Low revision rate throughout the adoption of the direct superior approach in primary total hip arthroplasty: an analysis based on 1551 total hip arthroplasties from the Dutch Arthroplasty Register.

BACKGROUND: Recently, surgeons introduced a minimally invasive modification on the classic posterolateral approach (PLA) in total hip arthroplasty (THA): the direct superior approach (DSA). We investigated the association between surgeon's experience and the risk of early revision of the DSA in primary THA, using data from the Dutch Arthroplasty Register (LROI). METHODS: We retrieved all primary THAs performed using the DSA in 4 hospitals between 2016 and 2022 (n = 1551). Procedures were sorted in 5 groups using the date of operation and number of previous procedures per surgeon: 1-25; 26-50; 51-75; 76-100; >100. Subsequently, data from different surgeons were pooled together and the risk of revision was calculated via a multilevel time-to-event analysis. RESULTS: The overall revision rate was 1.5% after a mean follow-up of 2 years. Patients from the 1-25 group had comparable risks of revision compared to patients in the >100 group (hazard ratio [HR] 1.0 [CI, 0.3-3.2]). The risk for patients in groups 26-50, 51-75 and 75-100 was also not statistically different from the >100 group (resp. HR 1.5 [CI, 0.5-5.0], 1.8 [CI, 0.5-6.4] and 0.5 [CI, 0.1-4.0]). Main reasons of revision were dislocation (0.5%) and infection (0.4%). CONCLUSIONS: We did not identify an association between the surgeon's experience and the early risk of revision for the DSA in primary THA in the Netherlands. The DSA seems safe in the early adoption phases with a low risk of revision due to dislocation and revision for all other causes.

Omics and imaging combinatorial approach reveals butyrate-induced inflammatory effects in the zebrafish gut.

BACKGROUND: Prebiotic feed additives aim to improve gut health by influencing the microbiota and the gut barrier. Most studies on feed additives concentrate on one or two (monodisciplinary) outcome parameters, such as immunity, growth, microbiota or intestinal architecture. A combinatorial and comprehensive approach to disclose the complex and multifaceted effects of feed additives is needed to understand their underlying mechanisms before making health benefit claims. Here, we used juvenile zebrafish as a model species to study effects of feed additives by integrating gut microbiota composition data and host gut transcriptomics with high-throughput quantitative histological analysis. Zebrafish received either control, sodium butyrate or saponin-supplemented feed. Butyrate-derived components such as butyric acid or sodium butyrate have been widely used in animal feeds due to their immunostimulant properties, thereby supporting intestinal health. Soy saponin is an antinutritional factor from soybean meal that promotes inflammation due to its amphipathic nature. RESULTS: We observed distinct microbial profiles associated with each diet, discovering that butyrate (and saponin to a lesser extent) affected gut microbial composition by reducing the degree of community-structure (co-occurrence network analysis) compared to controls. Analogously, butyrate and saponin supplementation impacted the transcription of numerous canonical pathways compared to control-fed fish. For example, both butyrate and saponin increased the expression of genes associated with immune response and inflammatory response, as well as oxidoreductase activity, compared to controls. Furthermore, butyrate decreased the expression of genes associated with histone modification, mitotic processes and G-coupled receptor activity. High-throughput quantitative histological analysis depicted an increase of eosinophils and rodlet cells in the gut tissue of fish receiving butyrate after one week of feeding and a depletion of mucus-producing cells after 3 weeks of feeding this diet. Combination of all datasets indicated that in juvenile zebrafish, butyrate supplementation increases the immune and the inflammatory response to a greater extent than the established inflammation-inducing anti-nutritional factor saponin. Such comprehensive analysis was supplemented by in vivo imaging of neutrophil and macrophage transgenic reporter zebrafish (mpeg1:mCherry/mpx:eGFPi114) larvae. Upon exposure to butyrate and saponin, these larvae displayed a dose-dependent increase of neutrophils and macrophages in the gut area. CONCLUSION: The omics and imaging combinatorial approach provided an integrated evaluation of the effect of butyrate on fish gut health and unraveled inflammatory-like features not previously reported that question the usage of butyrate supplementation to enhance fish gut health under basal conditions. The zebrafish model, due to its unique advantages, provides researchers with an invaluable tool to investigate effects of feed components on fish gut health throughout life.

INFERYS rescoring: Boosting peptide identifications and scoring confidence of database search results.

Database search engines for bottom-up proteomics largely ignore peptide fragment ion intensities during the automated scoring of tandem mass spectra against protein databases. Recent advances in deep learning allow the accurate prediction of peptide fragment ion intensities. Using these predictions to calculate additional intensity-based scores helps to overcome this drawback. Here, we describe a processing workflow termed INFERYS™ rescoring for the intensity-based rescoring of Sequest HT search engine results in Thermo Scientific™ Proteome Discoverer™ 2.5 software. The workflow is based on the deep learning platform INFERYS capable of predicting fragment ion intensities, which runs on personal computers without the need for graphics processing units. This workflow calculates intensity-based scores comparing peptide spectrum matches from Sequest HT and predicted spectra. Resulting scores are combined with classical search engine scores for input to the false discovery rate estimation tool Percolator. We demonstrate the merits of this approach by analyzing a classical HeLa standard sample and exemplify how this workflow leads to a better separation of target and decoy identifications, in turn resulting in increased peptide spectrum match, peptide and protein identification numbers. On an immunopeptidome dataset, this workflow leads to a 50% increase in identified peptides, emphasizing the advantage of intensity-based scores when analyzing low-intensity spectra or analytes with very similar physicochemical properties that require vast search spaces. Overall, the end-to-end integration of INFERYS rescoring enables simple and easy access to a powerful enhancement to classical database search engines, promising a deeper, more confident and more comprehensive analysis of proteomic data from any organism by unlocking the intensity dimension of tandem mass spectra for identification and more confident scoring.

Comparative and functional analysis of the digital mucus glands and secretions of tree frogs.

BACKGROUND: Mucus and mucus glands are important features of the amphibian cutis. In tree frogs, the mucus glands and their secretions are crucial components of the adhesive digital pads of these animals. Despite a variety of hypothesised functions of these components in tree frog attachment, the functional morphology of the digital mucus glands and the chemistry of the digital mucus are barely known. Here, we use an interdisciplinary comparative approach to analyse these components, and discuss their roles in tree frog attachment. RESULTS: Using synchrotron micro-computer-tomography, we discovered in the arboreal frog Hyla cinerea that the ventral digital mucus glands differ in their morphology from regular anuran mucus glands and form a subdermal gland cluster. We show the presence of this gland cluster also in several other-not exclusively arboreal-anuran families. Using cryo-histochemistry as well as infrared and sum frequency generation spectroscopy on the mucus of two arboreal (H. cinerea and Osteopilus septentrionalis) and of two terrestrial, non-climbing frog species (Pyxicephalus adspersus and Ceratophrys cranwelli), we find neutral and acidic polysaccharides, and indications for proteinaceous and lipid-like mucus components. The mucus chemistry varies only little between dorsal and ventral digital mucus in H. cinerea, ventral digital and abdominal mucus in H. cinerea and O. septentrionalis, and between the ventral abdominal mucus of all four studied species. CONCLUSIONS: The presence of a digital mucus gland cluster in various anuran families, as well as the absence of differences in the mucus chemistry between arboreal and non-arboreal frog species indicate an adaptation towards generic functional requirements as well as to attachment-related requirements. Overall, this study contributes to the understanding of the role of glands and their secretions in tree frog attachment and in bioadhesion in general, as well as the evolution of anurans.

Force-transmitting structures in the digital pads of the tree frog Hyla cinerea: a functional interpretation.

The morphology of the digital pads of tree frogs is adapted towards attachment, allowing these animals to attach to various substrates and to explore their arboreal habitat. Previous descriptions and functional interpretations of the pad morphology mostly focussed on the surface of the ventral epidermis, and little is known about the internal pad morphology and its functional relevance in attachment. In this study, we combine histology and synchrotron micro-computer-tomography to obtain a comprehensive 3-D morphological characterisation of the digital pads (in particular of the internal structures involved in the transmission of attachment forces from the ventral pad surface towards the phalanges) of the tree frog Hyla cinerea. A collagenous septum runs from the distal tip of the distal phalanx to the ventral cutis and compartmentalises the subcutaneous pad volume into a distal lymph space and a proximal space, which contains mucus glands opening via long ducts to the ventral pad surface. A collagen layer connects the ventral basement membrane via interphalangeal ligaments with the middle phalanx. The collagen fibres forming this layer curve around the transverse pad-axis and form laterally separated ridges below the gland space. The topological optimisation of a shear-loaded pad model using finite element analysis (FEA) shows that the curved collagen fibres are oriented along the trajectories of the maximum principal stresses, and the optimisation also results in ridge-formation, suggesting that the collagen layer is adapted towards a high stiffness during shear loading. We also show that the collagen layer is strong, with an estimated tensile strength of 2.0-6.5 N. Together with longitudinally skewed tonofibrils in the superficial epidermis, these features support our hypothesis that the digital pads of tree frogs are primarily adapted towards the generation and transmission of friction rather than adhesion forces. Moreover, we generate (based on a simplified FEA model and predictions from analytical models) the hypothesis that dorsodistal pulling on the collagen septum facilitates proximal peeling of the pad and that the septum is an adaptation towards detachment rather than attachment. Lastly, by using immunohistochemistry, we (re-)discovered bundles of smooth muscle fibres in the digital pads of tree frogs. We hypothesise that these fibres allow the control of (i) contact stresses at the pad-substrate interface and peeling, (ii) mucus secretion, (iii) shock-absorbing properties of the pad, and (iv) the macroscopic contact geometry of the ventral pad surface. Further work is needed to conclude on the role of the muscular structures in tree frog attachment. Overall, our study contributes to the functional understanding of tree frog attachment, hence offering novel perspectives on the ecology, phylogeny and evolution of anurans, as well as the design of tree-frog-inspired adhesives for technological applications.

Gadolinium enhancement in newly diagnosed patients with lumbar disc herniations are associated with inflammatory peridiscal tissue reactions--evidence of fragment degradation?

OBJECTIVE: It is debatable whether a local inflammatory tissue response caused by herniated disc material contributes to sciatic pain and/or sensorimotor deficits. The impact of inflammatory changes on local tissue remodelling, the healing process and the clinical course of disease remains unclear. METHODS: In this prospective observational study, we included a total of 31 patients with a single-level, unilateral lumbar disc herniation. The diagnosis was confirmed by magnetic resonance imaging (MRI)±gadolinium. The presence of peridiscal contrast enhancement was correlated with the extent of inflammatory reactions in the herniated fragments as confirmed by immunohistochemistry; clinical symptoms, including the duration of radicular pain; and the incidence of sensorimotor deficits. RESULTS: Peridiscal contrast enhancement was found in 17 patients (55%) and was encasing the adjacent rootlet in 4 cases. There was no significant correlation between gadolinium uptake and the presence of sensorimotor deficits or the duration of radicular symptoms. Degenerative changes were observed in all 31 disc specimens. Overall, 18 cases exhibited increased cellularity in the marginal areas, which were mostly populated by CD68(+) macrophages and fibroblasts. Additionally, these areas displayed a limited number of CD3(+) T-lymphocytes and different degrees of concomitant neovascularisation, which represented a chronic and unspecific immune response. Peridiscal contrast enhancement on MRI was significantly correlated with the histopathological characteristics of tissue inflammation. However, no correlation was found between the histological evidence and the degree of inflammation and neurological symptoms. CONCLUSION: Gadolinium-enhanced MRI is a sensitive method to detect unspecific inflammatory reactions in therapy-naïve disc herniations. However, the neuroradiological and histological evidence of peridiscal inflammation was not correlated with the severity of pain or sensorimotor deficits in our patients. Additional research is needed because the occurrence of local inflammation may indicate an ongoing degradation of herniated fragments and thus be helpful in therapeutic decision-making.

Vertebral body replacement with PEEK-cages after anterior corpectomy in multilevel cervical spinal stenosis: a clinical and radiological evaluation.

INTRODUCTION: A growing number of industrially manufactured implants have been developed in the last years for vertebral replacement in anterior cervical corpectomy and fusion (ACCF). Polyetheretherketone (PEEK)-cages are used in many centers, but outcome reports are scarce. This study assesses the clinical and radiological outcome after one- or two-level ACCF by the use of a PEEK-cage augmented by a plate-screw osteosynthesis. METHODS: A total of 21 patients received one-level (18 patients) or two-level (3 patients) ACCF by a PEEK-cage and plate-screw osteosynthesis for multilevel degenerative stenosis. The Visual Analogue Scale, Nurick Score, Neck Disability Index and European Myelopathy Score were used for clinical assessment. Radiological outcome-osseous fusion and loss of height-was evaluated by CT. RESULTS: The mean follow-up was 28 ± 12 months. In 19 patients, bony fusion was achieved after the primary operation. Graft failure that required surgical revision occurred in two patients. In these patients, osseous fusion was achieved after the second operation. Myelopathy improved significantly. The loss of height was 2.2 ± 2.3 and 5.3 ± 2.1 mm after one- and two-level ACCF, respectively. CONCLUSION: Anterior corpectomy and fusion by a PEEK-cage and plate-screw osteosynthesis resulted in clinical improvement in all patients. Bony fusion was achieved in all patients in the long run. PEEK cages are allegedly less rigid than other xenografts. Similar to those, however, their use bears the risk of early cage-dislocation and subsidence. A comparison of industrial xenografts and autologous bone implants is required to challenge the different fusion techniques.

Ciprofloxacin-induced hemorrhagic vasculitis.

Ciprofloxacin-induced hemorrhagic vasculitis is a rare side effect. It has only been described in 10 case reports since 1989. However, recently we were confronted with two cases within 1 month. In one patient the vasculitis resolved after termination of the ciprofloxacin therapy; in the other patient the ciprofloxacin-induced hemorrhagic vasculitis was superimposed on a severe forefoot infection, leading to progressive gangrene and a below-knee amputation. Ciprofloxacin is among the standard treatments for infected ischemic ulcers; in the rare case of ciprofloxacin-induced hemorrhagic vasculitis, it might be interpreted as progression of infection, instead of a complication of the treatment, thus leading to faulty diagnosis and treatment. The intention of this case report is to raise awareness for anyone prescribing ciprofloxacin as treatment for infected diabetic and ischemic ulcers.

Hybrid contrast-enhanced MR angiography of pelvic and lower extremity vasculature at 3.0 T: initial experience.

PURPOSE: The objective of this study was to describe contrast-enhanced magnetic resonance angiography (MRA) of the lower extremities at 3.0 T system for assessment of high resolution images in patients with peripheral arterial occlusive disease (PAOD). MATERIAL AND METHODS: 21 Patients with suspected PAOD were examined with four-station MRA at a 3.0 T MR system. The MRA protocol consisted of a hybrid technique with two contrast media injections, the first one for visualization of the calf and foot vasculature (non-moving-table technique), the second one for imaging the aortoiliacal and femoral arteries (moving-table technique). For the femoropopliteal and calf station a randomly segmented central k-space ordering (contrast-enhanced timing-robust angiography [CENTRA]) was used. MR-images were analyzed independently by two radiologists with regard to image quality, venous overlap and grade of stenosis. In 6 patients digital subtraction angiography was performed within the following 7 days and evaluated by two radiologists in consensus with regard to the grade of stenosis. The vasculature-tree of each leg was divided in 12 segments, and 3 anatomical regions (iliacal, femoropopliteal, calf/foot). RESULTS: 490 and 488 of 495 arterial segments were visualized with diagnostic image quality by observer 1 and observer 2, respectively. Image quality was excellent in 470 and 457 arterial segments, respectively. Only 4 segments were rendered as non-diagnostic due to venous overlap. Relevant arterial stenoses (50-99%) were detected in 43 and 47 segments by observer 1 and observer 2, 66 and 65 arterial segments, respectively, were interpreted as occluded. CONCLUSION: The hybrid MRA protocol at 3.0 T offers high diagnostic quality for the whole peripheral arterial tree without venous contamination at high spatial resolution.

Feasibility of peripheral contrast-enhanced magnetic resonance angiography at 3.0 Tesla with a hybrid technique: comparison with digital subtraction angiography.

PURPOSE: To prospectively determine feasibility and diagnostic accuracy of 3D contrast-enhanced MR-angiography (CE-MRA) at 3.0 tesla (T) in patients with peripheral arterial occlusive disease. Digital subtraction angiography (DSA) was used as reference standard. MATERIAL AND METHODS: Thirty consecutive patients with suspected peripheral arterial occlusive disease were examined on a 3.0 T MR system by using the integrated whole body coil. A 4-station examination protocol in hybrid technique was chosen, containing 2 gadodiamide injections, the first one for imaging the calf and foot arteries (single-step technique) and the second injection for the visualization of the aortoiliacal and femoral arteries (bolus-chase MRA). All patients underwent DSA within the following 48 hours. The arterial tree of each leg was divided in 15 segments and 4 anatomic regions (iliacal, femoral, popliteal/proximal calf, distal calf/foot). Two radiologists analyzed the MR-images with regard to image quality, grade of stenosis, and venous overlap. DSA-images were analyzed by 2 radiologists in consensus with regard to the stenosis grade. RESULTS: Eight hundred eighty-five and 884 of 889 arterial segments at CE-MRA were rated with excellent or good diagnostic image quality by observer 1 and observer 2, respectively. In only 3 segments image quality was affected by venous contamination. Sensitivity of CE-MRA for determination of relevant arterial stenoses (50%-99%) and occlusions--as compared with DSA--was 95.3% (both observer) and specificity was 98.5% and 97.8% for observer 1 and observer 2, respectively. CONCLUSION: Peripheral hybrid CE-MRA at 3.0 T is feasible and proved to be reliable at depiction of stenoses and occlusions of the whole pelvic and lower leg arterial system.

Conspicuity of zones of ablation after radiofrequency ablation in porcine livers: comparison of an extracellular and an SPIO contrast agent.

PURPOSE: To compare conspicuity of zones of ablation on nonenhanced, gadopentetate dimeglumine-(Gd-DTPA) and ferucarbotran-(SPIO)-enhanced magnetic resonance (MR) images. MATERIALS AND METHODS: In all, 33 radiofrequency ablations (RFA) were performed in 17 healthy porcine livers at 1.5T MR imaging 1 day and 2 and 4 weeks after RFA: T2-weighted (w) ultra turbo spin echo (UTSE), proton density (PD)-w UTSE, T1-w gradient echo (GRE) pre- and 5 minutes postcontrast administration, dynamic T1-w GRE during Gd-DTPA (Magnevist) or SPIO (Resovist) administration, T2-w UTSE, and PD-w UTSE sequences 10 minutes after SPIO administration. Regions of interest (ROIs) for contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were drawn in consensus by two radiologists. RESULTS: PD-w SPIO-enhanced images (23.5 +/- 5.5) showed higher liver-to-lesion CNR than T1-w GRE Gd-DTPA-enhanced images (13.5 +/- 6.1) 1 day after RFA (P < or = 0.05). At all other timepoints, liver-to-lesion CNR of PD-w and T2-w SPIO-enhanced images did not differ significantly from T1-w GRE Gd-DTPA-enhanced images (P > or = 0.05). Nonenhanced T2-w images revealed lower liver-to-lesion CNR (7.0 +/- 7.5/6.5 +/- 5.9/6.8 +/- 5.0, 1 day/2 weeks/4 weeks, respectively) than T2-w SPIO-enhanced (17.4 +/- 4.8/15.3 +/- 4.5/14.2 +/- 5.7), PD-w SPIO-enhanced (23.5 +/- 5.5/16.9 +/- 3.6, 1 day/2 weeks), and T1-w Gd-DTPA-enhanced (15.3 +/- 3.6/12.7 +/- 3.5, 2/4 weeks) images (P < or = 0.05). Liver-to-lesion CNR of SPIO-enhanced dynamic T1-w GRE images after 30, 80, 150, and 240 seconds did not change significantly over time (P > or = 0.05). CONCLUSION: One day after RFA lesion conspicuity on PD-w ferucarbotran-enhanced images is better than on T1-w GRE Gd-DTPA-enhanced images. At all other timepoints, ferucarbotran is not superior to gadolinium. Ferucarbotran- and gadolinium-enhanced images improve lesion conspicuity compared with nonenhanced T2-w images at all timepoints.

MR imaging of claustrophobic patients in an open 1.0T scanner: motion artifacts and patient acceptability compared with closed bore magnets.

OBJECTIVE: To evaluate motion artifacts and patient acceptability of MR imaging of claustrophobic patients in an open 1.0T scanner. SUBJECTS AND METHODS: Thirty six claustrophobic patients were enrolled prospectively, 34 of which had previous MR examinations in closed bore magnets. Anxiety and pain during MR examination in an open 1.0T scanner were evaluated by visual analogue scales and various tests. Influence of motion artifacts on image quality was evaluated by two radiologists independently using a five-point scale. Additionally, 36 non-claustrophobic patients delivered a reference value of a non-claustrophobic population for the visual analogue anxiety scale. RESULTS: Termination rate of MR imaging of highly claustrophobic patients decreased from 58.3% (n=21) in closed bore magnets to 8.3% (n=3) in the open scanner (p

The smoothness of shaven beards: the relation between stubble length distribution and skin parameters and tactile smoothness.

In this report we describe how the tactile smoothness of shaven beards depends on the distribution of the stubble lengths remaining after shaving and on various skin parameters like coarseness and scaliness. To this end, we set up two experiments on perceived smoothness with blinded human judges. In the first experiment we used artificial beards with various stubble length distributions and stubble densities as stimuli. In the second experiment we presented freshly shaven human beards, for which a wide range of objective skin and stubble parameters had been measured, as stimuli. The results of the two experiments are mostly in line with each other. We can conclude that there are individual differences between judges in the aspects they pay attention to when judging tactile smoothness. Nevertheless, a general line is discernable, and we can identify three parameters that influence the impression of tactile smoothness: the orientation of the stubble, the density of the stubble, and the length of the hairs in the stubble length distribution. We have also established the relative importance of the latter two effects.

The Strengths and Difficulties Questionnaire (SDQ)--further evidence for its reliability and validity in a community sample of Dutch children and adolescents.

This study was a first attempt to examine the psychometric properties of the Strengths and Difficulties Questionnaire (SDQ) in Dutch youths. A large sample of normal children and adolescents ( N = 562) and their parents completed the SDQ along with a number of other psychopathology measures. Factor analysis of the SDQ yielded five factors that were in keeping with the hypothesised subscales of hyperactivity-inattention, emotional symptoms, peer problems, conduct problems, and prosocial behaviour. Furthermore, internal consistency, test-retest stability, and parent-youth agreement of the various SDQ scales were acceptable. Finally, the concurrent validity of the SDQ was good: that is, its scores correlated in a theoretically meaningful way with other measures of psychopathology. It can be concluded that the psychometric properties of the parent- and self-report version of the SDQ were satisfactory in this Dutch community sample. Moreover, the current data provide further support for the utility of the SDQ as an index of psychopathological symptoms in youths.

Ca2+-activated, large conductance K+ channel in the ovary: identification, characterization, and functional involvement in steroidogenesis.

Progesterone production by the corpus luteum is a process vital for reproduction. In humans its secretion is stimulated by the placental hormone human chorionic gonadotropin (hCG), and this stimulatory action can also be observed in cultured human luteinized granulosa cells (GCs). We now provide evidence that opening of a Ca(2+)-activated K(+) channel, the BK(Ca), is crucially involved in this process. Immunohistochemistry and RT-PCR revealed the presence of the pore-forming alpha-subunit in human luteinized GCs and in luteal cells of human, macaque, and rat, implying that BK(Ca) channels are important throughout species. Blocking of BK(Ca) channels by iberiotoxin attenuated hCG-induced progesterone secretion. The inhibitory action of iberiotoxin suggests that BK(Ca) channels are activated in the course of hCG-induced steroidogenesis. In search of physiological activators we used an electrophysiological approach and could preclude a direct regulation of channel activity by hCG or GC-derived steroids (progesterone and 17beta-estradiol). Instead, the peptide hormone oxytocin and an acetylcholine (ACh) agonist, carbachol, evoked transient BK(Ca) currents and membrane hyperpolarization. These two molecules are both secreted by GCs and act via raised intracellular Ca(2+) levels. The release of oxytocin is stimulated by hCG, and a similar mechanism is likely in the case of ACh. We conclude that BK(Ca) channel activity in GCs is mediated by components of the intraovarian signaling system, thereby interlinking a systemic hormonal and a local neuroendocrine system in control of steroidogenesis.

CD44 expression in IgA nephropathy.

Immunoglobulin A (IgA) nephropathy is a frequent, chronic renal disease characterized by a broad spectrum of clinical presentations and pathologic findings. CD44, a family of type I transmembrane glycoproteins involved in cell-cell and cell-matrix interactions, may orchestrate partially the cascade of inflammation, accumulation of myofibroblasts, and fibrosis leading to end-stage renal disease. To clarify the possible role of CD44 in the progression of IgA nephropathy, the expression of CD44 in glomeruli and the tubulointerstitial compartment was analyzed in 25 renal biopsy specimens of patients with IgA nephropathy and was correlated to histopathologic, serologic, and urinary parameters. The expression of CD44 correlated significantly with the degree of glomerular and interstitial damage, even better than the accumulation of alpha-smooth muscle actin-positive myofibroblasts, which is recognized as a reliable marker for the progression of IgA nephropathy. A positive correlation also was found between proteinuria and the expression of CD44 in the tubulointerstitial compartment. The glomerular and tubulointerstitial expression of CD44 correlated with the degree of renal damage in IgA nephropathy and could be a reliable marker of the progression of IgA nephropathy. CD44 may have a pivotal role in the cascade of renal inflammation and fibrosis.