Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

Timely delivery of PORT for head and neck squamous cell carcinoma in a county hospital.

Objectives: The objective of this study was to compare the rate of post-operative radiation therapy (PORT) initiation within 6 weeks for head and neck squamous cell carcinoma patients treated at a safety net, academic institutio between 2019 and 2021 versus those treated in 2022 after implementation of a new clinical pathway. Methods: A retrospective case-control study was performed at a single tertiary care, safety-net, academic institution. Patient demographics, tumor characteristics, dates of surgery, and other treatment dates were collected from the electronic medical record. The time from surgery to PORT was calculated. Patients who started radiation treatment within 42 days of surgery were regarded as having started PORT on time. The demographics, tumor characteristics, and rate of timely PORT for the two cohorts of patients were compared. Results: From 2018 to 2021, our rate of PORT initiation within 6 weeks of surgery was 12% (n = 57). In 2022, our rate of timely PORT was 88% (n = 16), p < 0.5. Patient demographics and characteristics were similar with the exception of marital status and use of free-flap reconstruction. The 2022 cohort was more likely to be single (p < 0.5), and all patients underwent free-flap reconstruction in 2022 (p < 0.05). Conclusion: Early referrals, frequent communication, and use of a secure registry were the key to the success found by our group despite the socioeconomic challenges of our underserved, safety-net hospital patient population. The changes made at our institution should serve as a template for other institutions seeking to improve the quality of care for their HNSCC patients.

Gelatin methacrylate hydrogels culture model for glioblastoma cells enriches for mesenchymal-like state and models interactions with immune cells.

Glioblastoma is the most lethal primary malignant brain tumor in adults. Simplified two-dimensional (2D) cell culture and neurospheres in vitro models fail to recapitulate the complexity of the tumor microenvironment, limiting its ability to predict therapeutic response. Three-dimensional (3D) scaffold-based models have emerged as a promising alternative for addressing these concerns. One such 3D system is gelatin methacrylate (GelMA) hydrogels, and we aimed to understand the suitability of using this system to mimic treatment-resistant glioblastoma cells that reside in specific niches. We characterized the phenotype of patient-derived glioma cells cultured in GelMA hydrogels (3D-GMH) for their tumorigenic properties using invasion and chemoresponse assays. In addition, we used integrated single-cell and spatial transcriptome analysis to compare cells cultured in 3D-GMH to neoplastic cells in vivo. Finally, we assessed tumor-immune cell interactions with a macrophage infiltration assay and a cytokine array. We show that the 3D-GMH system enriches treatment-resistant mesenchymal cells that are not represented in neurosphere cultures. Cells cultured in 3D-GMH resemble a mesenchymal-like cellular phenotype found in perivascular and hypoxic regions and recruit macrophages by secreting cytokines, a hallmark of the mesenchymal phenotype. Our 3D-GMH model effectively mimics the phenotype of glioma cells that are found in the perivascular and hypoxic niches of the glioblastoma core in situ, in contrast to the neurosphere cultures that enrich cells of the infiltrative edge of the tumor. This contrast highlights the need for due diligence in selecting an appropriate model when designing a study's objectives.

Evaluating Treatment Patterns for Small Cell Carcinoma of the Colon Using the National Cancer Database (NCDB).

OBJECTIVE(S): The objective of this study was to characterize the clinicopathological prognostic factors and treatment patterns for small cell carcinoma (SCC) of the colon, a rare disease without standard treatment guidelines. METHODS: We analyzed clinicopathological and treatment variables for 503 cases of histologically proven SCC colon entered into the National Cancer Database (NCDB) between 2004 and 2013. Survival curves were generated using Kaplan-Meier and compared by the log-rank test. Cox proportional hazard regression was used to control for covariates and evaluate the effect of different treatment modalities on overall survival. RESULTS: Four hundred seventy-two (93.8%) patients had complete clinical staging information and were therefore included in our analysis. Of these patients, 149 (31.5%) had limited stage disease (LD) and 323 (68.4%) had extensive stage disease (ED) at presentation. Median overall survival (OS) for patients with ED was significantly lower than for those with LD (4.04 months vs. 21.82 months; p < 0.001). Multivariate Cox regression analysis showed administration of chemotherapy was associated with improved survival in patients with LD and ED (p = 0.026, p < 0.001) while surgery was not associated with improved survival in patients with LD or ED (p = 0.943, p = 0.630). Radiation therapy was associated with improved survival in patients with ED (p = 0.044). CONCLUSIONS: SCC of the colon carries a poor prognosis, especially in patients presenting with metastatic disease. Surgery and chemotherapy are administered more frequently than radiation, and chemotherapy is associated with improved survival, unlike surgery.

Gold nanoparticle-based rapid detection and isolation of cells using ligand-receptor chemistry.

Identification and isolation of low-frequency cells of interest from a heterogeneous cell mixture is an important aspect of many diagnostic applications (including enumeration of circulating tumor cells) and is integral to various assays in (cancer) biology. Current techniques typically require expensive instrumentation and are not amenable to high throughput. Here, we demonstrate a simple and effective platform for cell detection and isolation using gold nanoparticles (Au NPs) conjugated with hyaluronic acid (HA) i.e. Au-PEG-HA NPs. The proposed platform exploits ligand-receptor chemistry to detect/isolate cells with high specificity and efficiency. When the Au-PEG-HA NPs come in contact with cells that express CD44 (the receptor for HA), a clear colorimetric change occurs (along with an accompanying SPR peak shift from 521 nm to 559 nm) in the solution due to NPs-cell interaction. This clearly discernible, colorimetric change can be leveraged by point-of-care devices employed in diagnostic applications. Finally, we show that we can successfully isolate viable cells from a heterogeneous cell population (including from human blood samples) with high specificity, which can be used in further downstream applications. The developed NPs-based platform can be a convenient and cost-efficient alternative for diagnostic applications and for cell isolation or sorting in research laboratories.

Predicting acute contact toxicity of pesticides in honeybees (Apis mellifera) through a k-nearest neighbor model.

Ecological risk assessment of plant protection products (PPPs) requires an understanding of both the toxicity and the extent of exposure to assess risks for a range of taxa of ecological importance including target and non-target species. Non-target species such as honey bees (Apis mellifera), solitary bees and bumble bees are of utmost importance because of their vital ecological services as pollinators of wild plants and crops. To improve risk assessment of PPPs in bee species, computational models predicting the acute and chronic toxicity of a range of PPPs and contaminants can play a major role in providing structural and physico-chemical properties for the prioritisation of compounds of concern and future risk assessments. Over the last three decades, scientific advisory bodies and the research community have developed toxicological databases and quantitative structure-activity relationship (QSAR) models that are proving invaluable to predict toxicity using historical data and reduce animal testing. This paper describes the development and validation of a k-Nearest Neighbor (k-NN) model using in-house software for the prediction of acute contact toxicity of pesticides on honey bees. Acute contact toxicity data were collected from different sources for 256 pesticides, which were divided into training and test sets. The k-NN models were validated with good prediction, with an accuracy of 70% for all compounds and of 65% for highly toxic compounds, suggesting that they might reliably predict the toxicity of structurally diverse pesticides and could be used to screen and prioritise new pesticides.

Gelatin Methacrylate Hydrogels as Biomimetic Three-Dimensional Matrixes for Modeling Breast Cancer Invasion and Chemoresponse in Vitro.

Recent studies have shown that three-dimensional (3D) culture environments allow the study of cellular responses in a setting that more closely resembles the in vivo milieu. In this context, hydrogels have become popular scaffold options for the 3D cell culture. Because the mechanical and biochemical properties of culture matrixes influence crucial cell behavior, selecting a suitable matrix for replicating in vivo cellular phenotype in vitro is essential for understanding disease progression. Gelatin methacrylate (GelMA) hydrogels have been the focus of much attention because of their inherent bioactivity, favorable hydration and diffusion properties, and ease-of-tailoring of their physicochemical characteristics. Therefore, in this study we examined the efficacy of GelMA hydrogels as a suitable platform to model specific attributes of breast cancer. We observed increased invasiveness in vitro and increased tumorigenic ability in vivo in breast cancer cells cultured on GelMA hydrogels. Further, cells cultured on GelMA matrixes were more resistant to paclitaxel treatment, as shown by the results of cell-cycle analysis and gene expression. This study, therefore, validates GelMA hydrogels as inexpensive, cell-responsive 3D platforms for modeling key characteristics associated with breast cancer metastasis, in vitro.

Amphiphilic, hydrophilic, or hydrophobic synthetic bacteriochlorins in biohybrid light-harvesting architectures: consideration of molecular designs.

Biohybrid light-harvesting architectures can be constructed that employ native-like bacterial photosynthetic antenna peptides as a scaffold to which synthetic chromophores are attached to augment overall spectral coverage. Synthetic bacteriochlorins are attractive to enhance capture of solar radiation in the photon-rich near-infrared spectral region. The effect of the polarity of the bacteriochlorin substituents on the antenna self-assembly process was explored by the preparation of a bacteriochlorin-peptide conjugate using a synthetic amphiphilic bacteriochlorin (B1) to complement prior studies using hydrophilic (B2, four carboxylic acids) or hydrophobic (B3) bacteriochlorins. The amphiphilic bioconjugatable bacteriochlorin B1 with a polar ammonium-terminated tail was synthesized by sequential Pd-mediated reactions of a 3,13-dibromo-5-methoxybacteriochlorin. Each bacteriochlorin bears a maleimido-terminated tether for attachment to a cysteine-containing analog of the Rhodobacter sphaeroides antenna ß-peptide to give conjugates ß-B1, ß-B2, and ß-B3. Given the hydrophobic nature of the ß-peptide, the polarity of B1 and B2 facilitated purification of the respective conjugate compared to the hydrophobic B3. Bacteriochlorophyll a (BChl a) associates with each conjugate in aqueous micellar media to form a dyad containing two ß-peptides, two covalently attached synthetic bacteriochlorins, and a datively bonded BChl-a pair, albeit to a limited extent for ß-B2. The reversible assembly/disassembly of dyad (ß-B2/BChl)2 was examined in aqueous detergent (octyl glucoside) solution by temperature variation (15-35 °C). The energy-transfer efficiency from the synthetic bacteriochlorin to the BChl-a dimer was found to be 0.85 for (ß-B1/BChl)2, 0.40 for (ß-B2/BChl)2, and 0.85 for (ß-B3/BChl)2. Thus, in terms of handling, assembly and energy-transfer efficiency taken together, the amphiphilic design examined herein is more attractive than the prior hydrophilic or hydrophobic designs.

Ibrutinib for B cell malignancies.

Research over the role of Bruton's agammaglobulinemia tyrosine kinase (BTK) in B-lymphocyte development, differentiation, signaling and survival has led to better understanding of the pathogenesis of B-cell malignancies. Down-regulation of BTK activity is an attractive novel strategy for treating patients with B-cell malignancies. Ibrutinib (PCI-32765), a potent inhibitor of BTK induces impressive responses in B-cell malignancies through irreversible bond with cysteine-481 in the active site of BTK (TH/SH1 domain) and inhibits BTK phosphorylation on Tyr223. This review discussed in details the role of BTK in B-cell signaling, molecular interactions between B cell lymphoma/leukemia cells and their microenvironment. Clinical trials of the novel BTK inhibitor, ibrutinib (PCI-32765), in B cell malignancies were summarized.

Hydrophilic tetracarboxy bacteriochlorins for photonics applications.

Bacteriochlorins absorb strongly in the near-infrared (NIR, 700-900 nm) region and hence are well suited for photophysical studies and photomedical applications, yet such endeavors heretofore have been largely limited by the intrinsic lipophilicity of the bacteriochlorin macrocycle. Here, a new molecular design is investigated wherein 3,5-dicarboxyphenyl units are appended to the ß-pyrrolic positions of the bacteriochlorin. Use of the 3,5-aryl substitution motif places the carboxylic acid groups, which are anionic at neutral pH, above and below the plane of the bacteriochlorin macrocycle. A de novo synthesis has been employed to create five such bacteriochlorins, which uses as intermediates two new 2,12-dibromobacteriochlorin building blocks and a known 3,13-dibromobacteriochlorin. The aryl groups with protected carboxylate moieties were introduced by Suzuki coupling; subsequent deprotection afforded the hydrophilic bacteriochlorins. The latter were characterized by absorption and fluorescence spectroscopy in DMF and in aqueous phosphate buffer (pH 7). In most cases, comparable sharp emission (FWHM of ∼25 nm) and modest fluorescence yields (0.060-0.11) were observed in aqueous phosphate buffer medium and in DMF. Aqueous solubility was examined by absorption spectral interrogation of samples over a 1000-fold concentration range with reciprocal change in pathlength (∼0.5, 5, 50, and 500 µM; 10, 1, 0.1, and 0.01 cm pathlength cuvettes). One hydrophilic bacteriochlorin was prepared that contains a single maleimido-terminated tether for bioconjugation; the tether was installed by the sequence of 15-bromination of the bacteriochlorin, Suzuki coupling, and DCC-mediated amide formation. The maleimido-bacteriochlorin was conjugated to a 48-residue cysteine-containing peptide analogue of a constituent from a bacterial photosynthetic light-harvesting complex. Taken together, the results show a new molecular design and facile de novo synthetic route for obtaining hydrophilic bacteriochlorins including a bioconjugatable group if desired.

Emergence of integrated urology-radiation oncology practices in the State of Texas.

PURPOSE: Integrated urology-radiation oncology (RO) practices have been advocated as a means to improve community-based prostate cancer care by joining urologic and radiation care in a single-practice environment. However, little is known regarding the scope and actual physical integration of such practices. We sought to characterize the emergence of such practices in Texas, their extent of physical integration, and their potential effect on patient travel times for radiation therapy. METHODS AND MATERIALS: A telephone survey identified integrated urology-RO practices, defined as practices owned by urologists that offer RO services. Geographic information software was used to determine the proximity of integrated urology-RO clinic sites with respect to the state's population. We calculated patient travel time and distance from each integrated urology-RO clinic offering urologic services to the RO treatment facility owned by the integrated practice and to the nearest nonintegrated (independent) RO facility. We compared these times and distances using the Wilcoxon-Mann-Whitney test. RESULTS: Of 229 urology practices identified, 12 (5%) offered integrated RO services, and 182 (28%) of 640 Texas urologists worked in such practices. Approximately 53% of the state population resides within 10 miles of an integrated urology-RO clinic site. Patients with a diagnosis of prostate cancer at an integrated urology-RO clinic site travel a mean of 19.7 miles (26.1 min) from the clinic to reach the RO facility owned by the integrated urology-RO practice vs 5.9 miles (9.2 min) to reach the nearest nonintegrated RO facility (P<.001). CONCLUSIONS: Integrated urology-RO practices are common in Texas and are generally clustered in urban areas. In most integrated practices, the urology clinics and the integrated RO facilities are not at the same location, and driving times and distances from the clinic to the integrated RO facility exceed those from the clinic to the nearest nonintegrated RO facility.

Dentistry and the myasthenia gravis patient: a review of the current state of the art.

Myasthenia gravis (MG) is a chronic neuromuscular disease characterized by muscular weakness and fatigability. Dental management of patients diagnosed with MG presents a challenge to the oral health care provider. The purpose of this article was to review the etiology, pathogenesis, diagnosis, and clinical signs and symptoms associated with MG, highlighting the role of the oral health care provider in the process of diagnosis and management of the oral and dental complications that might be associated with the disease, while avoiding myasthenic crisis. A discussion of the recent approaches to treatment of the disease and current research on MG is presented.

Role of in silico genotoxicity tools in the regulatory assessment of pharmaceutical impurities.

The toxicological assessment of genotoxic impurities is important in the regulatory framework for pharmaceuticals. In this context, the application of promising computational methods (e.g. Quantitative Structure-Activity Relationships (QSARs), Structure-Activity Relationships (SARs) and/or expert systems) for the evaluation of genotoxicity is needed, especially when very limited information on impurities is available. To gain an overview of how computational methods are used internationally in the regulatory assessment of pharmaceutical impurities, the current regulatory documents were reviewed. The software recommended in the guidelines (e.g. MCASE, MC4PC, Derek for Windows) or used practically by various regulatory agencies (e.g. US Food and Drug Administration, US and Danish Environmental Protection Agencies), as well as other existing programs were analysed. Both statistically based and knowledge-based (expert system) tools were analysed. The overall conclusions on the available in silico tools for genotoxicity and carcinogenicity prediction are quite optimistic, and the regulatory application of QSAR methods is constantly growing. For regulatory purposes, it is recommended that predictions of genotoxicity/carcinogenicity should be based on a battery of models, combining high-sensitivity models (low rate of false negatives) with high-specificity ones (low rate of false positives) and in vitro assays in an integrated manner.

A dose-response relationship for time to bone pain resolution after stereotactic body radiotherapy (SBRT) for renal cell carcinoma (RCC) bony metastases.

BACKGROUND: To investigate the utility of stereotactic body radiotherapy (SBRT) in the treatment of painful renal cell carcinoma (RCC) bone metastases, and for a possible dose effect on time to symptom relief. MATERIAL AND METHODS: Eighteen patients with 24 painful osseous lesions from metastatic RCC were treated with SBRT. The most common treatment regimens were 24 Gy in 3 fractions and 40 Gy in 5 fractions. The times from treatment to first reported pain relief and time to symptom recurrence were evaluated. Median follow-up was 38 weeks (1-156 weeks). RESULTS: Seventy-eight percent of all patients had pain relief. Patients treated with a BED > 85 Gy achieved faster and more durable pain relief compared to those treated with a BED < 85 Gy. There was decrease in time to pain relief after a change in treatment regimen to 8 Gy × 5 fractions (BED = 86). There was only one patient with grade 1 skin toxicity. No neurological or other toxicity was observed. CONCLUSIONS: SBRT can safely and effectively treat painful RCC bony metastases. There appears to be a relationship between radiation dose and time to stable pain relief.

Is clonidine an adequate alternative to epinephrine as a vasoconstrictor in patients with hypertension?

PURPOSE: To evaluate the safety and efficacy of an admixture of lidocaine with clonidine with regard to the anesthetic abilities, hemodynamic parameters, and postoperative pain control and to compare the results with those obtained with a lidocaine-epinephrine solution. MATERIALS AND METHODS: A total of 50 patients with poorly controlled, moderate hypertension (American Society of Anesthesiologists class II) who presented for uncomplicated upper third molar extraction were included in a double-blind study. The time of onset of action, duration, and intensity of anesthesia and the vasoconstrictor properties were evaluated. The hemodynamic changes (ie, systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, ST-segment depression of 1 mm or greater, and cardiac arrhythmias) were recorded. The presence of postoperative pain and analgesic requirements were also compared. The results were analyzed using an unpaired, type sample equal-variance t test with the Bonferroni correction. RESULTS: Of the 50 patients with hypertension (American Society of Anesthesiologists class II), 25 received 2 mL of 2% lidocaine with clonidine (15 µg/mL) and 25 received lidocaine with epinephrine (12.5 µg/mL). There were no significant differences between the 2 agents with regard to the time of onset of action, duration or intensity of anesthesia, or the vasoconstrictor properties. The clonidine group showed better hemodynamic parameters compared with the epinephrine group. The clonidine group showed significantly lesser postoperative pain and, therefore, had lesser analgesic consumption. CONCLUSIONS: Clonidine could be a useful and safe alternative to epinephrine for intraoral block anesthesia with lidocaine in patients with hypertension and American Society of Anesthesiologists class II.

Unerupted lower third molars and their influence on fractures of the mandibular angle and condyle.

Our aim was to assess the influence of the presence and state of impaction of mandibular third molars on the incidence of fractures of the mandibular angle and condyle. We designed a retrospective study of patients who presented for the treatment of mandibular fractures from January 2006 to April 2011. The independent variables were the presence and degree of impaction of lower third molars, and the outcome variables were the incidence of fractures of the mandibular angle and condyle. The information was acquired from hospital records and panoramic radiographs. Personal data included age, sex, mechanism of injuries, and number of fractures of the mandibular angle and condyle. We studied 110 fractures of the mandibular condyle and 80 of the angle. The incidence of fractures of the mandibular angle was higher in the group with incompletely erupted third molars (37/80, p<0.001) and that of condylar fractures was higher in the group without (67/110, p<0.001). An incompletely erupted third molar reduces the risk of condylar fractures and increases the risk of fractures of the mandibular angle.

Involvement of the muscle-tendon junction in skeletal muscle atrophy: an ultrastructural study.

BACKGROUND: The muscle-tendon junction (MTJ) is a physiologically vital tissue interface and a highly specialized region in the muscle-tendon unit. It is the weakest point in the muscle-tendon unit, making it susceptible to strain injuries. Nonetheless, knowledge of the pathological changes affecting this region and of its response to the atrophy process is very limited. The aim of the study was to examine MTJ ultrastructural morphology in patients with different conditions that induce skeletal muscle atrophy and to attempt a grading of the atrophy process. MATERIALS AND METHODS: Fifteen patients undergoing amputation in the distal or proximal third of the lower leg due to chronic or acute conditions were divided into two groups. Specimens of gastrocnemius muscle collected at the time of surgery were analyzed by histology and electron microscopy. The contact between muscle and tendon was measured using a dedicated software that calculated semi-automatically the base (B) and perimeter (P) of muscle cell finger-like processes at the MTJ. RESULTS: Electron microscopy. The cells in the atrophic muscle of the chronic group were shallow and bulky. In the acute group, the myotendinous endings differed significantly in their structure from those of the chronic group. In atrophic muscle, the contact between muscle and tendon was reduced by quantitative and qualitative changes in the myotendinous endings. The B/P ratio allowed definition of three grades of myotendinous ending degeneration. DISCUSSION: It is unclear whether degenerative changes induced by immobilization in muscle and, specifically, the MTJ are temporary and reversible or permanent. CONCLUSIONS: This preliminary study suggested a classification of ultrastructural MTJ changes into grade 0, reflecting a quite normal MTJ; grade 1, an intermediate process that might lead to irreversible atrophy or to recovery, spontaneously or with drug therapy; and grade 2, irreversible process with complete structural alteration.

The association of cryoglobulinaemia with sustained virological response in patients with chronic hepatitis C.

Previous reports suggest cryoglobulinemia might influence the hepatitis C virus (HCV) infection clinical course and treatment response but this association has not been thoroughly evaluated. We aimed to assess the relationship between cryoglobulinemia and sustained viral response (SVR) in patients treated for HCV infection. We included patients with HCV infection treated from January 2003 through December 2006. Biochemical analyses, detection cryoglobulinemia, and liver biopsies were performed prior to treatment. Genotype 1 or 4 infections received Peg-interferon (IFN) alpha-2a or -2b for 48 weeks; genotypes 2 or 3 received IFN alpha for 24 weeks. All patients also received ribavirin. Of 329 enrolled patients, 242 (73%) were male and the median age was 43 years. Cryoglobulinemia was detected in 196 (59.6%) patients; liver biopsy was performed in 301. Multivariate analysis showed an association of cryoglobulinemia with severe active necroinflammation (A3) (adjusted odds ratio [AOR] = 9.48; 95% confidence interval [CI]: 1.50-59.92) and rheumatoid factor (RF) level (AOR = 1.01; 95% CI: 1.00-1.02). Variables associated with advanced fibrosis were age, aspartate aminotransferase and alkaline phosphatase levels, alcohol use, and presence of diabetes. Variables independently associated with SVR were cryoglobulinemia (AOR = 2.33, 95% CI: 1.26-4.32), absence of cirrhosis (AOR = 4.5, 95% CI: 1.4-14.80), and RF level (AOR = 1.008, 95% CI: 1.001-1.014). Our findings suggest cryoglobulinemia is associated with severe necroinflammatory activity in HCV-infected patients. We also provide the first evidence for an association between cryoglobulinemia and higher SVR rates, highlighting its potential role as a prognostic factor for treatment response.