rate (SFR) was defined as 0-mm residual fragments on 1-month kidney-ureter-bladder (KUB) radiography and ultrasonography (US). Computed tomography (CT) was not routinely performed and was obtained only when clinically indicated, which may have resulted in underestimation of very small residual fragments. Multivariable logistic regression evaluated predictors of 1-month residual fragments and bleeding-related morbidity. One-month SFR was 79.2% (294/371) and increased to 88.4% (328/371) by 3 months after auxiliary procedures. Staghorn morphology was associated with residual fragments (aOR 5.01, 95% CI 1.86-13.51); operative time was also associated (aOR 1.12 per 10-minute increase, 95% CI 1.04-1.20). Complications occurred in 12.9%, mainly low-grade according to the Clavien-Madadi classification, with no grade IV-V events. Transfusion was required in 2.2% (8/371). Bleeding-related morbidity increased with operative time (aOR 1.16 per 10-minute increase, 95% CI 1.07-1.25). Compared with 14 Fr, 20 Fr demonstrated a nonsignificant trend toward higher odds of bleeding-related morbidity (aOR 3.20, 95% CI 0.93-11.05), whereas 16 Fr showed no statistically significant association (aOR 1.75, 95% CI 0.56-5.47). With a stringent 0-mm stone-free definition, mini-PCNL provided high clearance rates and low major morbidity in this large pediatric cohort. Staghorn stones remained the strongest predictor of residual fragments. Prolonged operative time was consistently associated with increased bleeding-related morbidity, while the use of 20 Fr access demonstrated only a modest, nonsignificant elevation in bleeding risk.
This study aims to determine the course of immunosuppressive medication adherence (MA) in individuals who have undergone kidney transplantation for over a decade and to identify the demographic and clinical factors affecting this adherence. This retrospective and cross-sectional descriptive study evaluated the biological adherence of 103 kidney transplant recipients (KTRs) at 12 different time points using tacrolimus and cyclosporine blood levels. Self-reported adherence was assessed via The Immunosuppressant Therapy Adherence Scale. Associations between adherence and demographic and clinical variables were also analyzed. The mean time since transplantation was 11.77 ± 1.46 years. Biologically, 43.3% of patients had low MA. In contrast, self-reported adherence was 82.52%. No statistically significant correlation was found between biological and self-reported adherence outcomes. Patients with low biological adherence presented increased blood urea nitrogen (BUN) levels at 6 months and 9 years post-transplant. Similarly, patients with low self-reported adherence had increased BUN levels at 10 years. Self-reported adherence scores were significantly lower among patients with a history of graft rejection (p < 0.001). No significant associations were found between MA and variables such as sex, donor type, or age (p > 0.05). This study identifies significant discrepancies between biological and self-reported methods for evaluating long-term adherence to immunosuppressive therapy. The results indicate that adherence fluctuates over time, highlighting the need for multidimensional assessment strategies. The implementation of standardized, and complementary tools is crucial to improving graft and patient survival. Future multicenter research should investigate pre-transplant predictors to optimize long-term medication adherence.
Yield estimation significantly contributes to oil refineries, especially for the newcomer crude oil, and concurrently diminishes the sole dependency on laboratory analysis. Implementing simulation modelling, Aspen HYSYS, for designing distillation unit operations has improved yield prediction. This paper aims to simulate a distillation column using Aspen HYSYS V14 software to estimate the yield of crude oil without specification of product flowrate. Three crude oils from the actual refinery data were applied and compared in understanding the factors affecting yield flowrate and column temperature profiles, such as the crude oil feed flowrate, bottom steam flowrate, and column pressure (top and bottom). The developed model has successfully predicted the yield of crude oil with a comparable error, demonstrating a minimum temperature profile error ranging from 0.07% to 1.04% (except for the bottom column), and deviations of 1.60% to 20.48% for flowrate across three samples. The parameter evaluation found that a higher bottom steam flowrate would reduce the light and medium products by 2% and increase the heavy products by approximately 5%. A higher pressure of the top column significantly affects flowrate of kerosene by the increment of ~ 2.45%, while the increase of bottom pressure slightly reduces the products flowrate, especially, for the heavier range.
This article aims to highlight proteinuria and nephrotic syndrome as significant yet under-recognized adverse events of VEGF pathway inhibition by tyrosine kinase inhibitors (TKIs), illustrated in the treatment of radioiodine-refractory differentiated thyroid cancer. This report presents a case of recurring (nephrotic range) proteinuria in a patient with radioiodine-refractory differentiated thyroid cancer treated sequentially with lenvatinib, sorafenib and cabozantinib. In the discussion, an overview of the existing literature is provided through a PubMed search. Reported incidence of proteinuria varies across VEGFR-targeted TKIs in clinical trials. However, direct comparisons between agents should be interpreted cautiously. The underlying pathophysiology is multifactorial, involving hypertension, endothelial injury, and direct podocyte damage, often resulting in focal segmental glomerulosclerosis, minimal change disease or non-thrombotic hyaline glomerular microangiopathy. Timely recognition and monitoring are essential, as early discontinuation or dose adjustment can lead to partial or full reversibility of renal damage. Switching to TKIs with a different nephrotoxic profile may be a feasible strategy to maintain oncological benefit while minimising renal risk. Nonetheless, given the limited evidence, this approach requires cautious implementation in selected cases. Proteinuria and nephrotic syndrome are an important class effect of VEGFR-directed TKIs. Regular monitoring, early detection, and timely dose adjustments or treatment switches are essential to minimize irreversible renal damage while maintaining oncological benefit.