Outcomes of Radiofrequency Ablation for Autonomously Functioning Thyroid Adenomas-Mayo Clinic Experience.

Background: Autonomously functioning thyroid nodules (AFTNs) constitute 5% to 7% of thyroid nodules and represent the second most common cause of hyperthyroidism following Graves' disease. Currently, radioactive iodine (RAI) and surgery are the standard treatment options, and both incur a risk of postprocedural hypothyroidism and other surgery and radiation-related complications. Methods: This work aimed at assessing the efficacy of radiofrequency ablation (RFA) as an alternative treatment option for resolving hyperthyroidism and the nodule volume rate reduction (VRR) and its associated adverse events. Results: A total of 22 patients underwent RFA for a solitary AFTN. Seventy-two percent (n = 16) had subclinical hyperthyroidism, 9% (n = 2) had overt hyperthyroidism, and 18% (n = 4) were biochemically euthyroid on antithyroid medication. Average pretreatment TSH was 0.41 mIU/L (SD = 0.98) and free T4 1.29 ng/dL (SD = 0.33). Following a single RFA session, hyperthyroidism resolved in 90.9% (n = 20) and average VRR (61.13%) was achieved within 3 to 6 months following the ablation. Except for 1 nodule, none of the nodules grew during the follow-up period (16.5 months). Two patients (9%) developed transient tachycardia requiring short-term beta-blocker therapy, and 2 developed mild hypothyroidism requiring levothyroxine therapy. Two patients developed recurrent hyperthyroidism and elected to undergo lobectomy and repeat RFA respectively. No serious adverse effects were noted in this cohort. Conclusion: RAI and/or surgery represent the standard of care for toxic adenomas, but RFA shows excellent efficacy and safety profile. Therefore, at centers with RFA expertise, it should be considered an alternative treatment strategy, avoiding radiation and surgery-related complications.

Genetic and clinical factors influencing CF-associated liver disease: the impact of SERPINA1 variants and CFTR genotypes in Romanian pediatric cystic fibrosis patients.

Background: Hepatic disease represents a significant complication in children with cystic fibrosis (CF), yet its relationship with specific genetic factors, including CFTR (Cystic fibrosis transmembrane conductance regulator) mutations and SERPINA1 alleles, is not well understood. This study aims to clarify these associations within a Romanian pediatric CF population. Methods: In this cross-sectional, prospective study, we examined 71 children with CF, comparing those with hepatic disease (n=25) to those without (n=46). We collected comprehensive clinical, biochemical, and genetic data, focusing on CFTR genotypes and SERPINA1 alleles. Key outcomes included the prevalence of hepatic disease in relation to specific genotypes, fibrosis markers, and liver function tests. Results: The DF508/DF508 genotype was the most prevalent, occurring in 49% of the cohort. No significant associations were found between hepatic disease and specific CFTR genotypes or SERPINA1 alleles. However, children with hepatic disease exhibited significantly higher fibrosis scores (APRI and FIB-4), suggesting more advanced liver involvement. Additionally, a slight delay in CF diagnosis was observed in those with hepatic disease, though this difference did not reach statistical significance. Conclusion: This pioneering study in Romania underscores the complexity of hepatic disease in CF. While specific CFTR genotypes and SERPINA1 alleles were not significantly associated with hepatic complications, the findings emphasize the importance of early diagnosis and monitoring using fibrosis markers to identify children at risk for liver involvement.

The development of an augmented reality application for exercise prescription within paediatric oncology: App design and protocol of a pilot study.

Background: Children and young people with cancer face barriers when engaging with exercise, such as treatment-related side effects, psychosocial burdens and lack of individualised provisions. Digital health tools, such as smartphone applications, have emerged as a promising driver to support healthcare provisions in exercise prescription among patients. It is vital to explore how such technologies can be developed more effectively in order to strengthen the evidence supporting their use and for more appropriate implementation within healthcare. This study aims to explore user experiences, preferences and suggested improvements from healthy children and young people aged 9-21 years. Methods: An augmented reality (AR) application was specifically developed for children and young people aged 9-21 years undergoing cancer treatment and a protocol for a pilot study was designed. The target sample of this pilot study is 90 healthy children and young people aged 9-21 years. Practical 30-min workshops will be conducted encouraging participants to engage with the smartphone app. Focus groups will explore participant experiences, preferences, and suggested improvements. Data will be analysed deductively with apriori themes derived from the semi-structured interviews. Discussion: Obtaining user experiences, preferences and suggested improvements is especially important for the development of novel apps, such as those prescribing exercise and using algorithms and augmented reality software. Results from this study will directly influence the development of an augmented reality application, which will also be applied within a long-term trial in paediatric oncology.

The added value of cultured cells in burn treatment: A systematic review.

INTRODUCTION: Advancements in resuscitative care and burn surgery have improved survival rates after extensive burn injuries, shifting focus to enhancing the quality of survival. Conventional treatment with split-thickness skin grafts (STSG) presents limitations such as donor-site morbidity, limited availability in extensive burn injuries, and hypertrophic scarring. Tissue engineering aims to address these drawbacks by developing optimal skin substitutes. This systematic review aims to provide an overview of the current applications of cultured cells in burn surgery, encompassing diverse approaches and addressing existing challenges to enhance burn wound management and improve patient outcomes. METHODS: Following PRISMA guidelines, a comprehensive search was performed across three databases (PubMed, Embase, Cochrane Library) for articles on cultured cell use in burn treatment. Only clinical studies were included. Articles were screened by two independent reviewers. Quality assessment was performed. RESULTS: The search yielded 167 articles, of which 14 met the eligibility criteria. The selection included 8 randomized controlled trials, 5 prospective cohort trials, and 1 retrospective cohort study. Various tissue-engineered skin substitutes, from cultured epidermal autografts to dermal regeneration templates seeded with cultured cells, showed promising outcomes. Several substitutes exhibited take rates comparable to STSG with improved scar quality. CONCLUSION: Results are promising, though standardization of cultured skin substitutes and robust clinical trials with larger populations and appropriate comparators are still lacking.

Staged Phalloplasty by Metoidioplasty First Does Not Appear to Lower Complication Rates.

Purpose: Genital gender-affirming surgery in transmasculine patients encompasses both metoidioplasty and phalloplasty. Some patients opt to undergo staged phalloplasty by metoidioplasty first (SPMF). The aim of this study was to evaluate whether SPMF is associated with less surgical complications compared with immediate phalloplasty (IP). Methods: Our institutional database was retrospectively evaluated to identify transmasculine patients who underwent SPMF between 2006 and 2020. These patients were matched based on the type of flap (radial forearm free flap vs. anterolateral thigh flap) and for the time period in regard to patients who underwent IP. Both groups were compared on patient characteristics, perioperative and postoperative outcomes. Results: Twenty-seven patients with SPMF were matched with 27 IP patients. Median follow-up after phalloplasty was held, respectively, 32 and 33 months after the intervention for SPMF and IP (p=0.99). There were no significant differences in age, body mass index, and smoking habits between both groups. For SPMF, metoidioplasty required subsequent corrective surgery before phalloplasty in three patients (11%). For SPMF and IP, median operation time was 396 and 410 min (p=0.6), median hospital stay was 16 and 17 days (p=0.5), and median catheter stay was 19 and 20 days (p=0.9). In both groups, 16 patients (59%) needed at least one additional surgical procedure for postoperative complications, urethral complications (stricture, fistula), and/or flap-related complications. Conclusion: In our cohort, complications were not reduced by SPMF. In case metoidioplasty is considered as a step toward phalloplasty, separate morbidity of metoidioplasty must be taken into account.

Immediate results of transcatheter aortic valve implantation.

OBJECTIVE: Aim: To assess, analyze and present early postoperative results of transcatheter aortic valve implantation in patients with aortic stenosis. PATIENTS AND METHODS: Materials and Methods: During the period from 2017 to 2023, we examined in total 77 patients with severe aortic stenosis and high risk of surgery who were eligible for the TAVI procedure at the "Heart Institute Ministry of Health of Ukraine". RESULTS: Results: Before implantation, the mean and maximum aortic valve gradients were 53.7±19.1 mm Hg and 90.1±28.8 mm Hg, respectively. The mean and maximum aortic valve gradients after implantation were 9.67±3.18 and 18.7±6.41, respectively (p<0.001). The calculated left ventricular ejection fraction was 57.5±8.22% before surgery and 58.8±7.91% after surgery (p=0.412). After the procedure, moderate (2) degree of paravalvular aortic regurgitation was observed in 2 patients and light degree - in 21 patients. Before surgery, mitral regurgitation of 2-3 degrees was observed in 15 patients, and only in two patients after TAVI The survival rate of our patients was 96.4% after 180 days of supervision. In-hospital and 30-day mortality was 1.8%, while 180-day mortality was 3.6%. No deterioration was observed in patients with moderate aortic regurgitation during echocardiographic studies performed at 1, 3 and 6 months after TAVI. CONCLUSION: Conclusions: TAVI is rapidly emerging as a life-saving alternative for patients who are inoperable or at high risk of surgery due to comorbidities. The selection of patients for TAVI is important to optimize procedural and long-term outcomes. It is important for cardiologists in our country to refer patients with severe aortic stenosis after diagnosis to centers that perform TAVI.

Use of the superficial circumflex iliac artery perforator flap for urethra and/or shaft reconstruction in gender diverse persons: 10-year single center experience.

BACKGROUND: Although the free radial forearm flap (FRFF) is the gold standard for phalloplasty, the conspicuous donor-site scar, need for microsurgery and the tendency for the phallus to deflate over time makes both patients and surgeons look for alternatives. We describe our long-term experience with the pedicled superficial circumflex iliac artery (SCIP) flap for urethral and/or penile shaft reconstruction. This flap can be applied for similar indications as FRFF-phalloplasty, but with primary closure of the donor site(s) and without microsurgery. METHODS: We retrospectively reviewed surgical outcomes of all patients who underwent urethra and/or shaft reconstruction using SCIP-flaps as part of phalloplasty for gender-affirming surgery in our center between 2012 and 2022. RESULTS: Over a 10-year period, 55 SCIP-flaps were performed as part of phalloplasty. This included 47 unilateral SCIP-flaps, of which 10 were used for shaft reconstructions and 37 for urethra reconstructions. Primary closure was achieved in 100% of patients. No failures were observed for shaft reconstructions.For urethra reconstructions, 8 SCIP-urethras (14%) failed completely, and 3 SCIP-flaps were converted to free flaps. In total, 82% of patients with a SCIP-urethra reconstruction were able to stand while voiding.Eight bilateral SCIP-flaps were performed for one-stage shaft and urethra creation, of which 3 patients (38%) experienced urethral fistulas and/or strictures. CONCLUSIONS: This study shows that the SCIP-flap is a technically feasible and safe pedicled alternative for urethral and penile shaft reconstruction in gender diverse individuals, with similar urethral complication rates compared to FRFF and ALT-phalloplasty, however, with potentially lower shaft sensation.

AGO2 protein: a key enzyme in the miRNA pathway as a novel biomarker in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy characterised by diagnostic challenges, high recurrence rates, and poor prognosis. This study explored the role microRNA (miRNA) processing genes in ACC, and their potential role as diagnostic and prognostic biomarkers. We analysed the mRNA expression levels of miRNA machinery components (DROSHA, DGCR8, XPO5, RAN, DICER, TARBP2 and AGO2) utilising mRNA-Seq data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) projects. Additionally, protein levels were quantified in tissue samples from the Kolling Institute of Medical Research's tumour bank. Our results demonstrated that among all miRNA processing components, AGO2 exhibited significant overexpression in ACC compared to the normal adrenal cortex (NAC) and benign adrenal adenoma (AA) (p < 0.001). Kaplan-Meier survival analysis indicated that higher AGO2 expression correlated with significantly worse overall survival in ACC patients (HR 7.07, p < 0.001). Among 32 cancer types in TCGA, the prognostic significance of AGO2 was most prominent in ACC. This study is the first to report AGO2's potential as a diagnostic and prognostic biomarker in ACC, emphasising its significance in ACC pathogenesis and potential application as a non-invasive liquid biopsy biomarker.

Degranulation assay to evaluate NK cell natural and antibody-dependent cell-mediated cytotoxicity against A549 tumor spheroids.

Adoptive natural killer (NK) cell-based immunotherapy is a promising treatment approach in cancer that is showing notable efficacy against hematological malignancies. However, the success of NK cell immunotherapy in patients with solid tumors is limited due to several barriers, which include the immunosuppressive tumor microenvironment (TME), heterogeneity of tumor cells and poor NK cell infiltration into the tumor. Advances in 3D in vitro culture technologies have opened new avenues for the development of more physiological human cancer models that mimic important tumor features which are absent in traditional 2D studies and may be essential for the improvement of immunotherapies against solid tumors. Here, we describe a comprehensive protocol to generate tumor spheroids from the A549 lung carcinoma cell line, then establish co-cultures with NK cells to, ultimately, determine NK cell functional response with a degranulation assay, a surrogate of NK cell cytotoxicity against tumor spheroids. Additionally, we studied degranulation by stimulating NK cell antibody-dependent cell-mediated cytotoxicity (ADCC) with cetuximab, an IgG1 monoclonal antibody used in cancer therapy. Likewise, other monoclonal antibodies or combination treatments could also be studied in this 3D co-culture system, providing very valuable information to define effective combinations of therapeutic agents able to generate NK cells with high cytotoxic potential that could lead to more successful adoptive NK cell-based therapies for the treatment of solid tumors.

Multispectral Imaging of Collagen, NAD(P)H and Flavin Autofluorescence in Mesenchymal Stem Cells Undergoing Trilineage Differentiation.

Understanding the molecular mechanisms of differentiation is important for regenerative medicine and developmental biology. This study aims to characterise the role of the glycolysis/oxidative phosphorylation balance as a driver of mesenchymal stem cell (MSC) differentiation. Cells were maintained in normal conditions or stimulated towards the MSC trilineage cell types over 21 days. Multispectral imaging of cell autofluorescence was applied as a non-invasive methodology to continuously image cultures in situ. Spectral signals for collagen, NAD(P)H, and flavins were unmixed. MSCs cultured under chondrogenic conditions exhibited increased collagen levels relative to controls. Following osteogenic induction, MSCs showed increased collagen levels relative to controls during the earlier stages of culture; however, control cells increased their collagen levels as they became confluent. MSCs cultured under adipogenic conditions exhibited lower levels of collagen than controls. The redox ratio (RR; NAD(P)H/flavins) immediately decreased during chondrogenesis, with this early effect persisting throughout the culture compared to control cells, which appeared to increase their RR, similar to osteogenesis. Adipogenesis resulted in a small increase in RR on day 2 relative to control cells, followed by a persistent decrease. Chondrogenic and adipogenic differentiation favoured oxidative phosphorylation, whereas osteogenesis and MSC overgrowth resulted in a glycolytic metabolism. Following consideration of these findings, as well as the diverse reports in the literature, it is concluded that neither enhanced oxidative phosphorylation nor glycolysis are fundamental to the canonical modes of differentiation, and researchers should avoid interpreting shifts as indicating differentiation.

Biochemical assessment in a cohort of pediatric patients with cystic fibrosis.

Cystic fibrosis (CF) is a recessive inherited disorder caused by genetic mutations in the CF transmembrane conductance regulator (CFTR) gene. It is a multisystem condition that primarily induces abnormal mucus accumulation in the respiratory system and obstructs the intrapancreatic common bile duct, causing a reduction in the delivery of digestive enzymes to the small intestine. Thus, patients with CF are characterized by maldigestion, malabsorption, and recurrent airway bacterial infections. Clinical monitoring of the health status of patients with CF is mandatory for increasing the patients' lifespan. To assess the feasibility of monitoring life quality (LQ) in pediatric patients with cystic fibrosis (CF) and to explore the relationship between biochemical parameters and clinical symptoms, our study analyzed inflammatory responses related to CF, medication, and pulmonary bacterial infections in 52 patients diagnosed with CF. Blood, hypo-pharyngeal exudate, and fecal samples were analyzed using clinical biochemistry, hematology, and microbiology techniques at the Alessandrescu-Rusescu National Institute for Mother and Child Health central laboratory in Bucharest, Romania. All the participants adhered to their prescribed outpatient CF regimens and appeared clinically stable. The overall clinical status of patients with CF was observed and compared with that of a healthy control group, which consisted of individuals similar in number and age. The screened patients with CF presented an impaired lipid status and chronic infections with various bacteria, iron, and vitamin (A, D, and E) deficiencies. Our findings provide insights into the pathophysiological mechanisms of CF and suggest that tailored monitoring and personalized therapeutic strategies could improve patient management.

Impact of CFTR Modulator Therapies on Liver Function in Cystic Fibrosis Patients: A Systematic Review of Hepatic Biomarkers.

BACKGROUND AND AIMS: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor/ivacaftor/tezacaftor (ETI) and lumacaftor/ivacaftor (LI), have revolutionized the treatment of cystic fibrosis. However, their impact on liver function remains unclear, with varying effects reported across studies. The aim of this study was to systematically review the effects of CFTR modulators on liver function in cystic fibrosis patients by evaluating changes in key hepatic biomarkers. METHODS: A comprehensive literature search was conducted in Europe PubMed Central and PubMed databases for studies published between January 1, 2010, and December 31, 2023. Eligible studies included those assessing the impact of CFTR modulators on liver biomarkers in cystic fibrosis patients. Meta-analyses were performed where possible. RESULTS: Six studies encompassing 195 patients were included, with significant heterogeneity in study design, population, and outcomes. The review found mixed results for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyltransferase (GGT) levels, with some studies reporting increases and others decreases. LI therapy was associated with significant reductions in GGT and alkaline phosphatase (AP) levels, while ETI therapy showed significant increases in bilirubin levels. Albumin levels increased significantly with both therapies. CONCLUSIONS: CFTR modulators have varying effects on liver function biomarkers in cystic fibrosis patients, with LI therapy generally showing more favorable outcomes on liver health. The significant heterogeneity among studies underscores the need for more standardized research to better understand these effects and guide clinical management.

Adipocyte maturation impacts daunorubicin disposition and metabolism.

INTRODUCTION: Acute lymphoblastic leukaemia (ALL) is the most common type of childhood leukaemia with effective chemotherapeutic treatment. However, obesity has been associated with higher ALL chemoresistance rates and lower event-free survival rates. The molecular mechanism of how obesity promotes chemotherapy resistance is not well delineated. OBJECTIVES: This study evaluated the effect of adipocyte maturation on sequestration and metabolism of chemotherapeutic drug daunorubicin (DNR). METHODS: Using targeted LC-MS/MS multi-analyte assay, DNR sequestration and metabolism were studied in human preadipocyte and adipocyte cell lines, where expressions of DNR-metabolizing enzymes aldo-keto reductases (AKR) and carbonyl reductases (CBR) were also evaluated. In addition, to identify the most DNR-metabolizing AKR/CBR isoforms, recombinant human AKR and CBR enzymes were subject to DNR metabolism. The results were further validated by AKR-, CBR-specific inhibitors. RESULTS: This report shows that adipocyte maturation upregulates expressions of AKR and CBR enzymes (by 4- to 60- folds, p < .05), which is positively associated with enhanced sequestration and metabolism of DNR in adipocytes compared to preadipocytes (by ~30%, p < .05). In particular, adipocyte maturation upregulates AKR1C3 and CBR1, which are the predominate metabolic enzyme isoforms responsible for DNR biotransformation to its metabolites. CONCLUSION: Fat is an expandable tissue that can sequester and detoxify DNR when stimulated by obesity, likely through the upregulation of DNR-metabolizing enzymes AKR1C3 and CBR1. Our data partially explains why obese ALL patients may be more likely to become chemoresistant towards DNR, and provides evidence for potential clinical investigation targeting obesity to reduce DNR chemoresistance.

KECORT Study: An International e-Delphi Study on the Treatment of KEloids Using Intralesional CORTicosteroids in Clinical Practice.

BACKGROUND: Intralesional corticosteroid administration (ICA) is a first-line keloid treatment. However, it faces significant variability in current clinical and scientific practice, which hinders comparability of treatment results. OBJECTIVES: The aim of the study was to reach consensus on different aspects of ICA using hypodermic needles in keloids among an international group of dermatologists and plastic surgeons specialized in keloid treatment to provide consensus-based clinical treatment recommendations for all physicians treating keloids. METHODS: The keloid expert panel of 12 dermatologists and 11 plastic surgeons rated 30 statements. Two online e-Delphi rounds were held, both with a response rate of 100%. Fifteen (65%) keloid experts participated in the final consensus meetings. Consensus was defined as ≥ 75% of the participants choosing agree or strongly agree on a 7-point Likert scale. RESULTS: Consensus was reached on treatment goals, indication for ICA, triamcinolone acetonide (TAC) 40 mg/mL as the preferred corticosteroid administered at a maximum of 80 mg per month and at intervals of 4 weeks, minimizing pain during ICA, the use of 1 mL syringes and 25 or 27 Gauge needles, blanching as endpoint of successful infiltration, caution of not injecting subcutaneously, and the option of making multiple passes in very firm keloids prior to infiltration. Consensus could not be reached on TAC dosing, methods of prior local anesthesia, and location of injection. CONCLUSIONS: This e-Delphi study provides important clinical treatment recommendations on essential aspects of ICA in keloids. By implementing these recommendations, uniformity of ICA in keloid treatment will increase and better treatment results may be achieved.

A Potential Role for Nivolumab in the Treatment of Fibrous Dysplasia-Related Pain.

Fibrous dysplasia (FD) is a chronic and progressive disorder of bone growth because of decreased osteoblast formation and osteoclast overactivity. Its main symptoms include pain, fracture, and irregular bone growth. Bisphosphonates are the mainstay of therapy for FD with a primary goal of pain relief. A 50-year-old woman presented to ophthalmology in March 2011 with intermittent proptosis, vertical diplopia, and orbital pain. A computed tomography scan of the head revealed a skull base lesion, which was confirmed to be fibrous dysplasia on bone biopsy. Because of significant headache, she was treated with IV pamidronate monthly starting November 2011, which led to pain reduction. Repeated attempts to decrease the frequency of pamidronate were unsuccessful because of breakthrough pain. Oral alendronate and risedronate did not control her symptoms. She remained on risedronate however because of its convenience. In August 2021, she was diagnosed with metastatic melanoma and started nivolumab. Her headache completely resolved for the first time in 10 years. Although nivolumab, a programmed death-1 blocker, has been used in the treatment of bone malignancy, it has not been previously studied in FD. By suppressing RANK ligand-related osteoclastogenesis, nivolumab decreases cancer-associated bone pain. Our case suggests a potential role for nivolumab in treating FD-associated pain.

Measuring Oxygen Solubility in Amorphous and Semicrystalline Polyolefins Using Test Particle Insertion: A Comparative Study of Polyethylene and Isotactic Polypropylene.

The test particle insertion method is used to study the solubility of oxygen in two commonly used polymers: polyethylene (PE) and isotactic polypropylene (iPP). Amorphous samples for both polymers were prepared by means of Monte Carlo and molecular dynamics simulations, and the oxygen solubility was measured across different temperatures. The solubility-temperature dependence for iPP proved to be nonmonotonic due to the interplay between binding and reorganizational enthalpy, while for PE, it appeared to be monotonic based on the available data in the studied temperature range. A broad comparison to experiments and simulations is included. Further oxygen insertions were also performed in semicrystalline PE and iPP samples at ambient temperature, and the obtained values were compared to a linear relationship which correlates the solubility in the purely amorphous phase with the solubility in the crystalline phase. The solubility of PE closely follows the linear relationship, while iPP exhibits some divergence. All the semicrystalline samples were previously annealed at elevated temperatures for long periods (a few µs), and a strong effect of annealing was observed on the structure and the solubility of iPP. A well-developed iPP lamellar structure emerged at longer annealing times, while PE develops that structure already in the early crystallization stages. The solubility of semicrystalline iPP samples with lamellar morphology exhibited better agreement with extrapolated solubility values of the amorphous state─the extrapolation was made using a linear relationship connecting solubility in the purely amorphous phase and solubility in mixed phases (amorphous and crystalline). Results on the correlation of the solubility with the local structural ordering are also present.

Comparative evaluation of plasma biomarkers of Schistosoma haematobium infection in endemic populations from Burkina Faso.

Infection with Schistosoma haematobium causes urogenital disease associated with organ disfunction, bleeding, pain, and higher susceptibility to infections and cancer. Timely and accurate diagnosis is crucial for prompt and appropriate treatment as well as surveillance efforts, and the use of plasma biomarkers offers important advantages over parasitological examination of urine, including increased sensitivity and the possibility to use the same specimen for multiple investigations. The present study aims to evaluate the diagnostic performance of different plasma biomarkers in endemic populations from Burkina Faso, West Africa. Schistosoma spp. Circulating Anodic Antigen (CAA), cell free S. haematobium DNA (cfDNA), class M and G antibodies against S. haematobium Soluble Worm Antigen Preparation (SWAP) and Soluble Egg Antigen (SEA) were measured in 406 plasma samples. Results of each biomarker test were compared to those of CAA, a Composite Reference Standard (CRS) and Latent Class Analysis (LCA). An identical proportion of positive samples (29%) was observed as a result of CAA and cfDNA testing, with a substantial agreement (84%, Cohen k = 0.62) between the results of the two tests, and a comparable agreement with the results of CRS and LCA. A higher positivity was observed, as expected, as a result of specific antibody testing (47%-72%), with IgG showing a higher agreement than IgM with the three references. Also, higher IgG levels were observed in current vs past infection, and ROC analysis identified optimal cutoff values for improved testing accuracy. This study provides compelling evidence that can inform the choice of the most appropriate diagnostic plasma biomarker for urogenital schistosomiasis in endemic areas, depending on the purpose, context, and available resources for testing. Either CAA or cfDNA testing can be used for the diagnosis of patients and for epidemiological investigations, even in absence of urine filtration microscopy, whereas anti-SWAP or anti-SEA IgG can be employed for surveillance and integrated monitoring of control interventions against poverty-associated diseases.

Reducing noise in radioactive iodine activity selection: the utility of an online clinical calculator.

Background: Noise, an unwanted variability in judgment, is ubiquitous in medicine, including in the prescription of radioactive iodine (RAI). Building upon our recently developed predictive risk model, we created an online clinical support tool to facilitate the translation of our model into clinical practice. The aim of this study is to assess the utility of an online clinical support tool to reduce noise in the treatment for patients with differentiated thyroid cancer (DTC). Methods: The tool was accessible via weblink or a QR code. Activity recommendations were applied to the calculator's four risk categories: 0 GBq for very low risk, 1 GBq for low risk, 4 GBq for intermediate risk, and 6 GBq for high risk. The tool was applied prospectively to 103 patients who received RAI at Royal North Shore Hospital between 2021 and 2022 and retrospectively to 393 patients treated with RAI between 2017 and 2021. Results: A significant difference was observed in administered activity between the 2021-2022 and 2017-2021 cohorts in patients stratified as intermediate risk (median activity 3.95 GBq, interquartile range 2.03-4.04 vs 4 GBq, 4-4) and high risk (4.07 GBq, 3.95-5.7 vs 6 GBq, 6-6) with P-values of 0.01 and <0.01, respectively. No difference was seen in low-risk patients (2.01 GBq, 1.03-3.98 vs 1 GBq, 1-4, P = 0.30). Additionally, no clinically significant recurrence was observed between the two cohorts (6.6% vs 4.5%; P = 0.628). Conclusion: Optimal risk classification and activity recommendation continue to be established. Our data suggest that providing risk stratification and activity recommendation in an easy-to-access online tool can reduce noise and variability in activity prescription for patients with DTC.