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Unraveling a Diagnostic Enigma: A TECPR2 Case Solved Through Multi-Omic Genomics.

TECPR2 is a key regulator of autophagy, encoded by the TECPR2 gene. Pathogenic variants in this gene have been linked to a rare hereditary sensory and autonomic neuropathy with intellectual disability (HSAN9). We report a teenage female with a syndromic intellectual disability disorder associated with neuromuscular abnormalities. Multi-omics analysis including genomics, transcriptomics, and proteomics, together with muscle biopsy from the affected individual, were used in this clinical case. Through trio exome sequencing we identified two heterozygous variants in the TECPR2 gene, NM_014844.4: c.480G>A; p.(Gln160=) and c.2846C>A; p.(Ala949Glu). Both were classified as variants of uncertain significance due to the lack of supporting evidence for pathogenicity. Subsequent long-read sequencing phased the variants and confirmed they were in trans. Additional functional studies using RNAseq and proteomics analyses verified the pathogenicity of the variants. This case study demonstrated the value of a multi-omics assisted analysis, which complemented the traditional phenotype-first approach in reaching a definitive clinical diagnosis.

Humans

Topical Carboxytherapy as an Adjunct to Skin Recovery Post-CO2 Laser Fractional Resurfacing.

BACKGROUND: Topical carboxytherapy, a transcutaneous carbon dioxide (CO2) delivery system, may support skin repair and regeneration, yet its role as an adjunct to fractional laser treatment remains underexplored. OBJECTIVE: To investigate the effectiveness and safety of topical CO2 mask (CO2Lift® Carboxy Gel, Lumisque Skincare) in supporting skin recovery and improving clinical outcomes following fractional CO2 laser resurfacing. METHOD: This 12-week randomized, placebo-controlled trial evaluated mild-to-moderate photoaging (n=6 females only). Participants received either topical carboxytherapy (n=4) or standard care (n=2). Assessments included VISIA-CR imaging, biophysical measurements, investigator ratings, and paired (baseline and 4-week) skin biopsies. RESULTS: Topical carboxytherapy accelerated recovery and was well-tolerated, with no major adverse events. VISIA-CR imaging showed accelerated erythema resolution, transepidermal water loss normalized more rapidly, and pH remained stable. Skin histology at week 4 revealed epidermal thickening and rete ridge formation with topical carboxytherapy vs placebo. Investigator ratings demonstrated significantly improved healing, global assessment, and global aesthetic improvement scale scores, with trends toward improvement in photodamage, rhytides, and pigmentation. CONCLUSION: Adjunctive topical carboxytherapy after fractional CO2 resurfacing accelerated healing, improved barrier recovery, and overall aesthetic outcomes. Larger studies are needed to confirm these findings.

Humans

Influenza as a Less Commonly Recognized Cause of Hemophagocytic Lymphohistiocytosis: A Systematic Review of Case Reports and Case Series.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory condition that can be triggered by viral infections. However, influenza is not commonly recognized as a cause of HLH, and there is no comprehensive synthesis of influenza-associated HLH in the literature to guide clinicians. We conducted a systematic search of Pubmed and Embase to identify case reports and case series on influenza-associated HLH, and included 29 articles involving 47 patients. Their age ranged from 2 months to 72 years. 67% were males. Influenza A accounted for 91.3% of the cases, predominantly H1N1 (90.2%). All patients had fever, 60% had anemia, 69.7% had thrombocytopenia, 46.6% had leukopenia, 61.3% had splenomegaly, 71.4% had hypertriglyceridemia, and 94.7% had elevated ferritin levels. 97.6% had hemophagocytosis on biopsy. Antiviral therapy was administered in 89.5% of patients. HLH-directed therapy included corticosteroids (77%), intravenous immunoglobulin (36%), and etoposide (23.1%). Intensive care was required in 95.2% of cases. Overall survival was 53.2%. Survival rate was 50% among patients who received either antiviral therapy alone or HLH-directed therapy alone, compared with 65.4% among those who received both. Further studies are necessary to establish standardized diagnostic and therapeutic protocols for influenza-associated HLH.

Humans

Normoalbuminuric and albuminuric diabetic kidney disease exhibit divergent renal proteomic characteristics: implications for management.

BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is complex. Normoalbuminuric diabetic kidney disease (NADKD) is a special subtype of DKD that often progresses insidiously without detectable albuminuria, posing diagnostic and therapeutic challenges. Its pathogenesis remains unclear. Proteomic analysis of renal tissues may offer insights into its pathogenesis and identify biomarkers. METHODS: Clinicopathological data from 295 biopsy-proven DKD patients were collected and classified into normoalbuminuric (UACR&#xa0;<&#xa0;30&#xa0;mg/g, n&#xa0;=&#xa0;25), microalbuminuric (UACR 30-300&#xa0;mg/g, n&#xa0;=&#xa0;26), and macroalbuminuric (UACR&#xa0;>&#xa0;300&#xa0;mg/g, n&#xa0;=&#xa0;244) groups. Laser microdissection combined with mass spectrometry (LMD/MS) was used to analyze glomerular and proximal tubule proteomics in 5 patients per DKD subgroup and 5 control subjects. Associations with clinical features were examined. RESULTS: Glomerular proteomic analysis revealed that oxidative stress and metabolic pathways (UQCRC1) were upregulated in NADKD group, whereas the complement and coagulation cascades (C3, C5, C6, C9, CFH, CFHR1) were significantly upregulated in the microalbuminuric and macroalbuminuric DKD groups. The proximal tubule proteomics analysis showed that oxidative phosphorylation-related proteins (SDHA, CYCS, UQCRQ) were upregulated in NADKD, and collagen I related proteins (COL1A1, COL1A2) were significantly upregulated. CONCLUSION: Oxidative stress and mitochondrial dysfunction are involved in the progression of NADKD, lesions predominantly located in the tubulointerstitium. The complement pathway participates in the pathogenesis and progression of albuminuric DKD (ADKD). These divergent molecular profiles suggest that NADKD and ADKD may reflect different pathophysiological mechanisms and have important implications for therapeutic strategies in diabetes management.

Humans

IgA Vasculitis with necrotizing arteritis: a multicenter retrospective study from the French Vasculitis Study Group and systematic review of the literature.

IgA vasculitis (IgAV) primarily affects small vessels, but rare cases with necrotizing arteritis (NA) raise questions about overlap with polyarteritis nodosa (PAN). To characterize IgAV with necrotizing arteritis (IgAV-NA) and compare its phenotype with classical IgAV and PAN. We performed a multicenter retrospective study combined with a systematic literature review (1990-2025). Patients fulfilled EULAR/PRINTO/PRES IgAV criteria, had pathological or imaging evidence of NA in small or medium arteries, and were ANCA-negative. Thirty patients were included (7 from databases, 23 from the literature). NA was confirmed by biopsy (n&#x2009;=&#x2009;16) or vascular imaging (n&#x2009;=&#x2009;14). Clinical features, treatments, remission, and mortality were compared with 257 adult IgAV and 196 PAN patients. Median age was 54.5 years. IgAV-NA was characterized by severe manifestations, including gastrointestinal bleeding, perforation, surgical abdomen, neuropathy, pancreatitis, and livedo. Compared with classical IgAV, IgAV-NA showed significantly higher rates of multi-organ involvement and mortality. Compared with PAN, IgAV-NA shared vascular complications but had less fever and neuropathy. Despite arterial involvement, patients did not fulfil PAN criteria. IgAV-NA represents a rare, severe IgAV phenotype with life-threatening complications rather than an IgAV-PAN overlap. Severe or atypical IgAV presentations should prompt vascular imaging and intensified immunosuppression.

Humans

Exploratory proteomic and metabolomic profiling of pleural effusions identifies histone H4 and alanine as promising complementary markers for pleural tuberculosis.

The diagnosis of pleural tuberculosis (Pl-TB) remains challenging. Histopathological analysis and pathogen detection in pleural biopsies are informative but limited. We investigated differentially expressed proteins and metabolites in pleural effusions from patients with Pl-TB, malignancies, and other pathologies. A proteomic analysis of pooled pleural effusions identified 45 proteins exclusively detected or upregulated in Pl-TB samples, many linked to infectious processes. Conversely, 18 proteins were uniquely found or upregulated in malignant pleural effusions, mainly associated with detoxification and hemostasis. To validate these findings, we employed targeted proteomics in individual samples. Eight proteins were validated: S100-A9, histone H4, insulin-like growth factor-binding protein 2, fibrinogen beta chain, ficolin-3, immunoglobulin heavy constant alpha 1, sulfhydryl oxidase 1, and histidine-rich glycoprotein. Additionally, NMR-based metabolomics identified 13 metabolites with differential abundance between Pl-TB and non-TB samples. Notably, N-acetyl-glycoprotein and the branched-chain amino acids, alanine and lysine differed between groups. Proteomic and metabolomic analyses revealed distinct molecular profiles between Pl-TB and non-TB patients, despite intra-group variability. To address this, we applied classification models. Histone H4 and alanine consistently emerged as discriminative features. Overall, this study provides novel insights into the molecular landscape of Pl-TB. The combined quantification of proteins and metabolites may improve differential diagnosis, although should be further validated in larger, independent cohorts before clinical application.

Humans

The neuroendoscopic factors affecting outcome of endoscopic third ventriculostomy in pediatric patients with post infectious hydrocephalus.

BACKGROUND: The role of endoscopic third ventriculostomy(ETV) in infective hydrocephalus remains uncertain. Infection alters cerebrospinal-fluid composition, flow-dynamics, absorptive capacity, undermining the effectiveness of ETV. AIMS AND OBJECTIVES: This study aims to describe the intraventricular morphological findings and its correlation with ETV outcomes in a cohort of paediatric infective hydrocephalus. METHODOLOGY: Total 98 cases of infective HCP underwent ETV, were studied for intraventricular findings. Thin transparent third ventricular floor were considered as type-1, transluscent as type-2, floor with granuloma as type-3 and unidentifiable anatomy as type-4. Infective deposits were sent for histopathology. RESULT: Overall ETV was successful in 46 patients (46.93%). Success rate of ETV in type 1 (72.7%) was better than type-2 (50%) and type-3 (33.3%). The difference between type-1 and type-3 was statistically significant, p&#xa0;=&#xa0;0.01. The success rate in presence of pre-pontine adhesions (46 cases) was 34.7%, significantly lower than the 66.6% observed in their absence (p&#xa0;=&#xa0;0.005). ETV was not successful in all the 7 cases withy type-4 floor. Tissue biopsy confirmed microbiological diagnosis in 13 cases and helped in modifying pharmacological treatment as per culture (two with tuberculosis and three with fungal infection). CONCLUSION: ETV offers a meaningful therapeutic option in post-infectious HCP. Endoscopic appearance of the third ventricular floor and the pre-pontine space may predict its outcome. A thin, transparent floor in the absence of cisternal adhesions is associated with best outcomes, while progressive floor thickening, granuloma formation, and pre pontine fibrosis each correlate with declining success rates. The culture from exudates often helps in achieving organism oriented pharmaco-therapy that improves ETV success rate.

Humans

Diagnostic accuracy of bronchoalveolar lavage fluid-based testing for pulmonary cryptococcosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cryptococcosis(PC) presents diagnostic challenges because of its non-specific clinical and radiological manifestations. Bronchoalveolar lavage fluid (BALF)-based testing, which includes latex agglutination (LA) and lateral flow assay (LFA), offers a minimally invasive diagnostic method, yet its pooled diagnostic accuracy remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Scopus from inception to May 2026. Studies evaluating BALF-based testing for PC with extractable 2 &#xd7; 2 data were included. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Subgroup analyses were performed by testing method and reference standard type. Heterogeneity was evaluated through paired forest plots, HSROC visualization, and exploratory bivariate meta-regression. RESULTS: The pooled sensitivity was 0.87 (95% CI: 0.81-0.91), and the specificity was 0.99 (95% CI: 0.982 - 0.995). The pooled positive likelihood ratio (PLR) was 88.00 (95% CI: 47.39 - 163.42), the negative likelihood ratio (NLR) was 0.13 (95% CI: 0.09 -0.20), and the DOR was 658.50 (95% CI: 285.36-1519.55). No significant threshold effect or publication bias was detected. Exploratory meta-regression suggested a possible assay-method effect in the joint model (P = 0.03), mainly driven by specificity (P = 0.01). CONCLUSIONS: The study demonstrates the high accuracy of CrAg in BALF for the diagnosis of pulmonary cryptococcosis, supporting its role as an important adjunctive diagnostic tool, particularly when tissue biopsy is not feasible or rapid results are needed. Larger prospective studies with standardized protocols are needed to validate these estimates.

Humans

Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.

The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.

Humans

Incidence of Cirrhosis in Fibrotic Metabolic Dysfunction-Associated Steatohepatitis: A Meta-Analysis of Placebo Arms from Randomized Clinical Trials.

BACKGROUNDS AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) with stage F2-F3 fibrosis represents the main target population for emerging pharmacotherapies. However, data on short-term progression to cirrhosis (F4) in this group remain limited. We aimed to evaluate the incidence of cirrhosis in placebo-treated patients with fibrotic MASH in randomized controlled trials (RCTs). METHODS: In this single-arm meta-analysis, we systematically searched PubMed and Cochrane Library from inception to December 13, 2024, for pharmacological Phase&#x2009;&#x2265;&#x2009;2 RCTs reporting cirrhosis events (detected in liver biopsy or clinical signs) among patients with fibrotic MASH receiving placebo. Incidence rates were pooled using generalized linear mixed models with Clopper-Pearson confidence intervals (CIs). RESULTS: We identified a total of 11 RCTs, including 586 patients with fibrotic MASH. Total follow-up was 657.23 person-years (PYs), with 83 cirrhosis events reported. The pooled incidence rate was 13.09 per 100 PYs (95% CI 7.81 to 21.12, I2&#x2009;=&#x2009;75.6%, &#x3c4;2&#x2009;=&#x2009;0.682). In subgroup analysis, the incidence of cirrhosis was 3.40 per 100 PYs in MASH F2 (95% CI 1.10 to 10.02, I2&#x2009;=&#x2009;0%, &#x3c4;2&#x2009;=&#x2009;0) and 17.90 per 100 PYs (95% CI 10.63 to 28.55, I2&#x2009;=&#x2009;70.2%, &#x3c4;2&#x2009;=&#x2009;0.561) in MASH F3, with significant differences between stages (p&#x2009;=&#x2009;0.006). Sensitivity analyses showed consistent estimates. Most RCTs were judged to have a low risk of bias. CONCLUSIONS: This study provides stage-specific data on cirrhosis incidence in fibrotic MASH, highlighting the high short-term risk associated with MASH F3 in trial settings. These data may inform benchmarks to guide event expectations, enrichment strategies, sample size assumptions, and the interpretation of future MASH clinical trials.

Humans

Metabolomic Signatures of Inflammation in Chronic Kidney Disease.

RATIONALE & OBJECTIVE: Inflammation is associated with adverse kidney, cardiovascular, and mortality outcomes. Investigation of the metabolic milieu as it relates to inflammation may provide important insights into these disease processes. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: African American Study of Kidney Disease and Hypertension (AASK), Atherosclerosis Risk in Communities (ARIC) study, and Boston Kidney Biopsy Cohort (BKBC) participants with available metabolomics and inflammatory protein data. PREDICTORS: Baseline blood levels of 718 metabolites. OUTCOMES: Baseline and longitudinal changes in blood levels of tumor necrosis factor receptors 1 and 2 (TNFR1, TNFR2), tumor necrosis factor-alpha (TNF-&#x3b1;), interferon-gamma (IFN-&#x3b3;), interleukins 6, 8, and 10 (IL-6, IL-8, IL-10), uromodulin (UMOD), and epidermal growth factor (EGF). ANALYTICAL APPROACH: Multivariable linear regression and linear mixed-effects models. RESULTS: Among 491 AASK participants (mean age 54 years; 37% women; mean glomerular filtration rate, 45 mL/min/1.73 m2), 367 cross-sectional associations between metabolites and inflammatory proteins were significant after correction for multiple comparisons. The direction of association was mostly positive for TNFR1 (97%), TNFR2 (97%), IL-8 (77%), and IL-10 (100%); negative for UMOD (80%) and EGF (97%); and variable for TNF-&#x237a;, IFN-&#x3b3;, and IL-6. Pathways were distinct for several inflammatory proteins (eg, tryptophan metabolism for TNFR2). Forty-five associations between metabolites and longitudinal change in inflammatory proteins were identified. Notable metabolites included tigylcarnitine and N 2,N 5-diacetylornithine, which were associated with 2-year increases in TNFR1 and/or TNFR2, and 1,5-anhydroglucitol, where lower levels were associated with decreases in UMOD. In ARIC (n = 3,773) and BKBC (n = 413), replication of cross-sectional associations was excellent for TNFR1 (ARIC 83%; BKBC 85%) and TNFR2 (ARIC 64%; BKBC 79%) but poor for IL-8 (ARIC 3%; BKBC 3%). LIMITATIONS: Metabolite data limited to baseline visit; potential for residual confounding. CONCLUSIONS: Using an untargeted approach, multiple metabolites were cross-sectionally and longitudinally associated with inflammatory proteins in persons with chronic kidney disease.

Chronic kidney disease

Characteristics of p53 and Smad4 immunohistochemistry in pancreatic ductal adenocarcinoma and validation by next-generation sequencing.

BACKGROUND: Mutations in four major driver genes -KRAS, CDKN2A, TP53, and SMAD4- are central to the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) and critically inform diagnosis, therapeutic decision-making, and prognostic assessment. Although next-generation sequencing (NGS) is widely regarded as the gold standard for detecting these mutations, its clinical application is often limited by suboptimal analytical efficiency and substantial economic cost. Among these genes, immunohistochemical (IHC) staining for the proteins encoded by TP53 and SMAD4 has been extensively adopted in routine pathology practice. However, standardized IHC pattern classification schemes and rigorous validation of their predictive accuracy for underlying genomic alterations remain lacking in PDAC. METHODS: We retrospectively enrolled 63 PDAC patients and systematically characterized the typical IHC expression patterns of p53 and Smad4. Targeted NGS was subsequently performed on all available tumor specimens, and the resulting mutational profiles were correlated with corresponding IHC findings. Diagnostic performance including sensitivity, specificity and accuracy of p53 IHC for predicting TP53 mutations and of Smad4 IHC for predicting SMAD4 mutations was rigorously evaluated. RESULTS: Among the four canonical driver genes, co-occurring double- or triple-gene mutations were prevalent; within TP53 and SMAD4, missense mutations constituted the most frequent variant type. Using NGS as the reference standard, we validated the diagnostic utility of a three-tiered p53 IHC classification system, particularly in fine-needle biopsy (FNB) specimens. Furthermore, we proposed a novel, refined Smad4 IHC pattern classification that incorporates an "intermediate" category, thereby expanding upon conventional binary interpretation. This new scheme achieved markedly improved mutation prediction accuracy (0.76) compared with traditional approaches (0.57). CONCLUSION: Our study highlights the complementary diagnostic value of p53 and Smad4 IHC relative to molecular testing in PDAC, especially when tissue is limited, as commonly encountered in FNB specimens. The newly established Smad4 IHC classification system, which integrates an intermediate expression category into the conventional two-tier framework, demonstrates superior clinical utility and enhances predictive accuracy for SMAD4 genomic alterations.

Humans

Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study.

OBJECTIVE: Muscle weakness is prevalent in rheumatoid arthritis (RA), osteoarthritis (OA) and sarcopenia (SARC). Endurance exercises may improve mitochondrial function and oxidative capacity, while strength exercises are thought to stimulate myofibrillar protein synthesis. This study aims to compare the effects of strength and endurance exercise and explore the association between muscle characteristics and exercise outcomes in patients with RA, OA and SARC. We hypothesize that responses to endurance and strength exercises in patients with muscle weakness are influenced by intramuscular pathology including muscle morphology, mitochondrial function, and systemic inflammation, based on their disease pathology, potentially requiring personalized training schedules. METHODS: This two-arm, parallel-group exploratory trial will enroll 69 patients (23 RA, 23 OA, 23 SARC), randomized to endurance (n&#x2009;=&#x2009;35) or muscle strength exercises (n&#x2009;=&#x2009;34), using minimization to balance disease type and gender. The 8-week intervention includes two supervised sessions per week using a controlled cable pulley device (Reforter&#x2122;) and fitness equipment, plus one weekly home-based session. The primary outcome is isokinetic muscle strength (peak torque), measured with the Biodex system&#xae;. Secondary outcomes include muscle morphology, mitochondrial function, systemic inflammation and muscle endurance (by Biodex and 6 Minute Walk test). Muscle morphology will be assessed via 3D ultrasound imaging of the vastus lateralis. Mitochondrial function will be analyzed using high-resolution respirometry on muscle biopsies. Systemic inflammation will be measured using multiplex assays or ELISA on serum samples. DISCUSSION: This study will explore differential responses to muscle endurance and muscle strength exercises in patients with RA, OA, and SARC, offering novel insights into the molecular mechanisms of muscle weakness. The findings may help identify potential mechanisms underlying variability in exercise response and provide effect size estimates to guide future confirmatory studies and more targeted exercise interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06480643 (date of registration28-06-24).

Humans

Application of Perioperative Real-Time Fluorescence Imaging to Achieve High-Quality Debridement: A Randomized Control Trial.

OBJECTIVE: To investigate the effectiveness of real-time fluorescence imaging (RTFI)-assisted debridement in managing chronic wounds compared with standard surgical debridement. APPROACH: This study was a patient-blinded, randomized clinical trial conducted from February 17, 2021, to July 30, 2021, on patients with chronic wounds. Patients were randomized to an RTFI group (M group) or conventional group (C group). The primary outcomes were as follows: percentage of residual bacterial area (preoperative and postoperative), number of debridements, high-quality debridement ratio, operation duration, and wound healing duration. RESULTS: A total of 100 patients were enrolled in both groups. No significant difference in the percentage of preoperative residual bacterial area or high-quality debridement ratio was seen. The M group underwent debridement an average of 2.6 times and had a significantly longer duration of operation (33.5 &#xb1; 12.7 min) than the C group (29.9 &#xb1; 10.4 min; p = 0.031). The postoperative residual bacterial area was significantly lower in the M than in the C group (6.83% &#xb1; 1.39% vs. 30.0% &#xb1; 12.37%, respectively; p < 0.001). The M group required significantly fewer wound healing days (49.2 &#xb1; 25.3 vs. 63.0 &#xb1; 27.9, p < 0.001). Secondary outcomes also demonstrated statistically significant differences in total hospitalized days (17.5 &#xb1; 9.3 vs. 21.5 &#xb1; 12.5, p < 0.01), days of antibiotic use (15.5 &#xb1; 8.7 vs. 18.7 &#xb1; 6.7, p < 0.01), and reinfection rates (4 of 100 vs. 22 of 100, p < 0.001). INNOVATION: RTFI can detect signals from normal skin components and bacterial metabolites. Therefore, interpretation of RTFI results should be correlated with the clinical condition. RTFI is associated with high-quality debridement. This technique can also be applied in targeted biopsy and in training young staff to mature debridement procedures. CONCLUSION: RTFI in debridement is associated with favorable clinical outcomes and may have a positive influence on chronic wound healing.

Humans

Antibody-drug conjugates against multidrug-resistant cancers: Biomarker-guided patient selection, payload engineering, linker chemistry, and bystander effects.

Antibody-drug conjugates (ADCs) are one of the most significant advancements in modern cancer therapeutics. Combining the target selectivity of monoclonal antibodies with the cytotoxic potential of payloads, ADCs effectively kill cancer cells and offer hope to patients with even refractory cancer types. Beyond simply increasing the number of therapeutic options available for cancer patients, ADCs have become a powerful frontline agent in overcoming multidrug resistance (MDR). As one of the most challenging obstacles to effective cancer care, MDR is mediated by ATP-binding cassette (ABC) transporter-mediated drug efflux, target-based mutations, and dysregulated apoptosis. The clinical success of ADCs specifically engineered to overcome MDR, including in heterogeneous tumors and cancer cells that exhibit bypass signaling, is well established. This is especially evident with trastuzumab deruxtecan (T-DXd) in HER2-low, HER2-positive, and HER2-mutant cancers; sacituzumab govitecan (SG) in TROP2-expressing triple-negative breast cancer (TNBC) and urothelial carcinoma; and enfortumab vedotin in Nectin-4-positive bladder cancer. By overcoming MDR, ADCs have enabled more effective treatment algorithms across multiple malignancies. Most importantly, the clinical application of ADCs has become inextricably linked to cancer genomics. HER2 testing has evolved from a two-tiered system to a continuous spectrum including HER2-ultralow, HER2-low, HER2-positive, and ERBB2-mutant categories. Each of these categories exhibits different eligibility guidelines for ADC patient selection. As cancer cells continue to evolve and develop resistance to even ADCs through mutations and variants, researchers and clinicians have used pharmacogenomics to predict ADC response and resistance. To define the genomic architecture of ADC-resistant tumor subpopulations, single-cell transcriptomic studies and liquid biopsy approaches are being used to enable real-time examination of the tumor genome during ADC therapy, thereby optimizing treatment and circumventing resistance driven by emerging mutations and variants. This review provides a comprehensive analysis of the molecular structure of ADCs, the pharmacological principles underlying their potent cytotoxic activity against MDR cancer cells, the genomic and transcriptomic biomarkers that guide ADC patient selection, and the emerging resistance mechanisms that will shape the next generation of promising ADC development.

Humans

Ketamine Plus Midazolam versus Fentanyl Plus Midazolam for Sedation and Analgesia during Image-guided Procedures in Interventional Radiology: Randomized Clinical Trial.

Background Opioid-benzodiazepine regimens remain common for radiologist-administered procedural sedation despite respiratory and analgesic effectiveness concerns. Purpose To compare intraprocedural pain and patient-reported experience between ketamine/midazolam and fentanyl/midazolam during image-guided procedural sedation. Materials and Methods This randomized clinical trial was conducted at a single academic center between June 2025 and February 2026. Adults undergoing image-guided lung or bone biopsy or abscess drainage were randomized to fentanyl/midazolam or ketamine/midazolam administered by interventional radiologists. Procedures were performed using US, CT, CT fluoroscopy, or combined CT and US guidance. The primary outcome was maximum intraprocedural pain (0-10 on the Numeric Rating Scale). Secondary outcomes included sedation depth, physiologic parameters, oxygen desaturation, patient-reported experience assessed using a modified Heidelberg questionnaire, and complications. Results Among 264 randomized procedures (132 procedures per group) in 260 participants (median age, 68 years [IQR, 61-75 years]; 135 [52%] female), ketamine/midazolam resulted in lower maximum intraprocedural pain than fentanyl/midazolam (mean difference, -1.4 points [95% CI: -2.0, -0.8]; P < .001). Pain scores greater than 4 occurred less frequently with ketamine/midazolam (2.3% vs 17%; absolute difference, 14 percentage points [95% CI: 8, 21]; P < .001). Ketamine/midazolam was associated with higher nadir oxygen saturation (mean difference, +1.4% [95% CI: 0.6, 2.2]; P = .001) and fewer oxygen desaturation events below 90% (three [2.3%] vs 13 [9.8%]; absolute difference, 7.6 percentage points [95% CI: 1.9, 13.3]; P = .02). Ketamine/midazolam produced deeper sedation and higher intraprocedural systolic blood pressure. Hallucinations occurred more frequently with ketamine/midazolam (15 [11.4%] vs five [3.8%]; absolute difference, 7.6 percentage points [95% CI: 1.3, 13.9]; P = .03), though overall procedural comfort, reduced recall, and perceived adequacy of sedation were improved. Procedure-related and sedation-related complications did not differ between groups. Conclusion Radiologist-administered ketamine/midazolam during image-guided procedural sedation improved analgesia and patient-reported experience with fewer hypoxemic events and no increase in complications compared with fentanyl/midazolam. Clinical trial registration no. NCT07040163

Aged

Efficacy of dapagliflozin on hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease: a pre-specified single-arm analysis from a randomized controlled trial.

AIM: To evaluate the association of dapagliflozin therapy with changes in hepatic steatosis and non-invasive fibrosis surrogate markers in patients with type 2 diabetes mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) over 12&#xa0;months. METHODS: This is a pre-specified single-arm analysis from a randomised, open-label, parallel-group trial. Of 54 participants randomised to dapagliflozin 10&#xa0;mg daily, 50 (92.6%) completed the 12-month follow-up and were included in the per-protocol analysis. Assessments at baseline, 3, 6, and 12&#xa0;months included transient elastography (CAP and LSM), ultrasonography, and biochemical tests. Primary endpoints were changes in hepatic steatosis (CAP) and non-invasive fibrosis surrogates (LSM). RESULTS: Significant reductions were observed in hepatic steatosis (CAP: 316.7 to 245.7&#xa0;dB/m; mean change&#xa0;-&#xa0;71.02&#xa0;dB/m, 95% CI: -63.4 to&#xa0;-&#xa0;78.6; p&#xa0;<&#xa0;0.001) and in liver stiffness as a non-invasive fibrosis surrogate (LSM: 8.59 to 7.28&#xa0;kPa; mean change&#xa0;-&#xa0;1.31&#xa0;kPa, 95% CI: -0.92 to&#xa0;-&#xa0;1.70; p&#xa0;<&#xa0;0.001). Improvements were also observed in glycaemic control, body weight, lipid profile, liver enzymes, ultrasonographic steatosis grading, and serum fibrosis markers. Genitourinary infections were the most frequently reported adverse events (32%); no serious adverse events were recorded. CONCLUSIONS: Dapagliflozin was associated with significant improvements in hepatic steatosis, non-invasive fibrosis surrogate markers, metabolic parameters, and liver function in T2DM patients with MASLD over 12&#xa0;months. These findings provide region-specific evidence for an Indian population and support further controlled investigation. However, these findings should be interpreted in light of the pre-specified single-arm design of this analysis, the open-label methodology, relatively small sample size, and the absence of liver biopsy confirmation.

Humans

Clinical features and outcomes of patients with anti-neutrophil cytoplasmic antibody-positive systemic lupus erythematosus from a single-center retrospective study.

INTRODUCTION: The role of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic lupus erythematosus (SLE) remains unclear. ANCA positivity has been linked to more severe disease and possible overlap with ANCA-associated vasculitis, but available data are inconsistent. METHODS: We conducted a retrospective single-center study of SLE patients treated at the University Hospital in Krak&#xf3;w (2012-2022). Patients fulfilled the 2019 EULAR/ACR criteria. ANCA positivity (anti-MPO or anti-PR3) was confirmed by ELISA. Clinical features, laboratory findings, treatment, and outcomes were analyzed. RESULTS: Among 1039 SLE patients, 18 (1.73%) were ANCA-positive (anti-MPO, 72.22%; anti-PR3, 27.78%). Most ANCA-positive SLE patients were female (88.89%), with a median age at disease onset of 35.5&#xa0;years. The most common manifestations in ANCA-positive cases were hematological abnormalities (100%), constitutional symptoms (88.89%), and joint involvement (88.89%). Renal involvement was observed in 72.22% (n&#x2009;=&#x2009;13) of ANCA-positive SLE patients; however, lupus nephritis was confirmed by kidney biopsy in only seven cases. Vasculitis was rare (5.56%). Anti-dsDNA (61.11%) and anti-SSA (50%) were the most frequent autoantibodies. No significant differences were found between anti-MPO and anti-PR3 subgroups. Most ANCA-positive patients received glucocorticoids (94.44%), cyclophosphamide (61.11%), and antimalarials (61.11%). No statistically significant differences were observed between the ANCA-positive and ANCA-negative groups (p&#x2009;>&#x2009;0.05 for all parameters). CONCLUSIONS: ANCA positivity in SLE is rare and predominantly associated with anti-MPO antibodies. It is linked to frequent renal involvement but infrequent vasculitis. No differences were observed between ANCA subtypes, suggesting no distinct clinical phenotype. Key Points &#x2022; ANCA positivity was rare in this systemic lupus erythematosus cohort (1.73%) and was predominantly associated with anti-MPO antibodies rather than anti-PR3 antibodies. &#x2022; No significant differences in demographic characteristics, clinical manifestations, comorbidities, or autoantibody profiles were observed between ANCA-positive and ANCA-negative patients. Similarly, no significant differences were identified between the anti-PR3-positive and anti-MPO-positive groups. &#x2022; ANCA-positive SLE was commonly associated with the need for intensive immunosuppressive treatment, highlighting its potential relevance as a marker of severe disease course.

Humans