48 h Normothermic Machine Perfusion With Urine Recirculation for Discarded Human Kidney Grafts.

Normothermic machine perfusion (NMP) has reshaped organ preservation in recent years. In this preclinical study, prolonged normothermic perfusions of discarded human kidney grafts were performed in order to investigate perfusion dynamics and identify potential quality and assessment indicators. Five human discarded kidney grafts were perfused normothermically (37°C) for 48 h using the Kidney Assist device with a red-blood-cell based perfusate with urine recirculation. Perfusion dynamics, perfusate and urine composition as well as injury markers were measured and analyzed. Donor age ranged from 41 to 68 years. All but one kidney were from brain dead donors. Perfusions were performed successfully for 48 h with all discarded kidneys. Median arterial flow ranged from 405 to 841 mL/min. All kidneys excreted urine until the end of perfusion (median 0.43 mL/min at the end of perfusion). While sodium levels were consistently lower in urine compared to perfusate samples, this was only seen for chloride and potassium in kidney KTX 2. Lactate, AST, LDH as well as pro-inflammatory cytokines increased over time, especially in kidneys KTX 3 and 4. Ex vivo normothermic perfusion is able to identify patterns of perfusion, biological function, and changes in inflammatory markers in heterogenous discarded kidney grafts.

Forty-eight hours of normothermic kidney preservation applying urine recirculation.

Kidney transplantation is limited due to the organ scarcity and the large discrepancy between transplantable organs and patients on the waiting list. Ex-situ normothermic kidney preservation has been studied extensively as a tool to enlarge the donor pool and to enable viability assessment. Urine recirculation, for volume control, was applied to perfuse a discarded human kidney for 48 hours. Long-term kidney NMP was feasible under stable hemodynamic conditions with a physiological acid-base-balance and an intact histological morphology of the organ.

SARS-CoV-2 infection and recurrence of anti-glomerular basement disease: a case report.

BACKGROUND: Anti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection. CASE PRESENTATION: The 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome. CONCLUSION: Our case supports the assumption of a possible association between COVID-19 and anti-GBM disease.

Successful pregnancy in a patient with pulmonary renal syndrome double-positive for anti-GBM antibodies and p-ANCA
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BACKGROUND: Antiglomerular basement membrane (anti-GBM) antibody disease is a rare condition causing pulmonary hemorrhage and necrotizing glomerulonephritis (pulmonary renal syndrome). CASE: We report a 30-year-old woman who presented with life-threatening pulmonary hemorrhage and an active urinary sediment, with normal glomerular filtration rate in the 13th week of pregnancy. Anti-GBM antibodies in serum were negative, but perinuclear antineutrophil cytoplasmatic antibodies (p-ANCA) were detected. A renal biopsy revealed necrotizing glomerulonephritis with linear IgG deposits along the glomerular basement membrane. A diagnosis of pulmonary renal syndrome caused by anti-GBM antibodies and p-ANCA (double-positive) was made. Plasma exchange was started but had to be changed to immunoadsorption because of an allergic reaction to fresh frozen plasma. Oral steroids were introduced. The patient also received one dose of intravenous cyclophosphamide followed by two 1-g doses of rituximab. The patient responded quickly to treatment with resolution of pulmonary hemorrhage and urinary abnormalities. The infant was delivered in the 38th week of pregnancy by caesarian section. It was small for age but otherwise completely healthy with a normal B-cell count. CONCLUSION: To our knowledge, this is the first report of a double-positive pulmonary renal syndrome in pregnancy. Presentation in mid-pregnancy allowed for the application of cyclophosphamide without causing malformations and rituximab without B-cell depletion in the infant.
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Successful management of recurrent focal segmental glomerulosclerosis.

Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5-year-old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure that was resistant to plasmapheresis and rituximab. After exclusion of structural or immunologic damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52-year-old second recipient who had vascular nephropathy. Immediately after retransplantation, the allograft regained function with excellent graft function persistent now at 3 years after transplant. After 2 years on hemodialysis, the boy was listed for kidney retransplantation. To prevent FSGS recurrence, pretreatment with ofatumumab was performed. Nephrotic range proteinuria still occurred after the second transplantation, which responded, however, to daily plasma exchange in combination with ofatumumab. At 8 months after kidney retransplantation graft function is good. The clinical course supports the hypothesis of a circulating permeability factor in the pathogenesis of FSGS. Successful ofatumumab pretreatment implicates a key role of B cells. Herein we provide a description of successful management of kidney failure by FSGS, carefully avoiding waste of organs.

Increased accuracy of a novel mRNA-based urine test for bladder cancer surveillance.

OBJECTIVES: To evaluate the diagnostic accuracy of the Xpert Bladder Cancer (BC) Monitor, compared with cystoscopy and cytology in the oncological follow-up of non-muscle-invasive bladder cancer (NMIBC). MATERIAL AND METHODS: A total of 140 patients with a history of NMIBC undergoing routine surveillance at our institution were enrolled prospectively in this study (ISRCTN study registry number 37210907). Urine cytology was evaluated according to the Paris classification system. In addition, urinary specimens were analysed using the Xpert BC Monitor, which measures five target mRNAs (ABL1, CRH, IGF2, UPK1B, ANXA10) using real-time PCR. Descriptive analysis, diagnostic accuracy including sensitivity, specificity, positive (PPV) and negative predictive value (NPV), receiver-operating characteristic curve, and area under the curve (AUC) were calculated. RESULTS: The overall sensitivity (0.84) and NPV (0.93) of the Xpert BC Monitor were significantly superior to those of bladder washing cytology (0.33 and 0.76; P < 0.001). Subgroup analyses confirmed the high sensitivity of the Xpert BC Monitor even in low-grade (0.77) and pTa (0.82) disease compared with barbotage cytology (low-grade: 0.13; pTa: 0.21). The overall specificity of the Xpert BC Monitor and barbotage cytology was similar (0.91 vs 0.94; P = 0.41). Combining the Xpert BC Monitor with barbotage cytology (AUC = 0.85) did not enhance diagnostic performance compared with the performance of the Xpert BC Monitor alone (AUC = 0.87). CONCLUSION: In this study, we report for the first time that the Xpert BC Monitor, a new mRNA-based urine test, outperforms cytology with regard to sensitivity and NPV, even in low-grade and pTa tumours, with no reduction of specificity.

Intraductal tubulopapillary neoplasm (ITPN) of the pancreas associated with an invasive component: a case report with review of the literature.

BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) depicts a distinct entity in the subgroup of premalignant epithelial tumors of the pancreas. Although the histomorphological and immunophenotypical characterization of ITPN has been described by several authors in terms of report of case series in the past, the rarity of that tumor subtype and similarity to other entities still makes identification of ITPN a challenge for radiologists and pathologists. To date, little is known about tubulopapillary carcinoma that can evolve from ITPN. CASE PRESENTATION: In the present work, we analyze one case of ITPN associated with an invasive component and discuss the results involving the current literature. Collected patient data included medical history, clinical symptoms, laboratory tests, radiological imaging, reports of interventions and operation, and histopathological and immunohistochemical examinations. The patient initially presented with acute pancreatitis. A solid tumor obstructing the main pancreatic duct and sticking out of the papilla of Vater was detected and caught via endoscopic intervention. Histopathological examination of the specimen revealed mainly tubular growth pattern with back to back tubular glands. Immunohistochemically, the tumor was strongly positive for keratin 7 (CK7) and pankeratin AE1/AE3, and alpha 1 antichymotrypsin; negative for synaptophysin and chromogranin A, CDx2, CK20, S100, carcinoembryonic antigen (CEA), MUC 2, MUC5AC, and somatostatin; and in part positive for CA19-9. Extended pancreatoduodenectomy was performed, the final diagnosis was tubulopapillary carcinoma grown in an ITPN. CONCLUSION: The identification of an ITPN of the pancreas can be a challenging task. Endoscopic retrograde cholangiopancreaticography is an excellent tool to directly see and indirectly visualize the intraductal solid tumor and to take a biopsy for histopathological evaluation at the same time. Together with a thorough immunohistochemical workup, differential diagnoses can be ruled out quickly. To date, reports of ITPN are rare and little is known about the potential for malignant transformation and the prognosis of tubulopapillary carcinoma grown from an ITPN. Radical surgical resection following oncologic criteria is recommended; however, more data will be needed to assess an adequate treatment and follow-up standard.

Interleukin-6 receptor alpha blockade improves skin lesions in a murine model of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by antinuclear autoantibodies (ANA) and immunocomplexes, commonly affecting kidneys, skin, heart, lung or even the brain. We have shown that JunB(Δep) mice develop a SLE phenotype linked to increased epidermal Interleukin (IL)-6 secretion. Blocking of IL-6 receptor alpha (IL-6Rα) is considered as therapeutic strategy for the treatment of SLE. JunB(Δep) and wild-type mice were treated for short (5 weeks) or long term (21 weeks) with the IL-6Rα-blocking antibody MR16-1. Skin and kidney of mice were investigated by histology and immunofluorescence, and in addition, kidneys were analysed by electron microscopy. Furthermore, soluble IL-6R (sIL-6R), antihistone and antinucleosome antibodies levels were measured and associated with disease parameters. Treatment with MR16-1 resulted in significant improvement of SLE-like skin lesions in JunB(Δep) mice, compared to untreated mice. The sIL-6R amount upon long-term treatment with MR16-1 was significantly higher in JunB(Δep) versus untreated JunB(Δep) (P = 0.034) or wild-type mice (P = 0.034). MR16-1 treatment over these time spans did not significantly improve kidney pathology of immunoglobulin deposits causing impaired function. Significantly higher antihistone (P = 0.028) and antinucleosome antibody levels (P = 0.028) were measured in MR16-1-treated JunB(Δep) mice after treatment compared to levels before therapy. In conclusion, blockade of IL-6Rα improves skin lesions in a murine SLE model, but does not have a beneficial effect on autoimmune-mediated kidney pathology. Inhibition of IL-6R signalling might be helpful in lupus cases with predominant skin involvement, but combinatorial treatment might be required to restrain autoantibodies.

Use of Calcium Channel Blockers is Associated with Mortality in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS: The use of antihypertensive medicines has been shown to reduce proteinuria, morbidity, and mortality in patients with chronic kidney disease (CKD). A specific recommendation for a class of antihypertensive drugs is not available in this population, despite the pharmacodynamic differences. We have therefore analysed the association between antihypertensive medicines and survival of patients with chronic kidney disease. METHODS: Out of 2687 consecutive patients undergoing kidney biopsy a cohort of 606 subjects with retrievable medical therapy was included into the analysis. Kidney function was assessed by glomerular filtration rate (GFR) estimation at the time point of kidney biopsy. Main outcome variable was death. RESULTS: Overall 114 (18.7%) patients died. In univariate regression analysis the use of alpha-blockers and calcium channel antagonists, progression of disease, diabetes mellitus (DM) type 1 and 2, arterial hypertension, coronary heart disease, peripheral vascular disease, male sex and age were associated with mortality (all p<0.05). In a multivariate Cox regression model the use of calcium channel blockers (HR 1.89), age (HR 1.04), DM type 1 (HR 8.43) and DM type 2 (HR 2.17) and chronic obstructive pulmonary disease (HR 1.66) were associated with mortality (all p < 0.05). CONCLUSION: The use of calcium channel blockers but not of other antihypertensive medicines is associated with mortality in primarily GN patients with CKD.

Outcome of chemotherapy extravasation in a large patient series using a standardised management protocol.

PURPOSE: In a longitudinal observation, extravasation of antitumoural compounds and the efficacy of its structured interdisciplinary management were assessed in a routine setting. METHODS: One hundred sixty-nine patients with extravasation of cytotoxics were managed according to a prospective approach documenting the extravasated compound, localisation, duration until full symptom resolution and sequelae. Surgery was implemented in the case of failure of conservative measures. RESULTS: In 155 (91.7 %) out of 169 patients, conservative management was successful (surgical intervention, 14 patients). Extravasations of anthracyclines (N = 44), platinum compounds (N = 41), vinca alkaloids (N = 20) and taxanes (N = 19) were often associated with erythema, oedema and pain. The median period until full resolution of symptoms differed among the administered cytotoxics (anthracyclines, 55 days; taxanes and vinca alkaloids, 27 days; platinum compounds, 14 days) with statistical significance between the vesicants. Histologically, surgically resected specimens showed extensive necrotic areas with inflammatory infiltrates at the periphery of the removed lesions. CONCLUSIONS: In a routine setting, the standardised management of cytotoxic extravasations by an interdisciplinary task force resulted in a satisfactory outcome. When surgical intervention was indicated, complete remission of the lesions within a median of 14 days reduced the delay in the administration of further chemotherapy to a minimum. The proposed approach is therefore considered as suitable to manage extravasations in cancer chemotherapy in a large number of subjects and to ensure patient adherence to cytotoxic treatment.

Interphalangeal Osteoarthritis Radiographic Simplified (iOARS) score: a radiographic method to detect osteoarthritis of the interphalangeal finger joints based on its histopathological alterations.

OBJECTIVE: To develop a radiographic score for assessment of hand osteoarthritis (OA) that is based on histopathological alterations of the distal (DIP) and proximal (PIP) interphalangeal joints. METHODS: DIP and PIP joints were obtained from corpses (n=40). Plain radiographies of these joints were taken. Joint samples were prepared for histological analysis; cartilage damage was graded according to the Mankin scoring system. A 2×2 Fisher's exact test was applied to define those radiographic features most likely to be associated with histological alterations. Receiver operating characteristic curves were analysed to determine radiographic thresholds. Intraclass correlation coefficients (ICC) estimated intra- and inter-reader variability. Spearman's correlation was applied to examine the relationship between our score and histopathological changes. Differences between groups were determined by a Student's t test. RESULTS: The Interphalangeal Osteoarthritis Radiographic Simplified (iOARS) score is presented. The score is based on histopathological changes of DIP and PIP joints and follows a simple dichotomy whether OA is present or not. The iOARS score relies on three equally ranked radiographic features (osteophytes, joint space narrowing and subchondral sclerosis). For both DIP and PIP joints, the presence of one x-ray features reflects interphalangeal OA. Sensitivity and specificity for DIP joints were 92.3% and 90.9%, respectively, and 75% and 100% for PIP joints. All readers were able to reproduce their own readings in DIP and PIP joints after 4 weeks. The overall agreement between the three readers was good; ICCs ranged from 0.945 to 0.586. Additionally, outcomes of the iOARS score in a hand OA cohort revealed a higher prevalence of interphalangeal joint OA compared with the Kellgren and Lawrence score. CONCLUSIONS: The iOARS score is uniquely based on histopathological alterations of the interphalangeal joints in order to reliably determine OA of the DIP and PIP joints radiographically. Its high specificity and sensitivity together with the dichotomous approach renders the iOARS score reliable, fast to perform and easy to apply. This tool may not only be valuable in daily clinical practice but also in clinical and epidemiological trials.

Kidney biopsy results versus clinical parameters on mortality and ESRD progression in 2687 patients with glomerulonephritis.

BACKGROUND: Physicians refer proteinuric patients to kidney biopsy in order to clarify the issue of underlying renal disease. We compared kidney biopsy results with classical outcome parameters in a large cohort of patients with biopsy proven glomerulonephritis (GN). METHODS: In a retrospective analysis, 2687 patients with different forms of GN from 123 Austrian centres were investigated. Patient characteristics, the diagnosis of GN and its respective subtype and clinical symptoms such as arterial hypertension, haematuria, amount of proteinuria and estimated glomerular filtration rate (eGFR) were tested for their association with all-cause mortality and progression to end-stage renal disease (ESRD). RESULTS: During a median follow-up of 129·9 months (IQR 89·6; 177·7), 688 patients (25·6%) died and 718 patients required dialysis (29·4%). In multivariate Cox's regression analysis age (HR 1·06), female sex (HR 0·71), eGFR (HR 0·74), the diagnosis of GN and its subtypes predicted patient survival (all P < 0·01), whereas the amount of proteinuria was not associated with patient survival. The incidence of progression to ESRD was associated with female sex (HR 0·71), eGFR (HR 0·65), amount of proteinuria (HR 1·15) and the diagnosis of GN and its subtypes (all P < 0·01). Nephrotic or nephritic syndromes were not associated with patient survival or progression to ESRD and did not add further predictive value to outcome of GN. CONCLUSIONS: Our study demonstrates histological diagnosis of GN and its specific subtype predicts patient survival and dialysis incidence. Therefore, kidney biopsy should be an integral part of routine diagnostic assessment in patients with any forms of suspected GN.

A p38MAPK/MK2 signaling pathway leading to redox stress, cell death and ischemia/reperfusion injury.

BACKGROUND: Many diseases and pathological conditions are characterized by transient or constitutive overproduction of reactive oxygen species (ROS). ROS are causal for ischemia/reperfusion (IR)-associated tissue injury (IRI), a major contributor to organ dysfunction or failure. Preventing IRI with antioxidants failed in the clinic, most likely due to the difficulty to timely and efficiently target them to the site of ROS production and action. IR is also characterized by changes in the activity of intracellular signaling molecules including the stress kinase p38MAPK. While ROS can cause the activation of p38MAPK, we recently obtained in vitro evidence that p38MAPK activation is responsible for elevated mitochondrial ROS levels, thus suggesting a role for p38MAPK upstream of ROS and their damaging effects. RESULTS: Here we identified p38MAPKα as the predominantly expressed isoform in HL-1 cardiomyocytes and siRNA-mediated knockdown demonstrated the pro-oxidant role of p38MAPKα signaling. Moreover, the knockout of the p38MAPK effector MAPKAP kinase 2 (MK2) reproduced the effect of inhibiting or knocking down p38MAPK. To translate these findings into a setting closer to the clinic a stringent kidney clamping model was used. p38MAPK activity increased upon reperfusion and p38MAPK inhibition by the inhibitor BIRB796 almost completely prevented severe functional impairment caused by IR. Histological and molecular analyses showed that protection resulted from decreased redox stress and apoptotic cell death. CONCLUSIONS: These data highlight a novel and important mechanism for p38MAPK to cause IRI and suggest it as a potential therapeutic target for prevention of tissue injury.

Rationale and design of the Innsbruck Diabetic Kidney Disease Cohort (IDKDC)-a prospective study investigating etiology and progression of early-stage chronic kidney disease in type 2 diabetes.

Background: The development of chronic kidney disease (CKD) in about 20%-40% of patients with type 2 diabetes (T2D) aggravates cardiovascular morbidity and mortality. Pathophysiology is of increasing relevance for individual management and prognosis, though it is largely unknown among T2D patients with CKD as histologic work-up is not routinely performed upon typical clinical presentation. However, as clinical parameters do not appropriately reflect underlying kidney pathology, reluctance regarding timely histologic assessment in T2D patients with CKD should be critically questioned. As the etiology of CKD in T2D is heterogeneous, we aim to assess the prevalence and clinical disease course of typical diabetic vs atypical/non-specific vs non-diabetic vs coexisting kidney pathologies among T2D patients with mild-to-moderate kidney impairment [KDIGO stage G3a/A1-3 or G2/A2-3; i.e. estimated glomerular filtration rate (eGFR) 59-45 mL/min irrespective of albuminuria or eGFR 89-60 mL/min and albuminuria >30 mg/g creatinine]. Methods: The Innsbruck Diabetic Kidney Disease Cohort (IDKDC) study aims to enroll at least 65 T2D patients with mild-to-moderate kidney impairment to undergo a diagnostic kidney biopsy. Six-monthly clinical follow-ups for up to 5 years will provide clinical and laboratory data to assess cardio-renal outcomes. Blood, urine and kidney tissue specimen will be biobanked to identify diagnostic and prognostic biomarkers. Conclusions: While current risk assessment is primarily based on clinical parameters, our study will provide the scientific background for a potential change of the diagnostic standard towards routine kidney biopsy and clarify its role for individual risk prediction regarding cardio-renal outcome in T2D patients with mild-to-moderate kidney impairment.

Shear-Wave Elastography Gradient Analysis of Newly Diagnosed Breast Tumours: A Critical Analysis.

BACKGROUND: A better understanding of the peritumoral stroma changes due to tumour invasion using non-invasive diagnostic methods may improve the differentiation between benign and malignant breast lesions. This study aimed to assess the correlation between breast lesion differentiation and intra- and peritumoral shear-wave elastography (SWE) gradients. METHODS: A total of 135 patients with newly diagnosed breast lesions were included. Intratumoral, subsurface, and three consecutive peritumoral SWE value measurements (with three repetitions) were performed. Intratumoral, interface, and peritumoral gradients (Gradient 1 and Gradient 2) were calculated using averaged SWE values. Statistical analysis included descriptive statistics and an ordinary one-way ANOVA to compare overall and individual gradients among Breast Imaging-Reporting and Data System (BI-RADS) 2, 3, and 5 groups. RESULTS: Malignant tumours showed higher average SWE velocity values at the tumour centre (BI-RADS 2/3: 4.1 ± 1.8 m/s vs. BI-RADS 5: 4.9 ± 2.0 m/s, p = 0.04) and the first peritumoral area (BI-RADS 2/3: 3.4 ± 1.8 m/s vs. BI-RADS 5: 4.3 ± 1.8 m/s, p = 0.003). No significant difference was found between intratumoral gradients (0.03 ± 0.32 m/s vs. 0.0 ± 0.28 m/s; p > 0.999) or gradients across the tumour-tissue interface (-0.17 ± 0.18 m/s vs. -0.13 ± 0.35 m/s; p = 0.202). However, the first peritumoral gradient (-0.16 ± 0.24 m/s vs. -0.35 ± 0.31 m/s; p < 0.0001) and the second peritumoral gradient (-0.11 ± 0.18 m/s vs. -0.22 ± 0.28 m/s; p = 0.037) were significantly steeper in malignant tumours. The AUC was best for PTG1 (0.7358) and PTG2 (0.7039). A threshold value for peritumoral SWI PT1 above 3.76 m/s and for PTG1 below -0.238 m/s·mm-1 indicated malignancy in 90.6% of cases. CONCLUSIONS: Evaluating the peritumoral SWE gradient may improve the diagnostic pre-test probability, as malignant tumours showed a significantly steeper curve of the elasticity values in the peritumoral stroma compared to the linear regression with a relatively flat curve of benign lesions.

Histopathological correlation supports the use of x-rays in the diagnosis of hand osteoarthritis.

OBJECTIVE: To correlate histopathological and radiographic features of distal and proximal interphalangeal (DIP and PIP) joints in order to test whether the use of an x-ray examination would be beneficial to the classification/diagnosis process of hand osteoarthritis (OA). METHODS: DIP and PIP joints were obtained from post mortem specimens (n=40). Plain x-rays of the DIP and PIP joints were taken and radiographic OA was determined by the Kellgren and Lawrence classification. Individual radiographic features were scored according to the method described by Altman. Joint samples were prepared for histological analysis; cartilage damage was graded according to the Mankin scoring system. Spearman's correlation was applied to examine the relationship between histological and radiographical changes. Differences between groups (bony swelling vs no bony swelling) were determined by Student t test. RESULTS: A highly significant correlation was found between histological (Mankin score) and radiographic (Kellgren/Lawrence score) changes in the investigated DIP (r(s)=0.87, p<0.0001) and PIP (r(s)=0.79, p<0.0001) joints. A subgroup of patients (37.5% for DIP and 18.8% for PIP joints) showed advanced radiographic changes (Kellgren/Lawrence score ≥2) in joints without clinical bony swelling. Histologically, the mean Mankin scores accounted for 11±1.66 for DIP and 9.67±2.4 for PIP joints. CONCLUSION: On the basis of histopathological changes of DIP and PIP joints, this investigation demonstrates the validity of x-ray examinations and supports the use of plain radiography in the diagnosis of hand OA and in the classification of hand OA in clinical trials.

Peritumoural Strain Elastography of Newly Diagnosed Breast Tumours: Does Maximum Peritumoural Halo Depth Correlate with Tumour Differentiation and Grade?

To evaluate the diagnostic utility of the maximum ultrasound strain elastography (SE) halo depth in newly diagnosed and histologically confirmed breast lesions, a retrospective study approval was granted by the local Ethical Review Board. Overall, the maximum strain elastography peritumoural halos (SEPHmax)-the maximum distance between the SE stiffening area and the B-mode lesion size-in 428 cases with newly diagnosed breast lesions were retrospectively analysed alongside patient age, affected quadrant, tumour echogenicity, size, acoustic shadowing, and vascularity. Statistical analysis included an ordinary one-way ANOVA to compare the SEPHmax between BI-RADS 2, 3, and 5 groups and between tumour grades 1, 2, and 3. A binary regression analysis was used to determine the correlation between tumour malignancy and the above-mentioned demographic and imaging factors. SEPHmax was significantly higher in BI-RADS 5 tumours (5.5 ± 3.9 mm) compared to BI-RADS 3 (0.9 ± 1.7 mm, p < 0.0001) and 2 (0.6 ± 1.4 mm, p < 0.0001). The receiver operating characteristic area under the curve was 0.933 for the detection of BI-RADS 5 lesions. Furthermore, tumour grades 2 (5.6 ± 3.6 mm, p = 0.001) and 3 (6.8 ± 4.2 mm, p < 0.0001) exhibited significantly higher SEPHmax than grade 1 tumours (4.0 ± 3.9 mm). Similarly, St. Gallen Ki67-stratified low-risk (p = 0.005) and intermediate-risk (p = 0.013) tumours showed smaller SEPHmax than high-risk tumours. Multivariate analysis revealed a significant correlation between malignant differentiation and SEPHmax (standardized regression coefficient 3.17 [95% confidence interval (CI) 2.42-3.92], p < 0.0001), low tumour echogenicity (1.68 [95% CI 0.41-3.00], p = 0.03), and higher patient age (0.89 [95% CI 0.52-1.26], p < 0.0001). High SEPHmax is a strong predictor for tumour malignancy and a higher tumour grade and can be used to improve tumour characterisation before histopathological evaluation. It may also enable radiologists to identify lesions warranting observation rather than immediate biopsy.

The Tomosynthesis Broken Halo Sign: Diagnostic Utility for the Classification of Newly Diagnosed Breast Tumors.

BACKGROUND: Compared to conventional 2D mammography, digital breast tomosynthesis (DBT) offers greater breast lesion detection rates. Ring-like hypodense artifacts surrounding dense lesions are a common byproduct of DBT. This study's purpose was to assess whether minuscule changes spanning this halo-termed the "broken halo sign"-could improve lesion classification. METHODS: This retrospective study was approved by the local ethics review board. After screening 288 consecutive patients, DBT studies of 191 female participants referred for routine mammography with a subsequent histologically verified finding of the breast were assessed. Examined variables included patient age, histological diagnosis, architectural distortion, maximum size, maximum halo depth, conspicuous margins, irregular shape and broken halo sign. RESULTS: While a higher halo strength was indicative of malignancy in general (p = 0.031), the broken halo sign was strongly associated with malignancy (p < 0.0001, odds ratio (OR) 6.33), alongside architectural distortion (p = 0.012, OR 3.49) and a diffuse margin (p = 0.006, OR 5.49). This was especially true for denser breasts (ACR C/D), where the broken halo sign was the only factor predicting malignancy (p = 0.03, 5.22 OR). CONCLUSION: DBT-associated halo artifacts warrant thorough investigation in newly found breast lesions as they are associated with malignant tumors. The "broken halo sign"-the presence of small lines of variable diameter spanning the peritumoral areas of hypodensity-is a strong indicator of malignancy, especially in dense breasts, where architectural distortion may be obfuscated due to the surrounding tissue.

The cutting (w)edge--comparative evaluation of renal baseline biopsies obtained by two different methods.

BACKGROUND: The assessment of donor-derived damage of transplanted kidneys might be instrumental for estimating donor organ quality and for predicting short- and long-term organ outcome. In the present study, we report a new standardized method for obtaining pre-transplant kidney biopsy specimens. Instead of taking wedge biopsies (WBs), a skin punch biopsy (PB) tool was utilized to obtain standardized biopsy samples that also represented deeper cortical zones. METHODS: We compared 147 PB specimens and 114 WBs with respect to the number of glomeruli and arterial vessels they contained. The performance of the two biopsy methods in detecting glomerular damage, interstitial fibrosis/tubular atrophy (IF/TA) and arteriosclerosis was determined by evaluation of subsequent transplant core biopsies of the patients. Statistical comparison employed Kruskal-Wallis and kappa (κ) tests. RESULTS: Significantly more PB samples (89%) than WBs (66%) were diagnostically adequate according to the Banff criteria. Despite a higher number of glomeruli in WBs (34.6 versus 21.7 in punch biopsies), arteries were present in only 68% of WBs but could be found in 93% of punch biopsies. The comparison of findings in pre-transplant biopsies with lesions in corresponding post-transplant core biopsies revealed a superior diagnostic concordance for IF/TA and arteriosclerosis for punch biopsies than for WBs, reaching kappa values of 0.823 versus 0.729 and 0.661 versus 0.516, respectively. CONCLUSION: The use of skin PB tools for obtaining baseline biopsies from transplanted kidneys is a safe and effective method for assessment of donor-derived damage of the organ.