Search Results (40)

Background/Objectives: Hypothyroidism is highly prevalent among HD patients, due to cumulative disturbances in thyroid hormone synthesis, metabolism, and clearance. Subclinical hypothyroidism—defined by elevated TSH with normal fT₄—is common in HD, along with a distinct entity, the low-T₃ syndrome. This study aims to examine the predictors of hypothyroidism in HD and its impact on cardiovascular morbidity and mortality. Methods: We conducted a retrospective cohort study including 282 hemodialysis (HD) patients, with evaluated thyroid function and monitored from January 2022 to June 2025. A total of 66 (23.4%) patients with hypothyroidism were identified, 15 (5.31%) of whom had autoimmune thyroiditis. Subclinical hypothyroidism was documented in 31.81% of the hypothyroid patients. Results: Hypothyroidism occurred predominantly in females (63.63% vs. 41.2%, p ≤ 0.001) and was associated with higher BMI (27.856 ± 6.216 vs. 25.759 ± 6.080, p = 0.017), hypoalbuminemia (3.534 ± 0.547 vs. 3.725 ± 0.471, p = 0.006), elevated LDL-cholesterol and triglyceride levels, as well as with amiodarone use. Hypothyroidism was further associated with atrial fibrillation (33.33 vs. 19.9%, p = 0.022), coronary artery revascularization procedures (18.18% vs. 9.72%, p = 0.047), neoplastic disease (25.75% vs. 12.03%, p = 0.008), and cancer-related mortality (10.6% vs. 1.85%, p = 0.001). Multivariable regression analysis revealed the following predictors of hypothyroidism: female sex (OR 3.848, 95%CI 1.704–8.693, p = 0.001), BMI (OR 1.072, 95%CI 1.007–1.146, p = 0.031), hypoalbuminemia (OR 0.412, 95%CI 0.177–0.962, p = 0.040), hypertriglyceridemia (OR 1.088, 95% CI 1.001–1.016, p = 0.022) and amiodarone use (OR 6.698, 95%CI 1.744–25.722, p = 0.006). Patients with autoimmune thyroiditis did not exhibit clinical or biochemical differences compared with other hypothyroid patients. Subclinical hypothyroidism was associated with longer HD duration (10.476 ± 7.910 vs. 6.567 ± 5.541, p = 0.003), dyslipidemia, hypertension, atrial fibrillation and amiodarone use. Cardiovascular conditions—particularly atrial fibrillation and ischemic coronary disease requiring revascularization—are more common in HD patients with clinical or subclinical hypothyroidism. However, in our cohort, the Kaplan–Meier survival curves at 12, 24, and 36 months for patients with both subclinical and clinical hypothyroidism do not show significant differences in cardiac or overall mortality. Conclusions: The increased incidence of hypothyroidism in HD patients, together with its impact on cardiovascular pathology, underscores the need for multidisciplinary management and supports annual routine assessment of thyroid hormones—particularly in overweight or dyslipidemic patients and in those receiving amiodarone. Full article

Aim: Nephrotic syndrome (NS) represents a complex glomerular disorder with significant clinical heterogeneity across pediatric and adult populations. Although glucocorticosteroids have constituted the mainstay of therapeutic intervention for more than six decades, primary treatment resistance manifests in approximately 20% of pediatric patients and 50% of adult cohorts. Steroid-resistant nephrotic syndrome (SRNS) is associated with substantially greater morbidity compared to steroid-sensitive nephrotic syndrome (SSNS), characterized by both iatrogenic glucocorticoid toxicity and progressive nephron loss with attendant decline in renal function. Based on this, the current study aims to develop a robust machine learning (ML) model integrated with explainable artificial intelligence (XAI) to distinguish SRNS and identify important biomarker candidate metabolites. Methods: In the study, biomarker candidate compounds obtained from proton nuclear magnetic resonance (1 H NMR) metabolomics analyses on plasma samples taken from 41 patients with NS (27 SSNS and 14 SRNS) were used. We developed ML models to predict steroid resistance in pediatric NS using metabolomic data. After preprocessing with MICE-LightGBM imputation for missing values (<30%) and standardization, the dataset was randomly split into training (80%) and testing (20%) sets, repeated 100 times for robust evaluation. Four supervised algorithms (XGBoost, LightGBM, AdaBoost, and Random Forest) were trained and evaluated using AUC, sensitivity, specificity, F1-score, accuracy, and Brier score. XAI methods including SHAP (for global feature importance and model interpretability) and LIME (for individual patient-level explanations) were applied to identify key metabolomic biomarkers and ensure clinical transparency of predictions. Results: Among four ML algorithms evaluated, Random Forest demonstrated superior performance with the highest accuracy (0.87 ± 0.12), sensitivity (0.90 ± 0.18), AUC (0.92 ± 0.09), and lowest Brier score (0.20 ± 0.03), followed by LightGBM, AdaBoost, and XGBoost. The superiority of the Random Forest model was confirmed by paired t-tests, which revealed significantly higher AUC and lower Brier scores compared to all other algorithms (p < 0.05). SHAP analysis identified key metabolomic biomarkers consistently across all models, including glucose, creatine, 1-methylhistidine, homocysteine, and acetone. Low glucose and creatine levels were positively associated with steroid resistance risk, while higher propylene glycol and carnitine concentrations increased SRNS probability. LIME analysis provided patient-specific interpretability, confirming these metabolomic patterns at individual level. The XAI approach successfully identified clinically relevant metabolomic signatures for predicting steroid resistance with high accuracy and interpretability. Conclusions: The present study successfully identified candidate metabolomic biomarkers capable of predicting SRNS prior to treatment initiation and elucidating critical molecular mechanisms underlying steroid resistance regulation. Full article

Background: Long QT syndrome (LQTS) is characterized by delayed myocardial repolarization, predisposing to malignant arrhythmias such as torsades de pointes, ventricular fibrillation, and cardiac arrest. Recent reports suggest that acquired LQTS (aLQTS) may represent an early manifestation of hypopituitarism, potentially contributing to its increased cardiovascular mortality, although evidence remains limited to 16 published case reports. Objective: The objective was to investigate the relationship between hypopituitarism and corrected QT (QTc) interval. Methods: We retrospectively analyzed data from 185 patients (121 males) with hypothalamic–pituitary disorders who underwent a 12-lead electrocardiogram between April 2023 and September 2024. Clinical characteristics, hormone replacement therapy, and same-day laboratory parameters (electrolytes, fT3, fT4, IGF-I, testosterone) were recorded. QTc was calculated using Bazett’s formula. Multivariate logistic regression identified predictors of QTc prolongation. Results: Age (OR 1.07–1.09, p = 0.02) was a significant predictor in 5 of 8 models. The presence of expansive lesions other than pituitary adenomas, craniopharyngiomas, and Rathke’s cleft cysts was also associated with QTc prolongation (OR 8.35–17.73, p < 0.05 and p = 0.03). Potassium (OR 0.14–0.17, p = 0.09) and albumin-corrected calcium levels (OR 0.0003, p = 0.06) showed consistent, though borderline, associations. Conclusions: Age and the presence of expansive lesions other than pituitary adenomas, craniopharyngiomas, and Rathke’s cleft cysts are the main predictors of QTc duration in patients with hypothalamic–pituitary disease. Electrolyte imbalances—particularly low potassium and albumin-corrected calcium—may further contribute. The influence of specific pituitary deficiencies remains uncertain, likely due to adequate replacement therapy in most patients. Full article

Background: Treosulfan combined with fludarabine (FluTreo) has emerged as a reduced-toxicity alternative to conventional myeloablative conditioning in allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) and related myeloid malignancies. Purpose: This study evaluates the safety, engraftment kinetics, and long-term outcomes of the FluTreo FT14 regimen in a real-world adult cohort. Materials and Methods: We conducted a prospective cohort study of 186 consecutive adults (18–70 years) undergoing allo-HCT between January 2015 and December 2024. Eligible diagnoses included de novo or secondary AML, myelodysplastic syndrome, and myelofibrosis. All received peripheral blood stem cells from matched or mismatched unrelated donors, HLA-matched siblings, or haploidentical relatives. The FT14 protocol comprised fludarabine 150 mg/m² over five days and treosulfan 42 g/m² over three days, with rabbit antithymocyte globulin (5 mg/kg) for unrelated grafts. Primary endpoints were neutrophil and platelet engraftment, donor chimerism, incidence of acute and chronic graft-versus-host disease (GVHD), overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM). Kaplan–Meier, Cox regression, and Fine and Gray models were applied. Results: Median age was 59 years; diagnoses included de novo AML (43%), secondary AML (16%), MDS (25%), and MF (16%). Neutrophil and platelet engraftment medians were 10 and 12 days, respectively. Full donor chimerism (≥99%) was achieved by day 31. Grade III conditioning-related toxicity occurred in 3.2% of cases. Five-year cumulative incidences of grade II–IV acute GVHD and moderate/severe chronic GVHD were 37.6% and 30.6%. Median follow-up was 16.3 months; relapse occurred in 25.3%. Five-year OS and DFS were 71% and 49% overall (75.8% and 59% in CR1), with TRM of 15.3%. Disease relapse and acute GVHD independently predicted inferior OS, and acute GVHD predicted TRM. Conclusions: The FluTreo FT14 regimen achieves rapid engraftment, universal high donor chimerism, low severe toxicity, and durable survival, supporting its use as a myeloablative, reduced-toxicity conditioning option in myeloid malignancies. Full article

Background/Objectives: High-frequency ultrasonography (HFUS) has gained increasing attention in dermatology as a non-invasive imaging technique capable of visualizing cutaneous structures with high resolution. In cutaneous T-cell lymphomas (CTCL), including mycosis fungoides (MF)/Sézary syndrome (SS), HFUS may provide an objective method for assessing disease activity and monitoring treatment response. This study aimed to evaluate the clinical utility of HFUS in detecting therapy-induced changes in subepidermal low-echogenic band (SLEB) thickness. Methods: We conducted a prospective, single-center study between May 2021 and May 2025. Thirty-three patients with histologically confirmed MF (n = 31) or SS (n = 2) underwent HFUS at baseline and after 4–8 weeks of treatment. SLEB thickness was measured before (E1) and after early treatment (E2). Patients received systemic agents, phototherapy, or topical regimens. Statistical analysis included mixed-model ANOVA with repeated measures to assess SLEB changes, and post hoc tests were applied to explore the influence of therapy type, age, and gender. Results: Among 31 evaluable patients with MF, HFUS revealed a significant reduction in SLEB thickness after treatment (0.90 ± 1.10 mm vs. 0.69 ± 0.89 mm; F(1,29) = 8.88, p = 0.006, η² = 0.23). The type of early therapy (systemic vs. topical) did not significantly affect outcomes (p = 0.452). Age emerged as a relevant factor: patients ≥ 66 years exhibited higher baseline SLEB values and a significant reduction post-treatment (p < 0.001), whereas no comparable effect was observed in younger patients. Gender did not significantly influence SLEB changes. Conclusions: HFUS is a sensitive and clinically applicable imaging tool for monitoring treatment response in MF/SS. Reductions in SLEB thickness were observed across therapeutic modalities and aligned with early clinical improvement. HFUS may serve as a valuable adjunct to standard clinical and histopathological evaluation in the routine management of MF/SS. Full article

Background: Thyroid dysfunction, including non-thyroidal illness syndrome (NTIS), is commonly observed in critically ill patients and has been reported in COVID-19, particularly in those with severe disease. NTIS is defined by low free triiodothyronine (fT3) with normal or low thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels. Thyroid autoantibodies may also reflect immune system activation. The relationship between thyroid hormone alterations, autoimmunity, and clinical severity in COVID-19 remains incompletely understood. Methods: We conducted a retrospective study of 276 patients hospitalized with COVID-19, including 138 in the intensive care unit (ICU) and 138 in general wards. A control group of 110 hospitalized, non-infected patients was also analyzed. Serum concentrations of TSH, fT3, fT4 and reverse T3 (rT3) were measured. The presence of anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-Tg), and thyrotropin receptor antibodies (TRAb) was assessed. Results: NTIS was observed in 44.2% of ICU patients, 18.1% of non-ICU patients, and 1.8% of controls. The fT3/rT3 ratio was lowest in ICU patients (median 0.11 vs. 0.16 in non-ICU and 0.22 in controls). Thyroid autoantibodies were significantly more prevalent in COVID-19 patients than in controls, with anti-TPO antibodies being the most frequently detected. Their presence, even in patients without known thyroid disease, may reflect immune activation associated with SARS-CoV-2 infection. Conclusions: NTIS and thyroid autoimmunity are frequent in hospitalized COVID-19 patients and may reflect disease severity and immune activation. Our study highlights the prognostic relevance of routine thyroid testing, including the fT3/rT3 ratio and combined autoantibody positivity (notably the triple-positive pattern), by directly comparing ICU and non-ICU patients with a non-COVID control group. Full article

Background: Monocarboxylate-transporter-8-(MCT8) deficiency, or Allan–Herndon–Dudley syndrome (AHDS), is a rare X-linked disorder caused by pathogenic variants in the SLC16A2 gene, leading to impaired transport of thyroid hormones, primarily T3 and T4, across cell membranes. The resulting central hypothyroidism and peripheral hyperthyroidism cause neurodevelopmental impairment and thyrotoxicosis. Despite the availability of therapy options, e.g., with triiodothyroacetic acid (TRIAC), diagnosis is often delayed, partly due to normal TSH levels or incomplete genetic panels. MCT8 deficiency is not yet included in newborn-screening programs worldwide. Case Description: We present a case of an infant genetically diagnosed with MCT8 deficiency at 5 months of age after presenting with muscular hypotonia, lack of head control, and developmental delay. Thyroid function testing revealed a normal TSH, low free T4, and significantly elevated free T3 and free T3/T4 ratio. Treatment with TRIAC (Emcitate^®) was initiated promptly, with close drug monitoring. Despite persistent motor deficits and dystonia, some developmental progress was observed, as well as reduction in hyperthyroidism. Discussion/Conclusions: This case underscores the importance of early free T3 and fT3/fT4 ratio testing in infants with unexplained developmental delay. Broader inclusion of SLC16A2 in genetic panels and consideration of newborn screening could improve early diagnosis and outcomes in this rare but treatable condition. Full article

Congenital hypothyroidism (CH) is a heterogeneous condition present at birth, resulting in severe-to-mild thyroid hormone deficiency. This condition is difficult to recognize shortly after birth. Therefore, many countries worldwide have implemented newborn screening (NBS) programs for CH since the 1970s. The most recent European guidelines strongly recommend screening for primary CH, as well as for central CH when financial resources are available. However, no consensus has been reached yet to screen more rare forms of CH, such as Allan–Herndon–Dudley syndrome (AHDS), an X-linked condition linked to mutations in the gene encoding a transmembrane monocarboxylate transporter (MCT8), resistance to thyroid hormone beta (RTHβ), and resistance to thyroid hormone alfa (RTHα). The combined measurement of thyroid-stimulating hormone (TSH) and total thyroxine (TT4) on DBS currently allows the recognition of central CH (TSH low/normal and low TT4 without defects in transport proteins). With the introduction of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for measurement of free triiodothyronine (FT3) and free thyroxine (FT4), it would be possible to screen for RTHβ (TSH normal/high and high FT4). More complicated would be the method to screen RTHα. It would require the combined measurement of FT4 and FT3 and the determination of FT3/FT4 ratio, while the combined measurement of FT3 and reverse T3 (rT3) to calculate FT3/rT3 ratio would be useful to screen AHDS. In this article, we provide some reflections on expanding NBS for primary CH also to other rare forms of CH. Full article

Background: Patients in Intensive Care Units (ICUs) often develop non-thyroidal illness syndrome. Potentially, thyroid hormones may be removed during continuous veno-venous hemodiafiltration (CVVHDF), as their molecular size is smaller than the filter pores’ cutoff. The study’s main aim was to assess whether the serum concentration of thyroid hormones changes over time during CVVHDF. Methods: This was a prospective observational trial that included 30 patients treated in an ICU. All patients developed acute kidney injury (AKI) and had clinical indications for implementation of CVVHDF. Blood samples were collected before initiation of CVVHDF and at 1, 2, 3, 6, 9 and 12 days after. The last sample was collected three days after CVVHDF withdrawal. Thyroid function was evaluated by determining the serum concentration of TSH, thyrotropin-releasing hormone (TRH), free triiodothyronine (fT₃), free thyroxine (fT₄), total triiodothyronine (tT₃), total thyroxine (tT₄) and reverse triiodothyronine (rT₃). We additionally calculated the total activity of peripheral deiodinases (G_D) using a mathematical model. Results: TRH and TSH levels remained mostly within normal ranges. fT4 and tT4 were in normal range or slightly below. In contrast, fT3 and tT3 were undetectably low in most patients throughout. Reverse T3 levels remained within normal limits. There were no statistically significant changes in any thyroid hormone levels over the CVVHDF treatment period. The calculated peripheral G_D activity was lower than normal, but importantly, it did not change significantly over time. Conclusions: Thyroid hormones are not lost due to hemodiafiltration. Decreased deiodinases activity is responsible for alterations in serum concentrations of thyroid hormones in patients during CVVHDF. Full article

Background/Objectives: The aim of this study is to develop a hybrid artificial intelligence (AI) approach to improve the accuracy, efficiency, and reliability of Down Syndrome (DS) risk prediction during first trimester prenatal screening. The proposed method transforms one-dimensional (1D) patient data—including features such as nuchal translucency (NT), human chorionic gonadotropin (hCG), and pregnancy-associated plasma protein A (PAPP-A)—into two-dimensional (2D) Aztec barcode images, enabling advanced feature extraction using transformer-based deep learning models. Methods: The dataset consists of 958 anonymous patient records. Each record includes four first trimester screening markers, hCG, PAPP-A, and NT, expressed as multiples of the median. The DS risk outcome was categorized into three classes: high, medium, and low. Three transformer architectures—DeiT3, MaxViT, and Swin—are employed to extract high-level features from the generated barcodes. The extracted features are combined into a unified set, and dimensionality reduction is performed using two feature selection techniques: minimum Redundancy Maximum Relevance (mRMR) and RelieF. Intersecting features from both selectors are retained to form a compact and informative feature subset. The final features are classified using machine learning algorithms, including Bagged Trees and Naive Bayes. Results: The proposed approach achieved up to 100% classification accuracy using the Naive Bayes classifier with 1250 features selected by RelieF and 527 intersecting features from mRMR. By selecting a smaller but more informative subset of features, the system significantly reduced hardware and processing demands while maintaining strong predictive performance. Conclusions: The results suggest that the proposed hybrid AI method offers a promising and resource-efficient solution for DS risk assessment in first trimester screening. However, further comparative studies are recommended to validate its performance in broader clinical contexts. Full article

Aim: This study aimed to investigate the effect of Euthyroid Sick Syndrome (ESS) on non-invasive mechanical ventilation (NIV) failure and in-hospital mortality. We also examined the impact of prolonged low fT3 levels before intensive care unit (ICU) admission on mortality and NIV failure. Methods: The study included 386 ICU patients who received NIV. The patients were categorized into two groups: those with ESS and those without (Non-ESS). Additionally, retrospective fT3 levels were examined in the ESS group over 6 months before ICU admission, and 61 patients with prolonged ESS were identified. The primary endpoints of this study (NIV failure and mortality) were compared between study groups. Results: Of the 386 patients included in the study, comprising 332 survivors and 54 deceased individuals, ESS was observed in 49.0% of the total patient population, with a significantly higher prevalence (p = 0.005) among deceased patients (66.7%) compared to survivors (46.1%). Among the 189 patients with low fT3 levels, there was a significant disparity between survivors and deceased patients (p < 0.001). Of these, 32.3% had low fT3 levels both before and during ICU admission (prolonged ESS), with 26.1% survivors and 58.3% deceased (p < 0.001). NIV failure was significantly more common in the ESS group (44.4%) than in the non-ESS group (26.4%; p < 0.001). Conclusion: Our study demonstrates that ESS, mainly characterized by low fT3 levels, was significantly associated with increased mortality rates in ICU patients and a higher failure rate of NIV. Full article

Background/Objectives: Cancer represents an important risk factor for acquiring severe acute respiratory syndrome by Coronavirus-2 (SARS-CoV-2) and subsequent hospitalization. The utility of early antiviral therapies, including their protective effect on long COVID outcomes, in cancer patients has not yet been clearly demonstrated. We conducted the CO.THER study (COVID-19 THErapies in patients with canceR) to address this knowledge gap. Methods: We designed an ambispective single-center cohort study. We collected clinical and oncological data from the hospital’s electronic patient records at the start of COVID-19 therapy (T0), seven days after T0 (T1), two weeks after T0 (T2), one month after T0 (T3), three months after T0 (T4), six months after T0 (T5), and twelve months after T0 (T6). The primary endpoint of this ambispective single-center cohort study was the rate of hospitalization for COVID-19 disease within 14 days in cancer patients using anti-SARS-CoV-2 early therapies. The proportion of hospitalizations within 14 days (primary endpoint) was computed together with its exact binomial 95% confidence interval (95%CI). Results: 131 patients’ records (53M [40.5%], 78F, [59.5%]; median age 62.45, interquartile range [IQR] 56–71) were enrolled. As shown by the Kaplan–Meier hospitalization-free estimate, only three patients (2.1%) were hospitalized for a COVID-19 related cause within 14 days of starting early treatment (95%CI 0.5–6.6%). The cumulative survival probability beyond 12 months in hospitalization-free patients was 98% (95%CI 93–99%). Twelve patients (9.2%) reported another COVID-19 infection during the follow-up and they were all retreated with Nirmatrelvir–Ritonavir. The cumulative reinfection-free survival was 90% at 12 months (95%CI 83–95%). Further, 15 patients of the 123 evaluable at 3 months (median age 51 years, IQR 40–68) reported long COVID symptoms (12.2%, 95%CI 7.0–19.3%). Conclusions: Our data demonstrate a low rate of hospitalization and reassuring data on safety in this cohort of high-risk subjects. Full article

Background: WFS1-spectrum disorders are caused by a mutation in the WFS1 gene. The term includes a wide range of rare disorders, from the most severe Wolfram syndrome with autosomal recessive inheritance to milder clinical manifestations with a single causative variant in the WFS1 gene, such as Wolfram-like syndrome, low-frequency sensorineural hearing loss (LFSNHL), isolated diabetes mellitus (DM), nonsyndromic optic atrophy (OA), and isolated congenital cataracts. Methods: The aim of this study was to evaluate genotype–phenotype correlations in Polish patients with WFS1-spectrum disorders. The study group constituted 22 patients (10 F; 12 M), including 10 patients (3 F; 7 M) referred to the Outpatient Clinic for Rare Diseases in Children and Adolescents and Diabetogenetics between 2019 and 2024 with clinical symptoms suggestive of WFS1-spectrum disorders, and 12 of their first-degree relatives (7 F; 5 M) from 10 families in Poland. Molecular testing was performed using tNGS (Targeted Next Generation Sequencing; Illumina) and analyzed for variants in the WFS1 gene. Results: Thirteen different variants in the WFS1 gene were found in 22 individuals (10 patients and family members), including the identification of two new variants (c.1535T>C and c.2485C>G). All patients had hyperglycemia or DM, hearing impairment, OA, or a combination of these symptoms. Four patients in the study group were diagnosed with Wolfram syndrome and all were compound heterozygotes for variants in the WFS1 gene. Conclusions: The evaluation of molecular characteristics in combination with clinical symptoms broadens the understanding of WFS1-spectrum disorders and allows more accurate management and prognosis for patients with this diagnosis. Full article

Baseline thyroid function, as measured by the fT3 to fT4 ratio, has been shown to influence the prognosis of advanced cancer patients receiving active treatments. Although immune checkpoint blockade can alter the balance of thyroid hormones, this interaction has not been thoroughly investigated. The present research sought to determine whether changes in the fT3/fT4 ratio could affect the survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) who were undergoing pembrolizumab-based therapies. This study included patients with metastatic NSCLC who received pembrolizumab as upfront treatment, either alone or in combination with platinum-based chemotherapy. Relevant data were gathered before the start (time point 1) and after 12 weeks (time point 2) of treatment. From April 2018 to May 2023, we enrolled 258 eligible patients, 156 (60.5%) and 102 (39.5%) of whom were treated with single-agent or combination therapy, respectively. We stratified patients into two groups based on baseline fT3 and fT4 values [euthyroid cohort defined by fT3 and fT4 both within the normal range vs. euthyroid sick syndrome cohort defined by low fT3 and/or fT4 levels]. We examined the differences in progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analyses. After applying propensity-score matching, we considered 88 relevant cases in each cohort. Longitudinal comparison of fT3/fT4 ratios showed a significant increase in the median value after pembrolizumab-based therapy (p < 0.001). We computed ROC curves to analyze the correlation between fT3/fT4 ratios and survival outcomes. The relative AUC values were not viable in predicting a positive outcome at the first time point. Conversely, assessment at the second time point revealed a significant association with PFS [AUC 0.82 (95% CI 0.75–0.89), p < 0.001] and OS [AUC 0.81 (95% CI 0.75–0.88), p < 0.001]. After a median follow-up of 20.2 (95% CI 16.2–24.2) months, the median PFS for the low and high fT3/fT4 ratio groups was 4.1 (95% CI 3.0–5.1) and 15.3 (95% CI 10.3–20.1) months, respectively (p < 0.001). The median OS for the low and high fT3/fT4 ratio groups was 6.7 (95% CI 4.9–8.5) and 19.6 (95% CI 16.4–22.8) months, respectively (p < 0.001). The multivariate analysis revealed that a low fT3/fT4 ratio was independently associated with shorter PFS [HR 2.51 (1.66–3.78); p < 0.001] and OS [HR 2.18 (1.43–3.34); p < 0.001]. After the optimal weighting of prognostic factors according to thyroid function impairment, the fT3/fT4 ratio at baseline did not affect the survival of patients receiving immune checkpoint blockade for advanced NSCLC. Patients with an increased fT3/fT4 ratio experienced a significantly decreased risk of disease progression and mortality. The longitudinal assessment of fT3/fT4 ratio may play a predictive role in this specific therapeutic setting. Full article

This paper describes the process of producing chemiresistors based on hybrid nanostructures obtained from graphene and conducting polymers. The technology of graphene presumed the following: dispersion and support stabilization based on the chemical vapor deposition technique; transfer of the graphene to the substrate by spin-coating of polymethyl methacrylate; and thermal treatment and electrochemical delamination. For the process at T = 950 °C, a better settlement of the grains was noticed, with the formation of layers predominantly characterized by peaks and not by depressions. The technology for obtaining hybrid nanostructures from graphene and conducting polymers was drop-casting, with solutions of Poly(3-hexylthiophene (P3HT) and Poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-bithiophene] (F8T2). In the case of F8T2, compared to P3HT, a 10 times larger dimension of grain size and about 7 times larger distances between the peak clusters were noticed. To generate chemiresistors from graphene–polymer structures, an ink-jet printer was used, and the metallization was made with commercial copper ink for printed electronics, leading to a structure of a resistor with an active surface of about 1 cm². Experimental calibration curves were plotted for both sensing structures, for a domain of CH₄ of up to 1000 ppm concentration in air. A linearity of the curve for the low concentration of CH₄ was noticed for the graphene structure with F8T2, presenting a sensitivity of about 6 times higher compared with the graphene structure with P3HT, which makes the sensing structure of graphene with F8T2 more feasible and reliable for the medical application of irritable bowel syndrome evaluation. Full article