BackgroundLate-onset Pompe’s disease (LOPD) is a progressive treatable metabolic myopathy due to partial acid α-glucosidase (GAA) deficiency, with potential onset during the pediatric age. To date, Pompe’s disease is not widely included in newborn screening panels, so that clinical suspect remains essential for timely diagnosis and management. Clinical identification of LOPD was shown to be challenging in adult patients, whereas data in children and adolescents are scanty. We conducted an Italian nationwide multicentric survey in order to delineate the characteristics of LOPD in the pediatric population. This prompted us to propose a diagnostic algorithm to facilitate the identification of LOPD in pediatrics.ResultsThe survey provided information on 38 Italian pediatric patients with a definite biochemical and molecular diagnosis of LOPD firstly suspected based on clinical approach. Nineteen patients (50%) reached medical attention because of clinical symptoms of LOPD (79% within 3 years of age; 21% at 3–18 years of age) and 19 (50%) because of incidental finding of asymptomatic hyperCKemia. All the 38 LOPD patients showed hyperCKemia (56%: range 500–1000 U/l; 18%; range 250–500 U/l; 18% range 1000–2000 U/l; 8% >2000 U/l), almost invariably accompained by concomitant hypertransaminasemia (91%). Main clinical symptoms before 3 years of age were inability to (1) sit at 8 months, (2) walk indipendently at 18 months, and (3) climb stairs at 30 months. Later pediatric presentations (3–18 years of age) were limitation to (1) get up from supine position, (2) perform sport activity, and (3) run. In symptomatic patients, diagnostic latency (i.e. the time interval between clinical onset and diagnosis of LOPD) ranged from < 1 year (58%) to 2–12 years (42%).ConclusionsClinical diagnosis of LOPD in pediatrics is challenging in spite of its frequent presentation within 3 years of age. A selective screening by measuring GAA activity on dried blood spot in the two main clinical diagnostic contexts of LOPD in pediatrics – namely (1) age-related myopathic symptoms or (2) asymptomatic hyperCKemia (and hypertransaminasemia) – will likely ensure diagnostic anticipation for those patients not screened for Pompe’s disease in the neonatal period.

New cortisol assay-specific thresholds for the biochemical diagnosis of adrenal insufficiency after ACTH stimulation

Dual-functional nitrogen-doped carbon quantum dots: Highly selective and smartphone detection of lactic acid/L-arginine, mechanisms and applications.

Disclosure: D. Dash: None. D. Ayyagari: None. D. Puran: None. D. Pandey: None.IntroductionVan WYK- Grumbach Syndrome (VWGS) is a rare syndrome in pre-pubertal girls associated with long standing untreated hypothyroidism, cause stimulation of FSH receptors leading to bilateral enlarged multi-cystic ovaries, iso-sexual precocious pseudo-puberty, and delayed bone age. Case presentationWe report a case of 4 year 8 month old girl presenting with bleeding per vagina (PV) for 10 days, enlargement of both breasts for past 2 months. Physical examination revealed significant short stature (height < 5th centile CDC), with breast enlargement tanner stage 3 without axillary or pubic hair. She was anemic with coarse facial features (thick lips, protruded tongue) and protruded abdomen. Bone age was 3 years(Greulich pyle). There was no pericardial effusion, galactorrhoea, hirsutism or cafe au lait spots. Investigation revealed biochemical evidence of primary hypothyroidism (TSH>100IU/ml) with pre-pubertal gonadotropins and estrogen. Anti-TPO antibody was positive. Ultrasonography of abdomen showed bilateral multicystic ovaries. She was treated with thyroxine replacement therapy. At 3 month follow-up visit, she was clinically & biochemically euthyroid, had no further per vaginal bleeding, and breast size reduced to Tanner Stage 2. Abdominal protrusion and coarse features had resolved. Discussion: VWGS is one of the syndromes of GnRH-independent sexual precocity, presenting with per vaginal bleeding and breast enlargement, but no pubic hair in girls and macroorchidism in boys. Stimulation of the gonadal FSH receptor by TSH leads to a FSH/oestrogen dominant clinical syndrome with breast development, follicular cysts, and menstruation presenting the predominant clinical features of pseudo-precocious puberty. The severity of the TSH elevation may be proportionate to the severity sexual precocity, with reversal of clinical features and pathology to a pre-pubertal state following thyroid hormone replacement. Conclusion: Precocious puberty needs meticulous history, clinical examination and biochemical diagnosis. The presence of enlarged ovaries and precocious puberty may suggest an estrogen secreting ovarian tumour. However, pre-pubetal gonadotrophin and estogen levels should raise the suspicion of VWGS. VWGS presents a rare but treatable cause of precocious puberty, which, with timely diagnosis, and initiation of an inexpensive drug, thyroxine, will allow us to avoid unnecessary and expensive investigations and interventions.Presentation: Saturday, July 12, 2025

Disclosure: G.J. Acosta: None. R.E. Medina: None. M. Kabbash: None. P.T. Dziegielewski: None. C.M. Shaw: None. A.S. Shirali: None.Introduction: Older adults experience declining rates of parathyroidectomy despite meeting indications for surgery based on management guidelines for primary hyperparathyroidism. We sought to examine age-specific differences in the diagnosis of primary hyperparathyroidism (PHPT), time to surgery, and indications for surgery in patients who were offered parathyroidectomy. Methods: Adult patients with sporadic PHPT who underwent parathyroidectomy at a single tertiary academic medical center between 1/1/2017 and 12/31/2022 were identified. The 2016 American Association of Endocrine Surgeons (AAES) Guidelines and the Fourth International Workshop Guidelines for definitive management of PHPT were used to identify evidence-based indications for surgery. The number of patients with a complete preoperative evaluation, defined as pre-op corrected serum calcium, PTH, 25-hydroxy vitamin D, eGFR, DXA scan or bone imaging, and 24-hour urine calcium, was calculated. Results: Two hundred sixty-six patients (median age 63.2 years, 74.8% female) underwent parathyroidectomy for PHPT. From the total 266 patients, 145 patients (54.5%) were <65 years (median age 54.9 years) and 121 patients (45.5%) were ≥65 years (median age 71.4 years). There was no significant difference in the interval of time from initial calcium elevation to first PTH testing between the two groups. The median time from biochemical diagnosis to surgery was significantly shorter for patients <65 years (7.53 months vs 14.5 months, p<0.05). Patients ≥65 years were more likely to undergo parathyroidectomy due to bone disease (31.4 vs 20.0%, p<0.05). Patients ≥65 years who underwent parathyroidectomy were less likely to have nephrolithiasis (29.8% vs 43.3%, p<0.05) and more likely to have eGFR <60 (43.8% vs 13.1%, p<0.001). Only 86 patients (32.3%) underwent complete preoperative evaluation for PHPT prior to being offered parathyroidectomy, with no difference between those <65 years and those ≥65 years (31.7% vs 32.2%, respectively, p>0.005). Conclusions: Older adults undergo parathyroidectomy twice as long after the initial biochemical diagnosis compared to patients <65 years despite having similarly low rates of complete preoperative evaluation. Older adults were more likely to undergo surgery for bone disease and renal dysfunction. Older adult patients may benefit from more comprehensive evaluations and earlier referral to surgery to mitigate negative skeletal, renal and cardiovascular outcomes.Presentation: Saturday, July 12, 2025

Disclosure: E. Wang: None. G.E. Vates: None. I. Shafiq: None.Background: Thyrotropin-secreting pituitary adenomas (TSHomas) are rare, accounting for less than 1% of all pituitary adenomas causing hyperthyroidism. Misdiagnosis with primary thyroid disorders often delays accurate diagnosis and management. This study aims to expand diagnostic, prognostic, and therapeutic data on TSHomas to improve care for future patients. Methods: A retrospective analysis was performed in patients with clinical and biochemical diagnosis of TSHomas at the University of Rochester Pituitary Program between 2006 and 2024. Patient’s demographics, laboratory findings, medical history, imaging results and treatment details and treatment were collected and analyzed. Results: Six patients, with an average age of 50.5 years at diagnosis, were identified. Of these, 67% of the patients were female and the mean duration of symptoms before diagnosis was 3.7 years. 67% of patients were previously diagnosed with hypothyroidism and 50% were treated with levothyroxine. The most common presenting symptoms were cardiac abnormalities (83%), including palpitation (50%). Additional symptoms include thermal instability (50%), anxiety (33%) and tremors (33%). Goiter/thyroid nodules was found in 33% of patients. At diagnosis, the average TSH level was 5.8uIU/ml (normal range 0.27-4.20uIU/ml), the average free T4 level was 2.7 ng/dL (normal range 0.9-1.7 ng/dL), and the average free T3 level (measured in three patients) was 8.3pg/ml (normal range 2-4.4 pg/ml). Alpha subunit levels were assessed in four patients and was reported normal in three. All patients were identified to have macroadenoma on MRI, with tumor sizes ranging between 14mm to 27 mm (mean:19mm). Transsphenoidal surgical resection was performed in 83% of patients, and 17% were treated only with somatostatin analogues. One patient was treated with radiation and thyroidectomy after transsphenoidal surgery. Post-treatment TSH levels normalized in 83% of patients. Conclusion: TSHomas are exceedingly rare, with only six cases identified over the past two decades at our Pituitary Program. Misdiagnosis with primary thyroid disorder contributes to significant diagnostic delay. Cardiac abnormalities were the most common symptom at presentation. Despite these challenges, surgical and medical management in a multidisciplinary setting yielded favorable outcomes, with most patients achieving normalization of TSH levels.Presentation: Monday, July 14, 2025

Abstract Disclosure: G. Saha: Employee and shareholder of Rezolute Inc. E. O'Boyle: Employee and shareholder of Rezolute Inc. L. Lugos: Employee and shareholder of Rezolute Inc. J.K. Sidhu: Employee and shareholder of Rezolute Inc. D.E. Hood: Employee and shareholder of Rezolute Inc. B.K. Roberts: Employee and shareholder of Rezolute Inc. Background: Congenital hyperinsulinism (cHI) is a rare, primarily pediatric condition characterized by recurrent, persistent hypoketotic hypoglycemia due to dysregulated insulin secretion, placing those with the condition at risk for seizures, lifelong neurologic impairment, and death if not recognized and adequately treated in timely fashion. Even with vigilant glucose monitoring alongside intensive medical/feeding regimens, approximately one third of patients/caregivers report recurrent hypoglycemia events (&amp;lt;70mg/dL) daily to several times per week, and neurologic sequalae are common in spite of burdensome management efforts. Ersodetug is a fully human IgG2 monoclonal antibody that allosterically and reversibly binds the insulin receptor, thereby decreasing excessive insulin action in target tissue. A previous Phase 2 study (RIZE) demonstrated that ersodetug was generally safe and well tolerated and resulted in significant reductions in hypoglycemia events and duration. A pivotal, randomized, controlled Phase 3 study with ersodetug (RZ358-301; sunRIZE) is currently ongoing. Objective: Describe the demographic and baseline characteristics of the enrolled sunRIZE study population to inform understanding of disease burden and the extent of persistent hypoglycemia events and time in eligible patients, which are the primary and key secondary study endpoints, respectively, by which the therapeutic response to ersodetug will be evaluated at study completion. Study Design: sunRIZE is a global Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-arm, efficacy, and safety study of ersodetug in participants with a known clinical and biochemical diagnosis of cHI with inadequate hypoglycemia control on available standard of care (SoC) therapies. Eligible patients are required to have ≥3 hypoglycemic events per week by self-monitored blood glucose and spend ≥8% of time in hypoglycemia by continuous glucometer. The study is intended to enroll approximately 56 participants, including approximately 48 participants (≥3 months to ≤45 years of age) in randomized, double-blind, placebo-controlled arms of either 5 or 10 mg/kg ersodetug or placebo, administered bi-weekly during a loading phase, followed by maintenance administration every four weeks, as add on to SoC. The initial eight infants (≥3 months to &amp;lt;1 year of age) received ersodetug in open-label fashion, before subsequently being eligible to participate in the controlled study arms. The pivotal portion of the study is 24 weeks, followed by a roll-over of patients into open-label extension. Results: The trial is in progress with enrollment nearing completion. Preliminary patient demographics and baseline characteristics from at least 56 enrolled participants from the pooled treatment groups will be available for Congress presentation, using summary (descriptive) statistics. Presentation: Monday, July 14, 2025

Background: Haemoglobinopathies are among the most common monogenic disorders worldwide. Early identification of asymptomatic carriers through reliable screening and molecular diagnostics is crucial for prevention programmes, especially in high-prevalence regions such as Southern Italy. Methods: A total of 5243 individuals were analysed between 2013 and 2024 using both biochemical and genetic parameters. First-level screening included full blood count, iron status, and high-performance liquid chromatography (HPLC) for haemoglobin variant quantification. Molecular analyses were performed using next-generation sequencing (NGS) for the HBA1, HBA2, and HBB genes. Results: We identified 267 individuals (11.2%) as carriers of α-thalassaemia and 473 individuals (16.7%) as carriers of β-thalassaemia. Among them, 5 were compound heterozygotes and 3 homozygous for the α-3.7 deletion. A rare case of HbG Philadelphia in association with a triplicated α-gene was also observed. The most common β-globin mutations included c.118C&gt;T (β039, 44%), IVS-I-110 (17.7%), IVS-I-6 (12.7%), and IVS-I-1 (12.3%). Among α-globin mutations, the most prevalent were -α3.7 (48%), α2 IVS1 -5nt (15.4%), -20.5 Kb (14.2%), and triplicated α (11%). In total, 18.7% of individuals were found to carry either α- or β-thalassaemia traits. Conclusion: Our findings highlight the limitations of traditional diagnostic methods—such as the osmotic fragility test—and the importance of integrating haematological, biochemical, and molecular data to accurately identify thalassaemia carriers. The variability of genotype–phenotype correlations, especially in the context of immigration and genetic diversity, underscores the need for comprehensive molecular analysis. We propose a three-step diagnostic algorithm combining first-level screening, iron status assessment, and NGS-based sequencing for inconclusive cases.

Background: The aim of this study was to evaluate the changes in platelet indices (PLT) provided by the ADVIA 2120 hematology analyzer (Siemens Hematology System) in the early stages of onset of infections and acute coronary syndromes (ACSs). Methods: Samples were selected from 40 patients admitted to the intensive care unit with suspected uncomplicated sepsis at presentation, from 40 patients with a biochemical diagnosis of ACS at presentation and from 40 apparently healthy subjects. These samples were tested for PLT and PLT indices [mean platelet volume (MPV); mean platelet mass (MPM); mean platelet component (MPC); immature platelets (RtcPlts)] obtained by automation with the ADVIA 2120 and specific biomarkers for sepsis [white blood cells (WBCs); neutrophil granulocytes (NGs); presepsin (PSP); procalcitonin (Pct); C-reactive protein (CRP)] and for SCA (hs cTnI). Results: Platelet indices (RtcPlts, MPV, MPM) were significantly altered (p > 0.005) in patients with suspected sepsis and patients with ACS compared to control subjects; however, no statistically significant difference was observed between the two groups of patients with disease. Cutoff values (ROC curves) were obtained for platelet indices that best discriminated healthy subjects from subjects with severe infection or ACS. Conclusions: Our data show that, in subjects with suspected sepsis and ACS at disease onset, a state of early platelet activation exists that is not disease-specific. Immature platelets (RtcPlts) and the platelet indices MPM and MPV, provided by the ADVIA 2120 hematology analyzer, showed high sensitivity in subjects with suspected sepsis or ACS at disease onset.

Alzheimer’s disease and tauopathies are partlycaused bytau protein fibrillation. The tau’s PHF6/β1 sequence 306VQIVYK311 plays a central role in protein self-assembly,acting as a nucleation center. We aimed to identify new therapeutichexapeptides that inhibit tau fibrillation by targeting the 306VQIVYK311 nucleation site. We designed hexapeptide batchesderived from PHF6, with varying sequences but preserving key aminoacid positions involved in the tau nucleation process. These hexapeptideswere characterized and classified using a newly optimized biochemicalmethod that we developed. Soluble hexapeptides were preselected becauseof their therapeutic potential and were selected by using the in vitro PHF6/β1 fibrillation model. Hexapeptidesstrongly inhibiting fibrillation rates at substoichiometric levelswere selected as leads. Unlike related peptides classified as amyloids,the leads were found to be completely innocuous to neuroblastoma celllines, even at high concentrations. Hexapeptides selected as leadsare promising candidates for therapeutic purposes and can be usedto develop molecules for biochemical diagnosis and probes for positronemission tomography (PET) imaging in the context of tauopathies, particularlyAlzheimer’s disease.

Abstract Background Biochemical determinations of urinary amino acid excretion patterns may be required to diagnose and manage amino acid transport disorders. A simplified process for testing home collected urine specimens would benefit this patient community. We describe the validation of a volumetric absorptive microsampling (VAMS) strategy for the analysis of creatinine and several amino acids (N=22) in dried urine. Methods 30 µL of urine were volumetrically sampled and dried on two VAMS tips from a Mitra device (Neoteryx). An ultra-sonication based solvent extraction procedure was optimized to remove the creatinine and amino acids from the dried urine. Each were respectively quantified in a biochemical genetics laboratory using established clinical assays on a CobasPro (Roche) and MassTrak ultra-performance liquid chromatography (UPLC) amino acid analysis (AAA) solution (Waters). Performance of the VAMS strategy was determined through an assessment of accuracy, precision and stability. The effects of ground transit (time, relative humidity (% RH), and temperature) on dried microsampled urine was also examined. The devised VAMS strategy was applied to urine collected from a patients with lysinuric protein intolerance (LPI, OMIM # 222700), cystinuria (OMIM # 220100), and phenylketonuria (PKU, OMIM # 261600). Results Creatinine measured from microsampled dried urine had an average recovery of 104 ± 15% relative to neat urine. Accurate urine creatinine results were obtained from dried microsamples of archived College of American Pathology (CAP) and ERNDiM proficiency testing material. A 60:40 (v/v) water:methanol pH 11 extraction solvent provided the highest average amino acid recovery. The accuracy of the creatinine corrected amino acid results derived from the VAMS tips relative to neat urine was 107 ± 13%. The average inter-day precision (CV%) of the amino acids and creatinine was 12.4% and 7.7%, respectively. The average 10 day storage stability at 5.6°C/89.3%RH, 20.6°C/50.7%RH, and 39.8°C/18.7%RH were 111%, 107%, and 110% for the amino acids and 95%, 96% and 98%, for creatinine, respectively. Dried urine specimens were shipped from different locations in Massachusetts, Rhode Island, and New Hampshire to our laboratory for testing. The maximum transit duration, temperature, and %RH experienced were 6 days 22 hours 25 minutes, 47°C and 71.1%RH, respectively. Amino acids and creatinine were stable in the microsampled dried urine under all shipping conditions, with average recoveries of 104 ± 9% and 102 ± 6% relative to neat urine. Appropriate marked elevations in arginine, cystine, lysine, and ornithine were respectively observed in the urine of LPI and cystinuria patients and were consistent with the biochemical diagnosis. Marked elevation in phenylalanine was also identified in the dried urine from a PKU patient. Conclusion Creatinine corrected urine amino acid results from the microsampled dried urine testing strategy were accurate relative to traditional analyses of neat urine specimens. Testing dried urine from home collected specimens may be appropriate for patients with amino acid transport disorders.

Diagnosis of liver diseases from liquid biopsy remains a significant clinical challenge due to the limitation in the quantification of endogenous biomarkers and the expensive testing methods. Here, we demonstrate the sensing of endogenous blood plasma fluorophores in the presence of carbon quantum dots (CQDs) by the localized surface plasmon resonance (LSPR) method. The enhancement in the emission of endogenous fluorescence signals in the presence of CQDs can be proposed as a simple and rapid method for diagnosing liver diseases. The performance of the sensor has been validated from the interaction and energy transfer between CQDs and endogenous fluorophores by the emission intensity ratio of NADH and FAD endogenous fluorophores, which are the key biomarkers in liver diseases. This ratio determines the redox state of the cell. The shift in the redox ratio determines the metabolic state of the cells, which helps in the discrimination of cancer cells from normal cells. The changes in intensity by resonance energy transfer statistically validated the discrimination between healthy and liver-diseased plasma conditions of cirrhosis and hepatocellular cancer. Selectivity was documented toward fluorescence enhancement with a limit of detection of 2.3 μM. The results show that the simple and rapid sensing of endogenous fluorophores with high sensitivity and specificity has a strong potential for the biochemical diagnosis of liver diseases.

Objective and backgroundWe present our experience with the first five parathyroidectomies performed in Kuwait using the transoral endoscopic vestibular approach.MethodsRetrospective data collection of trans-oral endoscopic vestibular parathyroidectomies was performed at a single institution in Kuwait. Patient eligibility was determined by previously published exclusion criteria. Information on patient demographics, perioperative management, and complications was collected and reviewed.OutcomesIn our case series, we present five patients who underwent transoral endoscopic parathyroidectomy via the vestibular approach. All included patients had a biochemical diagnosis of primary hyperparathyroidism and two concordant localizing studies demonstrated a single parathyroid adenoma. All patients were above 18 years of age, had no previous neck surgery, and were not on anticoagulants. No intraoperative complications were reported, and the mean operative time was 180 minutes. Postoperatively, four patients were discharged on the same day while one patient was discharged on postoperative day 2. During follow-up, no complications were reported, and the patients reported satisfactory cosmetic results. Finally, parathyroid adenoma was confirmed in the final histopathology report in all five cases.ConclusionThe transoral endoscopic parathyroidectomy vestibular approach (TOEPVA) is a viable, safe, and cosmetically advantageous option for parathyroidectomy in select patients. Careful patient selection is crucial, with criteria including a single adenoma identified on preoperative imaging, and no history of neck surgery or anticoagulant use. Further research is needed to clarify TOEPVA’s role in the surgical management of primary hyperparathyroidism and to explore its long-term outcomes in a larger, diverse patient population.

BackgroundBenign acute childhood myositis (BACM) is a rare condition that usually follows viral infections, predominantly affecting school-aged males. At onset, patients typically complain of soreness in the lower limbs and bilateral calves, with gait abnormalities such as refusal to bear weight, a wide-based gait, or toe walking. This is a generally self-limiting condition, but it may require hospitalization for the initiation of intravenous hydration in severe cases. Renal involvement due to rhabdomyolysis is extremely rare. The diagnostic work-up is often limited by the lack of awareness among pediatricians. This study aimed to describe its epidemiological and clinical characteristics, summarizing cases before and after the COVID-19 pandemic, and providing suggestions for the management of this condition.MethodsThis retrospective multicenter study used data from the AULSS 7 Pedemontana database. We included consecutive patients with clinical and biochemical diagnosis of BACM who were admitted to the Emergency Departments of three Italian hospitals between January 1, 2012, and December 31, 2024. Patients were identified through an extensive search using discharge codes according to the International Classification of Diseases, 9th Revision, Clinical Modification. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 21 (Released 2013; IBM Corp., Armonk, New York, United States).ResultsA total of 55 episodes of childhood myositis affecting 51 patients were identified. Most patients exhibited fever, rhinitis, pharyngitis, asthenia, and hyporexia; a smaller proportion presented with gastrointestinal symptoms. Consistent with the current literature, the predominant symptom of myositis was lower limb pain (n = 49, 89%), followed by refusal to ambulate (n = 30, 55%), often characterized by a wide-based gait (n = 17, 31%), typically following febrile illness. The incidence apparently increased in the post-pandemic period, as did the mean creatine phosphokinase levels increase from admission (928 IU/L vs. 146 IU/L, p = 0.03). A slower normalization of creatine phosphokinase values was also observed during the post-pandemic period (8.5 days vs. 4.2 days, p = 0.004). A higher hospitalization rate was noted in the post-pandemic group (n = 21, 70%) compared to the pre-pandemic group (n = 12, 48%), although this difference did not reach statistical significance (p = 0.10). The need for hospitalization was directly associated with elevated creatine phosphokinase levels (p = 0.05), renal impairment (p = 0.05), elevated blood urea levels (p < 0.0001), older age (p = 0.04), and inversely correlated with the presence of gastrointestinal symptoms (p = 0.001).ConclusionWhile it remains benign, a standardized approach is needed for childhood myositis diagnosis and management, balancing the risks of unnecessary hospitalizations and potential complications. All patients should undergo blood tests along with a urine dipstick, electrocardiogram, and, if possible, influenza A/B swab testing. Patients with mild symptoms, low muscle enzyme levels, no renal impairment, and good family compliance may be discharged home with parental reassurance about the benign nature of the condition. Otherwise, we suggest hospitalization or short-term observation for intravenous hydration and laboratory monitoring. Further research is warranted to elucidate potential post-pandemic changes in disease presentation.

ABSTRACTIntroductionCurrently, it is unclear whether plasma free or 24‐h urinary fractionated metanephrines are preferable for diagnosis of phaeochromocytoma/paraganglioma (PPGL) in children.ObjectivesTo investigate whether measurements of plasma free and 24‐h urinary fractionated metanephrines are reliable tests for screening for PPGL in children.MethodsThis retrospective study included a cohort of 138 paediatric patients (5 to 18 years), 64 with and 74 without PPGL. Data included sex, age, plasma concentrations of free metanephrines, and genetic test results. For a subset of 89 children tested for PPGL, concentrations of 24‐h urinary fractionated metanephrines were also available. For patients with PPGL, data also included tumour location, size, catecholamine tumour phenotype, and presence of recurrent and/or metastatic disease.ResultsAmong children with PPGL, results of plasma metanephrines showed larger fold increases of normetanephrine above the upper cut‐off compared to the urinary metabolites (9.5‐fold vs 7.1‐fold, p < 0.001). Plasma metanephrines showed a diagnostic sensitivity of 92% and specificity of 96%, whereas for urinary metanephrines sensitivity and specificity of 92% and 91% respectively. Sub‐analysis of intra‐individual temporal measurements of metabolites showed that subsequent increases of plasma normetanephrine may be associated with early‐stage development of a noradrenergic PPGL.ConclusionsPlasma free and 24‐h urinary fractionated metanephrines are both reliable screening tests for PPGL in children and adolescents. The plasma panel may be useful for early detection of noradrenergic PPGL relevant for children tested within surveillance programs due to hereditary risk of noradrenergic tumours.

Broadband near-infrared (NIR) light sources based onphosphor-convertedlight-emitting diodes are highly desirable for biochemical analysisand medical diagnosis applications. However, thermal quenching remainsa demanding challenge for developing efficient NIR phosphors. Herein,we report the enhancement of both quantum efficiency and thermal stabilityin Cr3+-activated K2SrP2O7 phosphors through a heterovalent substitution strategy by replacingSr2+ with Al3+ in K2Sr1–xAlxP2O7 (0.05 ≤ x ≤ 0.2) to obtainoptimized broadband NIR emission. Structural modulation via Al3+ substitution leads to the optimized composition, K2Sr0.88Al0.1P2O7:0.02Cr3+, which emits across a broad NIR range of 650–1100nm peaking at 807 nm with a full width at half-maximum of ∼130nm under 448 nm excitation. Remarkably, its emission intensity at150 °C remains 120% of the initial value at room temperature,demonstrating a rare antithermal-quenching behavior. Temperature-dependentXRD studies further reveal that Al3+ substitution effectivelysuppresses lattice expansion at elevated temperatures, indicatingenhanced lattice stability under thermal excitation. Detailed structuraland spectral analyses show that the substitution enhances local sitesymmetry, reduces electron–phonon coupling, increases thermallyinduced absorption probability, and fortifies energetic barriers againstnonradiative transitions. These synergistic effects collectively endowthis NIR phosphor with a superior thermal stability. Furthermore,NIR light-emitting diodes fabricated with this phosphor exhibit strongpotential for applications in information identification, nondestructivedetection, and night vision technologies. This study demonstratesa local structure engineering strategy for designing thermally robustCr3+-activated NIR phosphors, offering valuable insightsinto material discovery and NIR spectroscopy device development.

The article presents a family case of HAE with serine endopeptidase C1 inhibitor deficiency in a mother and son. Hereditary angioedema (HAE) is a hereditary disease caused by a defect in the SERPING1 gene (Serpin Peptidase Inhibitor, Clade G (C1 Inhibitor). Changes in this gene lead to pathological functionality or deficiency in the synthesis of the of the protein C1 esterase inhibitor. The function of the C1 Inhibitor protein is to create a proteolytic inactive stoichiometric complex with C1r or C1s proteases, which activates complement, blood coagulation, fibrinolysis, and kinin production. The disease is manifested by the rapid formation of swellings in various places of the body. According to Mansour Ali and colleagues, among pediatric patients, over 50% of cases manifest before the age of 10, and biochemical diagnosis is advisable from the age of 1 year. In the family history, 37-year-old woman has a syndrome of abdominal ischemia with attacks of acute pain syndrome, attacks of angioedema with repeated urgent parenteral applications of antihistamines and corticosteroids. She was referred for an examination to the faculty clinic for recurrent cases of Quincke's edema, where C1INH deficiency was detected in her blood. She confirmed NM_000062.3:p.496_497insGACA; p.Asn166Argfs*92 heterozygous sequence change during molecular genetic research of DNA, by the method of Sanger sequencing in the SERPING1 gene. Mother's family history is complicated: her grandmother died at the age of 50 due to acute respiratory failure due to Quincke's syndrome, mother's sister died at the age of 32 from a similar condition as her mother. During the immunological examination, a C1INH deficiency was detected in the mother, and during molecular genetic research, DNA analysis, using the Sanger sequencing method in the SERPING1 gene, confirmed a heterozygous sequence change. In the 7 year old son examination revealed a low concentration of complement C3 and C4, and extremely low serum concentration of C1INH, other results of serum immunoglobulins IgG, IgA, IgM, C-reactive protein were normal, celiac disease and autoimmune thyropathy were excluded. His genetic examination revealed a heterozygous sequence change in the SERPING1 gene. The variant identified was not previously described in association with HAE at position 257. In addition to the above changes, the subject also had the variant NM_000062.3:с.468СТ:p.Ala165 with a population share of less than 1%. Summarizing the results of laboratory examinations and the conclusions of narrow-profile specialists, the patient has a confirmed diagnosis of hereditary angioedema with C1 inhibitor deficiency, according to ICD-10 D841 defect of the complement system. The family was given the drug Berinert for emergency parenteral treatment in case of boy's first attack, the district pediatrician and the doctors of the children's department were informed about the dosage of the drug and the course of treatment. The treatment plan consists of parenteral administration of human C1 inhibitor made from donor plasma at a dose of 20 IU/kg at a rate of 4 ml/min. Conclusions. Early diagnosis of HAE-C1-INH should be performed in all children aged 1 year and older if their parents have recurrent attacks of angioedema. Timely and repeated application of C1 inhibitor concentrate in patients with confirmed NEA-C1-INH allows to prevent severe attacks of laryngeal angioedema and to prevent fatal cases.

The biochemical diagnosis of porphyria is based on the analysis of porphyrins in urine, feces, and blood using fluorometry and spectrometry. High-performance liquid chromatography (HPLC) with fluorescence detection has been used since the 1980s as standard procedure for separation of porphyrin isomers and classification of the different types of porphyria since each type of porphyria presents a characteristic HPLC isomer distribution either in urine, plasma or feces. We present a unified collection of chromatograms as an aid for porphyria classification in laboratories using HPLC equipment. Biological samples were collected according to approved hospital protocols, and analyzed by reverse-phase HPLC with fluorescence detection, using an unused dedicated chromatographic column BDS-Hypersil™ C18 and reproducing, with minor variations, the conditions originally reported by Lim and Peters in 1984. With the chromatograms, we include a concise explanation of the changes observed. When inter-individual variation is frequent, we include for clarification chromatograms of two different individual samples. Additionally, we present chromatograms showing abnormalities of porphyrin metabolism in patients without porphyria. We add our collection to the literature, as a visual guide to facilitate porphyria diagnosis and classification though understanding of the key metabolic changes. Our aim is to support education of new experts in the porphyria field increasing diagnostic accuracy and ultimately leading to improved patient outcomes and management.

The term NeuroCOVID was coined to describe the neurological consequences observed in COVID-19 patients. Numerous patients infected with SARS-CoV-2 reported olfactory dysfunction as the first symptom preceding clinical manifestations, such as cough and fever, or even the only symptom, suggesting the sudden loss of smell or hyposmia as an important predictive factor for COVID-19 infection. Several patients developed long-term olfactory impairment, but to date there is not available a biochemical diagnosis of anosmia. The aim of this pilot study is to investigate the association between neurofilament light-chain (NfL) serum levels and the olfactory dysfunctions in post-COVID-19 patients. This study recruited patients who developed COVID-19 between January 2020 and August 2021. They were evaluated between October 2022 and March 2023 by Sniffin’ Sticks tests to investigate deficits of odor identification, discrimination, and threshold and serum NfL biomarker measurement to assess a neuronal damage. Out of 27 patients, 11 were affected by post-viral permanent olfactory dysfunction (named Od-post-COVID-19) and 16 healed from the infection without residual Od problem, as a control group. We observed an increased levels of NfL 16.02 ± 1.91 pg/mL in Od-post-COVID-19, suggesting that NfL to be recognized as a biomarker of post-viral olfactory dysfunction, supporting the diagnostic process of NeuroCOVID, joined with other well-known neurological biomarkers and/or innovative investigative approaches.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, with metabolic-dysfunction-associated steatohepatitis (MASH) and alcohol-related liver disease (ALD) emerging as major etiologies. This review explores the epidemiological trends, pathogenesis, and clinical management of HCC arising from MASH and ALD, highlighting both the shared and distinct mechanisms. MASH-HCC is driven by metabolic dysregulation, including obesity, insulin resistance, and lipotoxicity, with genetic polymorphisms such as PNPLA3 and TM6SF2 playing critical roles in disease progression. ALD-HCC, in contrast, is propelled by the toxic byproducts of ethanol metabolism, including acetaldehyde and reactive oxygen species, which induce chronic inflammation, and fibrosis. Both conditions also involve immune dysregulation, gut dysbiosis, and increased intestinal permeability, contributing to hepatic carcinogenesis. The review emphasizes that, while there is consensus regarding the screening of HCC in cirrhosis patients, there is lack of consensus on screening strategies for non-cirrhotic MASH patients who are also at risk for HCC. This underscores the importance of the early detection of cirrhosis using advanced diagnostic tools such as transient elastography and fibrosis scores. Current therapeutic approaches, ranging from surgical resection, liver transplantation, and locoregional therapies to systemic therapies like immune checkpoint inhibitors, are discussed, with an emphasis on the need for personalized treatment strategies. Finally, the review highlights future research priorities, including the development of novel biomarkers, exploration of the gut–liver axis, and deeper investigation of the interplay between genetic predisposition and environmental factors. By synthesizing these insights, the review aims to inform multidisciplinary approaches to reduce the global burden of MASH- and ALD-related HCC and improve patient outcomes.