Abstract This study investigates the bleaching of pearl millet straw fibres, comparing conventional hydrogen peroxide wet processing with an alternative dry ozone treatment. The inherent golden yellow colour of these novel fibres necessitates bleaching before dyeing applications. The research examined critical ozone treatment parameters, including pH, moisture content, exposure time and power settings to optimise whiteness outcomes. Both bleaching methods achieved comparable levels of whiteness and fibre strength retention. Comprehensive characterisation of fibres through SEM–EDX, XRD and FTIR techniques revealed substantial structural modifications after bleaching treatment. Bleaching increased fibre crystallinity from 60.5% to approximately 65.2%. FTIR analysis demonstrated pronounced lignin reduction in ozone‐treated samples, while SEM analysis revealed distinct morphological changes including fibril separation and micropore formation. These structural modifications enhanced the water absorption properties of ozone‐bleached fibres. The findings establish dry ozone bleaching as an effective and environmentally sustainable alternative to conventional peroxide treatment, achieving comparable technical performance while eliminating chemical usage and water consumption. This development presents significant implications for eco‐friendly bleaching of natural fibres at industrial scale.

Common bile duct stones (CBDS) are a common finding during laparoscopic cholecystectomy, yet the optimal treatment strategy remains under debate. In Sweden, CBDS are usually managed by intraoperative endoscopic retrograde cholangiopancreatography using the rendezvous technique (RV-ERCP). An alternative treatment approach is laparoscopic transcystic placement of an endobiliary stent with postoperative ERCP (TCStent-ERCP). The aim of this study was to compare these two treatment strategies in terms of complication rates. Data were extracted from the Swedish Registry for Gallstone surgery and ERCP (GallRiks) from three different hospitals between 2010 and 2023. All cholecystectomies in which CBDS were detected intraoperatively and ERCP was carried out, either during the same session or later, were collected. Procedures involving TCStent-ERCP or RV-ERCP were identified. Complications within 30days related to the cholecystectomy as well as to the ERCP were compared between the two groups. In total, 929 patients were included. The overall complication rates were 21/183 (11%) in the TCStent-ERCP group and 140/746 (19%) in the RV-ERCP group. In adjusted multivariable regression analysis, fewer overall complications were found using the TCStent-ERCP strategy compared with RV-ERCP (OR 0.60, 95% CI 0.35-0.97). However, no statistically significant differences were observed between the groups for surgical complications or post-procedural pancreatitis. Transcystic stenting with postoperative ERCP appears to be a safe alternative to intraoperative rendezvous ERCP for the management of CBDS encountered during intraoperative cholangiography. This might be beneficial in surgical units where resources required for unplanned ERCP are limited or lacking.

Patients with moderate-to-severe atopic dermatitis (AD) who discontinue dupilumab need additional therapeutic options. Lebrikizumab's distinct mechanism of action may provide that alternative treatment. We evaluated efficacy and safety of lebrikizumab in adults and adolescents with moderate-to-severe AD previously treated with dupilumab. In the open-label ADapt trial, patients who discontinued dupilumab due to inadequate response, adverse events (AEs)/intolerance, or other reasons received lebrikizumab 250-mg every 2weeks (Q2W) following 500-mg loading dose at baseline/week2, through week16, with optional topical therapy. From weeks16-24, responders (≥ 75% improvement in Eczema Area and Severity Index [EASI75] or Investigator's Global Assessment score 0/1 with ≥ 2-point improvement from baseline) received lebrikizumab every 4weeks; inadequate responders continued lebrikizumab Q2W. The primary endpoint was EASI75 at week16 in the intent-to-treat population; EASI75 was also analyzed by reason for dupilumab discontinuation. Secondary and exploratory efficacy endpoints were assessed throughout. Among the 86 patients enrolled, primary reasons for stopping dupilumab were inadequate response (n = 48, 55.8%), AEs/intolerance (n = 14, 16.3%), and other reasons (n = 24, 27.9%). Fifty-nine patients (68.6%) completed week16; 52 patients (60.5%) completed week24. At weeks16 and 24, respectively, response rates were 57.4% (35/61) and 60.0% (33/55) for EASI75; 53.2% (25/47) and 61.5% (24/39) for Pruritus Numeric Rating Scale ≥ 4-point improvement; and 83.0% (44/53) and 83.0% (39/47) for Dermatology Life Quality Index ≥ 4-point improvement. Most treatment-emergent AEs were mild/moderate. Serious AEs and discontinuations due to AEs were reported by 2 (2.3%) and 5 (5.8%) patients, respectively. Of the 10 patients who discontinued dupilumab due to eye-related events, facial dermatitis, or inflammatory arthritis, none reported similar events with lebrikizumab. Results suggest that lebrikizumab provides meaningful improvements in skin clearance, itch, and quality of life in dupilumab-experienced patients with moderate-to-severe AD, with a safety profile consistent with other lebrikizumab phase3 trials. ClinicalTrials.gov identifier, NCT05369403.

Background: Structural heart disease (SHD) significantly increases the risk of life-threatening ventricular arrhythmias (VAs), contributing to sudden cardiac death. Implantable cardioverter-defibrillators are the cornerstone of prevention but do not eliminate arrhythmia recurrences or reduce the arrhythmogenic substrate. Catheter ablation has emerged as a potential adjunctive therapy to reduce VA burden and implantable cardioverter-defibrillator (ICD) interventions in patients with SHD. This meta-analysis aimed to evaluate the incremental benefits of catheter ablation compared to antiarrhythmic drug (AAD) therapy or standard care in patients with SHD undergoing ICD implantation for VAs. Methods: A systematic search was conducted till April 2025 across PubMed/MEDLINE, Cochrane, google scholar and science direct following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies included patients with SHD receiving ICD therapy, comparing catheter ablation with any alternative treatment. Outcomes assessed included mortality, arrhythmia recurrence, disease burden, and ICD interventions. Statistical analysis was performed using Review Manager, calculating odds ratios (ORs) and 95% confidence intervals (CI), with heterogeneity assessed via I 2 statistics. Results: Eight studies were included, encompassing 536 patients in the catheter ablation group and 560 patients in the control group. Catheter ablation did not significantly reduce all-cause mortality (OR = 0.79, 95% CI: 0.48–1.29, P = .34), cardiovascular mortality (OR = 0.73, 95% CI: 0.37–1.43, P = .36), or death (OR = 0.86, 95% CI: 0.53–1.38, P = .52). However, catheter ablation was associated with a significant reduction in recurrent ventricular tachycardia (VT) (OR = 0.42, 95% CI: 0.27–0.64, P < .001) and cardiac hospitalization (OR = 0.55, 95% CI: 0.34–0.89, P = .015). No significant differences were observed for VT storm or electrical storm. Importantly, catheter ablation significantly reduced inappropriate ICD shocks (OR = 0.36, 95% CI: 0.20–0.66, P < .001), while rates of appropriate ICD shocks and antitachycardia pacing were similar between groups. Conclusion: Catheter ablation offers significant benefits in reducing arrhythmia burden and inappropriate ICD shocks but does not impact overall mortality compared to antiarrhythmic therapy in patients with SHD undergoing ICD implantation.

Background: Non-small cell lung cancer (NSCLC), particularly in advanced stages, has poor prognosis. The main objective of the study is to evaluate real-world treatment outcomes in advanced NSCLC patients harboring an EGFR mutation and being treated with TKIs. Methods: The EGFR mutation status was ascertained by next-generation sequencing. The observational cohort study used prospectively maintained registry data. Patient data were collected at two high-volume institutions in Austria between November 2020 and February 2025. The prevalence of EGFR mutations was 11% (145 out of 1267 patients). Results: Among 53 patients (stage IIIB or higher) with an EGFR mutation, median overall survival (OS) and median progression-free survival (PFS) were 17.7 months (95% CI: 10.4–24.9) and 14.2 months (95% CI: 7.4–20.9), respectively. A total of 36 patients harbored common EGFR mutations (exon 19 deletion or L858R point mutation) and exhibited a significantly better OS than those with an uncommon EGFR genotype (p < 0.005). Patients with exon 19 deletion (n = 25) showed the longest mOS, followed by those with L858R mutation (32.5 vs. 17 months). In multivariable analysis, the EGFR common mutation subtype (HR = 3.71 95%CI: 1.23–11.2) was associated with better OS. Patients with common EGFR genotypes, especially exon 19 deletion obtained longer OS and PFS compared with those with uncommon mutations in exon 18–21. Conclusions: The results underscore the prognostic role of distinct EGFR genotypes and the urgency of determining the mutation status in non-small cell lung cancer patients to ensure the best treatment decision. The study also highlights the challenges regarding to EGFR uncommon mutations and the resulting need for further research to investigate alternative treatment options.

We report a case of massive bleeding from proton pump inhibitor (PPI)‐induced fundic gland polyps (FGPs) that regressed after switching to a histamine‐2 receptor antagonist (H2RA). A 46‐year‐old man with antiphospholipid syndrome had been receiving warfarin and lansoprazole for 4 years. Esophagogastroduodenoscopy (EGD) revealed multiple enlarged, edematous FGPs compared to those observed 3 years earlier. One month later, the patient presented with melena, anemia, and transient loss of consciousness. Laboratory data revealed anemia and a prolonged prothrombin time/international normalized ratio (PT‐INR). Emergency EGD showed refractory oozing from the FGPs caused by insufflation and water jet stimulation. The bleeding was successfully controlled with vitamin K administration. After PT‐INR normalization, no further bleeding occurred, and a follow‐up EGD 3 days later showed no bleeding recurrence. We considered that PPI therapy might lead to recurrent bleeding from the FGPs and switched therapy to an H2RA. Follow‐up EGD at 2 and 6 months revealed gradual and marked regression of the FGPs. This case demonstrates that PPI‐induced FGPs can result in massive bleeding, particularly in patients receiving anticoagulant therapy. Furthermore, FGP regression following the switch to H2RA suggests that H2RA therapy may be an alternative treatment when discontinuation of PPI therapy is not feasible.

The primary indication for ERAT is acute uncomplicated appendicitis; however, in recent years, the successful treatment of appendiceal abscesses in adults has been reported in several cases. Further investigations are warranted to establish the feasibility of ERAT for the management of appendiceal abscesses. This study aimed to evaluate the efficacy and safety of endoscopic retrograde appendicitis therapy (ERAT) for the treatment of acute periappendiceal abscess in adults. This retrospective study included 30 adult patients with acute periappendiceal abscess who underwent ERAT at the Digestive Center of Suining Central Hospital between July 2021 and March 2025. The success rate (technical and clinical), procedure time, intervention time, visual analog scale (VAS) score, length of hospital stay, complications, and absorption condition of the abscesses 3months after the procedure were recorded and analyzed. The technical success rate of ERAT was 80%, and the clinical success rate was 83.3%. The median procedure time was 14.5 (interquartile range [IQR], 11.8-16.5) minutes. The median ERAT intervention duration was 7.0 (IQR, 4.8-10.0) days. The postoperative VAS score was significantly decreased (P < 0.001), and the average length of hospital stay was 6.7 ± 2.4days. Three months after the procedure, the abscesses were completely absorbed in 87.0% of the patients and partially absorbed in 13.0% of the patients. Two patients developed postoperative complications, namely, abscess dissemination and transient high fever. In adult patients with acute periappendiceal abscess, ERAT may be an alternative and effective treatment option in the early stage.

Aminoglycosides have long been considered essential agents in P. aeruginosa chemotherapy; however, resistance is on the rise. Glutamate is a crucial molecule for all living organisms, serving a fundamental function in various metabolic activities. A deeper comprehension of metabolic flux may facilitate effective therapeutic strategies for the eradication of antibiotic-resistant microorganisms. In this work, we aim to investigate a novel approach of amino acid-antibiotic adjuvant to potentiate activity of existing therapeutics through a low-toxicity adjuvant strategy offering lower risk of unwanted effects. We used 25 P. aeruginosa whole-genome sequenced clinical isolates selected from a genomically diverse set of isolates. The effect of glutamate-gentamycin combination on bacterial growth was tested. The effect of gentamycin-glutamate combination on outer membrane permeability was also studied using NPN. GWAS analysis was implemented using Pyseer to investigate genes underlying the observed enhanced effect of glutamate/gentamycin combination on bacterial killing. Among the tested 25 P. aeruginosa isolates, fifteen isolates demonstrated enhanced combinatorial effect of the gentamycin-glutamate combination resulting in enhanced bacterial killing effect. Interestingly observed, a set of genes involved in glycerophospholipid metabolism, purine metabolism, and glutamate metabolic pathways were interconnected showing significant differences among the two phenotypic groups using Pyseer. The uptake of fluorophore NPN in the presence of glutamate and two sub-inhibitory concentrations of gentamycin was increased indicating increased membrane permeabilization. This study reports the enhanced antibacterial effect of gentamycin-glutamate combination against P. aeruginosa opening doors for novel alternative treatment approaches against drug-resistant bacteria. Metabolic reprogramming offers a promising potential to enhance antibiotic mediated bacterial killing.

Clinical CaseIn 2015, a 35-year-old male was referred for preoperative evaluation of pituitary surgery after MRI revealed a 25×25×19 mm macroadenoma compressing the optic chiasm. Initial prolactin was ∼2000 µg/L and IGF-1 was markedly elevated (623 µg/L). During assessment, severe hypercalcemia (>14 mg/dL) was noted with PTH also significantly elevated (up to 623 pg/mL). After correction, subtotal (3.5 gland) parathyroidectomy was performed, confirming multiglandular adenoma. Postoperatively, permanent hypoparathyroidism developed, requiring lifelong calcium and calcitriol. Despite residual macroadenoma, the patient declined pituitary surgery; cabergoline was selected, normalizing prolactin and IGF-1 with radiologic regression.The patient also initially refused thymic surgery despite a mediastinal mass, but underwent thymectomy in 2020. Histopathology revealed a well-differentiated thymic NET, Grade 2, Ki-67 3–4%, with pleural metastases. Laboratory results showed marked hypergastrinemia (417 ng/L), normal glucagon (173 pg/mL), elevated Chromogranin A (850 µg/L) and neuron-specific enolase. Ga-68 PET/CT demonstrated pancreatic, pleural, and mediastinal metastases. MEN1 genetic testing confirmed a pathogenic mutation.The patient underwent thymectomy and subtotal parathyroidectomy. Cabergoline achieved biochemical remission of pituitary disease. Sandostatin LAR (30 mg IM every 28 days) was initiated for hormonal and antiproliferative effects. Calcium and calcitriol continue for hypoparathyroidism. Multidisciplinary follow-up is ongoing.ConclusionThis case illustrates an aggressive MEN1 variant with multihormonal secretion and metastatic thymic NET. Thymic involvement is rare but prognostically significant. Somatostatin analogs are valuable for hormonal and tumor control. In case of non-response, alternative systemic treatment options may also be used. Close, multidisciplinary surveillance is essential for high-risk MEN1 patients.

Aim of study: To investigate the effects of alternate partial root-zone irrigation (AI) on root growth, gene expression, and metabolite accumulation in fragrant pear (Pyrus pyrifolia (Burm. f.) Nakai ‘Yulu’), and explore the underlying mechanisms enhancing water use efficiency (WUE) and regulating the rhizosphere environment. Area of study: The experiment was conducted in a plastic greenhouse at the Fruit Tree Institute of Shanxi Academy of Agricultural Sciences, China. Material and methods: Three irrigation treatments —conventional irrigation (CK), fixed partial root-zone irrigation (FI), and AI— were applied. Morphological, physiological, and WUE indicators were measured. Transcriptomic and metabolomic analyses of pear roots were performed using high-throughput sequencing to identify differentially expressed genes (DEGs) and metabolites. Main results: Alternate partial root-zone irrigation treatment significantly enhanced growth compared to CK, with shoot length, diameter, and net photosynthetic rate (Pn) increasing by 35.25%, 46.09%, and 13.41%, respectively. Significant improvements were also observed in the root-to-shoot ratio, total root length density (RLD), and root surface area density (RSAD). Additionally, WUE increased by 31.87%. Transcriptomic analysis revealed the upregulation of auxin-regulating genes (e.g., SAUR), gibberellin (GA) synthesis genes (e.g., GA20OX2), and aquaporin-related genes, which enhanced the accumulation of GA (e.g., GA44, GA24, GA5) and auxin-related metabolites (e.g., 3-indoleacetonitrile). Alternate partial root-zone irrigation also upregulated stress-responsive genes such as Cinnamoyl CoA reductase (CCR), BSK, and COI1, increasing the accumulation of metabolites like cinnamaldehyde and jasmonoyl-L-isoleucine, which enhanced root growth, plant resistance, and regulated the rhizosphere microbial community. Research highlights: Alternate partial root-zone irrigation promotes root growth in pear trees by upregulating aquaporin genes, hormone pathway-related genes, and stress-resistance genes, while also modulating the rhizosphere environment.

Tobacco dependence poses significant health and economic burdens globally, with over one billion smokers and eight million deaths annually. Current smoking cessation strategies, including pharmacotherapy and behavioral treatments, often have limited efficacy and potential side effects. Acupuncture, a potential alternative treatment, has shown promise in previous studies, but its mechanism and long-term effects on craving remain unclear. This two-center, randomized, controlled clinical trial will enroll 192 patients with moderate to severe tobacco dependence and randomly assign them to Acupuncture, sham-Acupuncture, or basic smoking cessation intervention groups in a 1:1:1 ratio. Blinding will be performed on participants in the Acupuncture, sham-Acupuncture groups and statistical analysts. The 12-week trial will involve 8 weeks of treatment and 4 weeks of follow-up. The primary outcome is abstinence rate at week 8. Secondary outcomes include assessment with the following instruments: craving levels via the Visual Analog Scale and Tobacco Craving Questionnaire, withdrawal symptoms via the Minnesota Withdrawal Scale, working memory via the Sternberg paradigm, and response inhibition ability via the Go/NoGo task. Adverse events will be recorded. The study will adhere to SPIRIT guidelines. This trial will investigate the efficacy of acupuncture for tobacco dependence by including a sham control and examining long-term craving effects. Findings will contribute to understanding the potential of acupuncture as a safe and effective treatment option for tobacco dependence. This trial was registered on the International Traditional Medicine Clinical Trial Registry (Registration number: ITMCTR2024000817) on November 18, 2024.

Interventional oncology has gained a lot of traction as an attractive alternative treatment for various musculoskeletal tumors by offering minimally invasive image-guided therapies. In this domain, thermal ablation is increasingly being used malignant tumors, including bone metastatic disease. Thermal ablation therapies such as radiofrequency ablation, microwave ablation, cryoablation and high intensity focused ultrasound therapy achieve excellent local tumor control and pain palliation, whilst structural stability is ensured through the combination with bone augmentation techniques such as standard or reinforced osteoplasty. Many factors are affecting the results including the biology of the disease the treatment intent (curative or palliative) as well as the potential for complications, like thermal injury to surrounding tissues, highlight the need for meticulous procedural planning. This review highlights the pathophysiology, the current repertoire of thermal ablation techniques, clinical outcomes and the future directions for the treatment of metastatic bone disease.

Surgery is the primary therapy for hard palate cancer, but this sometime worsens oral function and unavailable for patients with several comorbidities. Radiotherapy represents an alternative curative treatment option to preserve oral function, however, there are few reports on the use of radiotherapy for squamous cell carcinoma of the hard palate (SCCHP). High-dose-rate (HDR) brachytherapy has been known as an effective treatment for SCCHP, which seems to be less invasive when mold technique is used. In our hospital, the HDR customized mold brachytherapy (HDR- customized MBT) is available for patients with SCCHP. This study aimed to report the efficacy and toxicity of HDR- customized MBT for patients with early-stage SCCHP. Four patients with early-stage SCCHP were treated with mainly HDR- customized MBT between June 2015 and May 2023. Three of four patients received the combined radiotherapy: one patient underwent short-term external beam radiotherapy (EBRT) before the HDR- customized MBT; two patients underwent single-fraction interstitial brachytherapy before HDR- customized MBT. The total biological effective dose was 77-110Gy (α/β = 10). All patients completed HDR- customized MBT with or without the combined radiotherapy and experienced no local recurrence. The acute toxicity was only mucositis limited to the irradiated area: one case with EBRT developed grade 2 mucositis. Only this case had late grade 2 mucositis; no late adverse events were observed in the other cases. No oral dysfunction or cosmetic problems occurred in any of the patients. This study might show that HDR-customized MBT is useful for early-stage SCCHP and might be an alternative curative treatment option for them to preserve oral function.

The in-vial microextraction technique is emerging as an alternative sample treatment, as it integrates sorbent preparation, adsorption, and desorption of analytes in a single device before instrumental analysis. In this work, the applicability of polycaprolactone polymeric film, recently used for the in-vial microextraction of sex hormones from environmental waters, is studied in a low-capacity format for unconjugated sex hormones determination in biological samples by HPLC-MS/MS. Its performance was evaluated in urine and serum, achieving extraction in a short time (10 and 30 min, in turn) and satisfactory elution with ethanol, with recovery in the range of 65–111% in urine, 55–122% in bovine serum albumin (BSA) solution, and 66–121% in fetal bovine serum (FBS). In the case of protein matrices, a dilution to 20 g L−1 protein content and washing step (3 × 1 mL ultrapure water) afore the elution are required to achieve clean extract, as verified by a Bradford assay. Matrix-matched calibration was used for quantification, obtaining correlation coefficients greater than 0.9929; limits of detection and quantification were in the range of 0.01–0.65 and 0.03–1.96 ng mL−1 in urine, 0.02–0.8 and 0.05–2.5 ng mL−1 in BSA, and 0.02–1.0 and 0.06–3.0 g mL−1 in FBS, respectively. The in-vial polycaprolactone film proved to be reusable for several cycles (up to ten), and the greenness assessment revealed a good adhesion to green sample preparation principles. All these achievements further strengthen its feasibility for efficient extraction/clean-up of trace sex hormones in complex biological samples.

To assess the relationship between the condyle and fossa in idiopathic condylar resorption (ICR) patients with severe Class II skeletal deformities who achieved stable functional and esthetic outcomes. ICR patients receiving orthodontic-orthognathic treatment with more than 2 years of follow-up were included in this retrospective study. Post-treatment changes in Y-axis-B of less than 2 mm were considered indicative of achieving a stable treatment outcome. Anterior joint space (AJS), superior joint space (SJS), and posterior joint space (PJS) on computed tomography (CT) and magnetic resonance images (MRI) were measured. After screening, a total of 20 patients with 40 condyles were included. 12 patients were included in the Stable group and eight patients were included in the Relapse group. In the Stable group, mean AJS, SJS, and PJS linear measurements during follow-up on CT images were 1.82 ± 0.34, 1.78 ± 0.38, and 1.81 ± 0.33 mm, respectively. Ratio of AJS:SJS:PJS was 1.0:0.97:1.0. Mean AJS, SJS, and PJS linear measurements on MRI images were 1.71 ± 0.50, 1.82 ± 0.50, and 1.70 ± 0.51 mm, respectively. Ratio of AJS:SJS:PJS was 1.0:1.06:1.0. In the Relapse group, no constant ratio of joint spaces was found on CT or MRI images. A relationship exists between the condyle and fossa in ICR patients with stable treatment outcomes, as the AJS:SJS:PJS ratio was close to 1:1:1. This condyle-fossa relationship provides clinicians with an assessment criterion and may be an alternative treatment goal for patients with ICR.

To systematically evaluate the comparative efficacy and safety of hyperthermic intravesical chemotherapy (HIVEC) versus bacillus Calmette-Guérin (BCG) instillation in patients with non-muscle-invasive bladder cancer (NMIBC). A systematic literature search was conducted across PubMed, Embase, the Cochrane Library, and CBM from inception to June 30, 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251075299. Randomized controlled trials and cohort studies comparing HIVEC with BCG in NMIBC patients were included. Primary outcomes were 24-month recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). Secondary outcomes included adverse events. Risk ratios (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using fixed- or random-effects models. Seven studies involving 820 patients were included. The meta-analysis showed no significant differences between HIVEC and BCG in 24-month RFS (RR = 1.01, 95% CI: 0.90-1.12), PFS (RR = 1.00, 95% CI: 0.95-1.05), or OS (RR = 0.99, 95% CI: 0.91-1.09). However, BCG was associated with a significantly higher incidence of dysuria (RR = 1.38, 95% CI: 0.57-3.37). No significant differences were observed in other adverse events such as urinary tract infection, hematuria, or pain. HIVEC demonstrates comparable oncological efficacy to BCG in terms of 24-month RFS, PFS, and OS for NMIBC patients, while offering a better tolerability profile with a significantly lower risk of dysuria. These findings support HIVEC as a valuable alternative treatment option, particularly in the context of BCG shortages or for BCG-intolerant patients.

BackgroundU.S. Syphilis cases are rising, including in Florida. Benzathine Penicillin (BP) is the preferred treatment of syphilis with a clinical success rate of 90-100%. Doxycycline (Doxy) remains an alternative treatment option, with a 83-100% rate of clinical success. The Tampa VA Medical Center faced a national BP shortage beginning in April 2023 due to manufacturer delays and rising treatment need. Although the FDA temporarily allowed importation and use of benzathine benzylpenicillin (Extencilline™), federal health care facilities continued faced procurement restrictions, and BP was rationed. Oral doxy 100 mg orally twice daily became our preferred syphilis treatment for 14 months.Figure 1Patient Clinical Response based on Syphilis TreatmentFigure 2Clinical Success in the Full CohortMethodsWe retrospectively reviewed all veterans treated for syphilis at our center between 1/1/23 and 12/31/24. Cases identified had a positive nontreponemal test and an elevated rapid plasma reagin (RPR) titer of ≥ 1:1. If RPR positive, a > 4x rise in the RPR titer met criteria for retreatment. Sixty-two patients (pts) met criteria. Data collected included date/value of RPR titer, syphilis stage, regimen used, HIV status, and treatment response as defined as a > 4x reduction in titer.Figure 3Clinical Success in Patients with HIVResultsOf 62 pts, there were 32 pts w/syphilis < 1 yr, and 28 pts w/syphilis > 1yr, and 2 pts with neurosyphilis (NS) (Fig. 1). The Doxy x 14 days success rate was 93% and the BP 2.4 million units (MU) success rate was 100%. One patient received Doxy x 14 days and was retreated x 28 days due to noncompliance. The success rate for Doxy x 28 days was 92% and for BP 7.2 MU was 100%. One patient in the BP 2.4 MU group, 2 in the BP 7.2 MU group, 3 in the Doxy x 28-day group, and 1 NS patient did not follow up (Fig. 1). HIV positivity was 28.6%. Overall, clinical success rates exceeded 90% for Doxy x 14 days and Doxy x 28 days in comparison to BP 2.4 MU and BP 7.2 MU, respectively (Fig. 2). The clinical success rate in the HIV subpopulation for the Doxy x14, Doxy x28, and BP 2.4 MU group was 100%. One HIV patient was lost to follow-up in the BP 7.2 MU group and in the NS group (Fig. 3).ConclusionIn veterans with syphilis, responses were similar in both the Doxy and BP groups during the review period, with both achieving greater than 90% clinical success, including in an HIV+ cohort. In the face of Penicillin supply chain irregularities, Doxy remains a highly effective alternative to BP.DisclosuresAll Authors: No reported disclosures

BackgroundAmikacin liposome inhalation suspension (ALIS), a nebulized formulation of amikacin, is the first treatment approved in the United States, as part of a combination therapy, for adults with refractory Mycobacterium avium complex lung disease (MAC-LD) who have limited or no alternative treatment options. In clinical studies, ALIS treatment was associated with adverse events (AEs) of mild or moderate severity which led to treatment discontinuation in up to 24.4% of patients. In clinical practice, inadequate management of AEs may lead to decreased treatment adherence and early discontinuation.An expert steering committee (SC) convened to establish practice-based, and expert-agreed recommendations for the mitigation strategies of ALIS-related AEs for patients with MAC-LD, with the aim of providing up-to-date practical recommendations for healthcare professionals.MethodsThe SC included: 7 pulmonologists, 2 infectious disease specialists, 1 otolaryngologist, 1 nurse practitioner, and 1 patient advocate. The SC aligned on clinical topics and identified critical unanswered questions. Recommendations were drafted to address each question based on a comprehensive literature review and clinical experience with patients. Consensus on recommendations for each statement was achieved via modified Delphi methodology voting on a 9-point scale.ResultsThe SC identified the following clinical topics: preparing the patient before the start of treatment; preventing AEs; monitoring AEs; mitigating AEs and incorporating the assistance of a multidisciplinary team. Due to the paucity of publications, most recommendations are expert-opinion based.ConclusionThe SC made recommendations based on literature, healthcare experience, and patient perspectives for the management of ALIS-associated AEs. A standardized team approach and involvement of a multidisciplinary team, including pulmonologists, infectious disease specialists and otolaryngologists, may help facilitate adherence to treatment. It is expected that successful recognition and management of AEs will be aided by educating patients and caregivers, and informed members of the clinical care team before and during ALIS treatment.This initiative was funded by Insmed Inc. with no input on the recommendations.DisclosuresColin Swenson, MD, Insmed Inc.: Advisor/Consultant Charles L. Daley, MD, AN2: Advisor/Consultant|AN2: Grant/Research Support|Bill and Melinda Gates Foundation: Advisor/Consultant|Bugworks: Grant/Research Support|Galapagos: Advisor/Consultant|Grifols: Advisor/Consultant|Hyfe: Advisor/Consultant|Insmed Inc.: Advisor/Consultant|Insmed Inc.: Grant/Research Support|Juvabis: Grant/Research Support|MannKind: Advisor/Consultant|MannKind: Grant/Research Support|Matinas BioPharma Holdings, Inc.: Advisor/Consultant|Monaghan: Advisor/Consultant|Nob Hill: Advisor/Consultant|Ostuka Pharmaceutical: Advisor/Consultant|Paratek Pharmaceuticals: Advisor/Consultant|Paratek Pharmaceuticals: Grant/Research Support|Shionogi: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant|Spero Therapeutics: Grant/Research Support Jennifer Faber-Gerling, NP, Insmed Inc.: Advisor/Consultant Patrick A. Flume, MD, Insmed Inc.: Advisor/Consultant|Insmed Inc.: Grant/Research Support Shannon H. Kasperbauer, MD, AN2: Advisor/Consultant|COPD Foundation: Advisor/Consultant|Insmed Inc.: Advisor/Consultant|Paratek: Advisor/Consultant|Zambon: Advisor/Consultant H. Jeffrey Kim, MD, Insmed Inc.: Advisor/Consultant Amy Leitman, N/A, MicuRx: Advisor/Consultant Theodore K. Marras, MD, Insmed Inc.: Advisor/Consultant|Mannkind Corp: Advisor/Consultant|Partner Therapeutics: Advisor/Consultant Kenneth N. Olivier, MD, Insmed. Inc: Advisor/Consultant|Mannkind Corporation: Advisor/Consultant|Paratek Pharma: Advisor/Consultant|Paratek Pharma: Site PI|ReCode Therapeutics: Grant/Research Support|Spero Therapeutics: Advisor/Consultant|Spero Therapeutics: Site PI|Verona Pharma: Site PI Kevin L. Winthrop, MD, MPH, Insmed Inc.: Grant/Research Support Juzar Ali, MD; FRCP(C); FCCP , EuroImmun: Honoraria|Insmed Inc.: Advisor/Consultant

4-Methyl-5-Acetylthiazole (Q11), a novel CYP2E1 inhibitor, has a protective effect on the hepatotoxicity induced by acetaminophen.

Computer-Aided Design (CAD) combined with 3-dimensional (3D) printing technology has been extensively applied in the treatment of endodontic diseases. The goal of this novel report is to highlight a fully guided autotransplantation with CAD and 3D printing technology for treatment of tooth fracture. The maxillary left first molar #26 had a vertical fracture that severely affected occlusion and life quality of the patient. Clinical examination showed an oblique crack across the mesiobuccal cusp and the distopalatal cusp of #26, cone-beam computed tomography (CBCT) showed a vertical fracture line reaching the floor of pulp chamber, a subtle increase in the palatal periodontal ligament space, and hypodensity in the distobuccal apex area. Due to the strong desire to preserve natural tooth and financial considerations, the patient declined conventional prosthetic restoration and chose autotransplantation of mandibular left third molar #38 to the site of #26. A 3D printed guide was used to precisely prepare the extraction socket, facilitating the immediate and accurate autotransplantation of #38 into the site of #26. Root canal therapy was performed 3 weeks after surgery. During the 3-year follow-up, the patient could chew normally without any discomfortable feelings, X-ray radiographs showed a significant increase in bone density around the root and a superior periodontal ligament healing without root resorption. For patients who do not choose prosthetic restoration due to socio-economic conditions, we propose tooth autotransplantation as an alternative treatment for tooth fractures under the help of modern CAD and 3D printing technology.