Search

Background: Renal volume (RV) is associated with renal function and with a variety of cardiovascular risk factors (CVRFs). We analysed RV using magnetic resonance imaging (MRI) in a large population-based study (Study of Health in Pomerania; SHIP-TREND) to find sex- and age-specific reference values for RV and to test the influence of several markers on RV. The main objective is to describe reference values for RV in people from the general population without kidney disease., Methods: 1815 participants without kidney disease (930 women) aged 21-81 years were included in our study. Right and left RV with and without body surface area (BSA) indexation were compared among three age groups (22-39 years, 40-59 years, 60-81 years) by median and interquartile range and tested separately in women and men., Results: The estimated glomerular filtration rate (eGFR), serum uric acid, and right and left RV were higher in men compared to women (all p < 0.001). Left kidneys were larger than right kidneys (both sexes). With age, RV showed a continuously decreasing trend in women and an upside-down U-shaped relation in men. In multivariable linear regression models, current smoking (β = 14.96, 95% CI 12.12; 17.79), BSA (β = 97.66, 95% CI 90.4; 104.93), diastolic blood pressure (β = 0.17, 95% CI 0.01; 0.32), and eGFR (β = 0.57, 95% CI 0.50; 0.65) were positively associated with both left and right RV, whereas uric acid (β = -0.03, 95% CI -0.05; -0.01) showed an inverse association with RV. Interestingly, the same eGFR correlated with higher RV in men compared to women., Conclusion: Reference values for RV are different for age groups and sex. For any given age, female kidneys are smaller than male kidneys. RV associates positively with eGFR, but for any chosen eGFR, renal volume in females is lower compared to males. RV decreases with age, but in men showed a U-shaped correlation. This may reflect hyperfiltration and glomerular hypertrophy associated with the presence of CVRF in middle-aged males.

In recent years, there has been a surge of interest in tumor microenvironment-associated cancer vaccine therapies. These innovative treatments aim to activate and enhance the body's natural immune response against cancer cells by utilizing specific antigens present in the tumor microenvironment. The goal is to achieve a complete clinical response, where all measurable cancer cells are either eliminated or greatly reduced in size. With their potential to revolutionize cancer treatment, these therapies represent a promising avenue for researchers and clinicians alike. Despite over 100 years of research, the success of therapeutic cancer vaccines has been variable, particularly in advanced cancer patients, with various limitations, including the heterogeneity of the tumor microenvironment, the presence of immunosuppressive cells, and the potential for tumor escape mechanisms. Additionally, the effectiveness of these therapies may be limited by the variability of the patient's immune system response and the difficulty in identifying appropriate antigens for each patient. Despite these challenges, tumor microenvironment-targeted vaccine cancer therapies have shown promising results in preclinical and clinical studies and have the potential to become a valuable addition to current cancer treatment and "curative" options. While chemotherapeutic and monoclonal antibody treatments remain popular, ongoing research is needed to optimize the design and delivery of these therapies and to identify biomarkers that can predict response and guide patient selection. This comprehensive review explores the mechanisms of cancer vaccines, various delivery methods, and the role of adjuvants in improving treatment outcomes. It also discusses the historical background of cancer vaccine research and examines the current state of major cancer vaccination immunotherapies. Furthermore, the limitations and effectiveness of each vaccine type are analyzed, providing insights into the future of cancer vaccine development.

Large-scale target cell isolation from patient blood preparations is one of the critical operations during drug product manufacturing for personalized cell therapy in immuno-oncology. Use of high-affinity murine antibody coated magnetic nanoparticles that remain on isolated cells is the current standard applied for this purpose. Here, we present the transformation of previously described technology - non-magnetic immunoaffinity column chromatography-based cell selection with reversible reagents into a new clinical-grade cell isolation platform called Automated Traceless Cell affinity chromatography (ATC). ATC is a fully closed and GMP-compliant cell selection and manufacturing system. Reversibility of reagents enables (sequential) positive cell selection, optionally in combination with depletion columns, enabling capture of highly specific cell subsets. Moreover, synergy with other Streptamer-based technologies allows novel uses beyond cell isolation including integrated and automated on-column target cell activation. In conclusion, ATC technology is an innovative as well as versatile platform to select, stimulate and modify cells for clinical manufacturing and downstream therapies., (© 2022. The Author(s).)

Objective: To statistically analyze the long-term results of osteotomy after rhinoplasty., Design: In a consecutive series of 51 patients who underwent reduction rhinoplasty from May 1, 2000, through September 30, 2003, all underwent the same method of bilateral lateral osteotomies, performed by one of us. Twenty patients agreed to participate in this study. The follow-up ranged from 7 to 36 months (mean, 12.6 months). By using preoperative and postoperative photographs, comparisons were made of the change in the dorsal width of the nose (the anterior junction of the nasal bones) and of the ventral width of the nose (where the nasal processes of the maxilla meet the body of the maxilla)., Results: There was a significant change (P = .003) in the ventral width of the nose after nasal bone osteotomy. There was no significant change (P = .24) in the dorsal width of the nose., Conclusions: By using this technique of osteotomy, it is possible to narrow the ventral width of the nose with statistical significance. The dorsal width of the nose is maintained in reduction rhinoplasty. To our knowledge, this is the first attempt to quantify the amount of narrowing achieved after nasal osteotomies.

Objective: To ascertain the reliability of a proposed method for quantifying tissue eosinophilia in sinus mucosa., Design: Prospective cohort study., Interventions and Outcome Measures: Pathology slides from patients undergoing endoscopic sinus surgery for chronic rhinosinusitis were independently assessed by 2 reviewers. Using a proposed systematic counting method, the degree of tissue eosinophilia was quantified. Disease severity was assessed by computed tomographic (CT) staging. Intrarater, interrater, and intrapatient reliability was determined using correlational reliability analysis. The degree of correlation between tissue eosinophilia and CT stage was determined., Results: One hundred thirty-two slides from 65 patients were reviewed. The mean (SD) eosinophil density was 23.4 (37.2) eosinophils per high-power field. Only 12 patients (18%) had no eosinophils on histopathologic analysis. Strong intrarater (r> or =0.91 for each rater, P<.001) and interrater reliability (r> or =0.82 between raters, P<.001) was noted for the quantification method. A moderate degree of correlation was found between CT scan stage and degree of tissue eosinophilia (Spearman rho = 0.62, P<.001)., Conclusions: The proposed method for quantifying tissue eosinophilia in sinus mucosa is reliable and valid. A relatively strong correlation exists between CT scan stage and tissue eosinophilia in chronic rhinosinusitis.

The outer supporting cells in the apical turns of the guinea pig cochlea receive a dense innervation. Our previous study (Fechner et al. [1998] J. Comp. Neurol. 400:299-300) suggested that this innervation of the Deiters' and Hensen's supporting cells was not derived from efferent fibers of the olivocochlear bundle, but its origin has not been further specified. To test the hypothesis that the innervation was afferent in origin, we traced apical afferent fibers that were retrogradely labeled by extracellular injections of horseradish peroxidase. Labeled afferent fibers were of two types: type I fibers contacted inner hair cells, whereas type II fibers crossed the tunnel and contacted outer hair cells. Significantly, most of the type II fibers also formed branches to the outer supporting cells. Although a few olivocochlear efferent fibers formed such branches, counts indicated that the overwhelming majority of the branches were produced by type II afferent fibers. These branches were not produced by basal type II fibers. Apical type II fibers also differed from basal fibers by having shorter lengths, spiraling both apically and basally, and contacting all three rows of outer hair cells. These innervation differences suggest differences in the ways that information from outer hair cells is processed in the apex versus the base of the cochlea., (Copyright 2000 Wiley-Liss, Inc.)

Innervation of Deiters' and Hensen's cells has been described in the organ of Corti of several mammalian species and has been suggested to arise from the olivocochlear (OC) efferent system (Wright and Preston [1976] Acta Otolaryngol. 82:41-47). In the present study, antineurofilament immunostaining was used to reveal these outer supporting cell fibers (OSCFs) in the normal guinea pig. In control ears, OSCFs were absent in the basal half of the cochlea but increased in number steadily toward the apex, peaking at values of over 1,200 fibers/mm. These values indicate a far more profuse innervation of supporting cells than has been described previously, suggesting that most OSCFs were not stained in previous immunohistochemical studies. Chronic cochlear deefferentation was used to test whether OSCFs are part of the OC system. The OC bundle was transected unilaterally, and the animals were allowed to survive for 4-8 weeks. Completeness of deefferentation was assessed by using acetylcholinesterase staining of the brainstem and measurement of the density of OC fascicles in the cochlea. By using these metrics, unilateral deefferentation was nearly complete in three animals. In successfully deefferented cases, the OSCF innervation density was not statistically different from control values. We conclude that the vast majority of OSCFs are not of OC origin. We speculate that they may be branches of type II afferent fibers to outer hair cells and that a smaller population of OSCFs with different morphology and immunoreactivity may arise from the OC system.

Interleukin-6 (IL-6) is supposed to be a growth factor in multiple myeloma (MM). Applying a bioassay and a modified ELISA, we measured serum IL-6 values in 64 patients with overt MM, seven patients with smouldering myeloma (SMM), 57 patients with monoclonal gammopathy of undetermined significance (MGUS) and 40 healthy volunteers as controls. IL-6 failed to discriminate between MGUS and MM, stage I, whereas comparison of MM, stage I and stage II/III (p = 0.0143), or comparison of stable disease/remission and progressive disease (p < 0.0001) revealed significant differences. Furthermore, we found significantly higher IL-6 values in overt MM compared to SMM (p = 0.0018). Using a Ki67/CD38 immunohistological double staining method we found a significant correlation between proliferation of bone marrow myeloma cells and serum IL-6 values in 15 patients (p = 0.005). These data demonstrate that IL-6 is a parameter of disease activity in MM and, beside its role in tumor biology, may become a valuable supplement to the established risk factors when selecting patients with unfavourable clinical course for more aggressive treatment modalities.