Reliability and Concurrent Validity of the Four Square Step Test in Osteoarthritic Knee Patients

Research has demonstrated reduced dynamic standing balance in people with knee osteoarthritis, but reliable studies appropriate for clinical use have not been assessed. This study looked to assess the validity and reliability of the Four Square Step Test in patients with knee osteoarthritis. A randomised observational, repeated measures study design for inter-rater and intra-rater reliability was completed in men and women with knee osteoarthritis (N=62). In this cohort study, patients completed a baseline assessment including the Four Square Step Test, Berg Balance Scale and Figure of 8 Walk Test, and returned within a four-week period to be reassessed to determine the inter and intra-rater reliability of the Four Square Step Test. The Four Square Step Test, F8W, and Berg Balance Scale were shown to have significant concurrent validity (p < .001, r= 0.803, 0.838, and -0.777 respectively). Over a four-week period intra-raterreliability the Four Square Step Test was significantly reliable (ICC=0.89, lower 95% CI = 0.809). The Four Square Step Test displayed optimal inter-rater reliability between two assessors during assessment two (ICC = 0.983, lower 95% CI = 0.976). The FSST has been shown to be an appropriate measure of dynamic standing balance in knee osteoarthritis patients and is recommended for clinical use

Breast cancer detected and missed by screen-film and digital screening mammography: Studies on trends in classification and surgical treatment in the south of the Netherlands since 1997

__Abstract__ o The specific aims of this thesis are to describe the trends in the diagnosis of advanced breast cancer, the trends in the use of biopsies and surgical management and to explore the effects of the introduction of digital mammography in breast cancer screening. The majority of the advanced breast cancers detected at biennial screening cannot be prevented. In order to obtain a modest reduction of the risk of detecting breast cancer in an advanced stage, efforts are needed to minimize the number of women with an extended screening interval. Quality control in hospitals treating breast cancer patients is important in order to ensure optimal care for women diagnosed with breast cancer. Surgeons performing breast conserving surgery should try to pre-operatively identify patients with a high risk of positive resection margins, especially focusing on the role of microcalcifications since these are more commonly encountered in a screened population. Furthermore, continuous efforts should be made to improve the quality of the excision of non-palpable tumours. In the South of the Netherlands, digital mammography significantly increased the referral rate and cancer detection rate, at the expense of a lower positive predictive value of referral and biopsy. Digital mammography results in a significantly higher cancer detection rate, but programme sensitivity was similar for both screen-film and digital mammography screening

Prediction of adenomyosis diagnosis based on MRI

ObjectiveDevelopment of a multivariate prediction model based on MRI and clinical parameters for histological adenomyosis diagnosis.Materials and methodsThis single centre retrospective cohort study took place in the gynaecological department of a referral hospital. In all, 296 women undergoing hysterectomy with preoperative pelvic MRI between 2007–2022 were included. MRI scans were retrospectively assessed for adenomyosis markers (junctional zone [JZ] parameters, high signal intensity [HSI] foci in a blinded fashion. A multivariate regression model for histopathological adenomyosis diagnosis was developed based on MRI and clinical variables from univariate analysis with p &lt; 0.1 and factors deemed clinically relevant.Results131/296 women (44.3%) had histopathological adenomyosis. Patients had comparable age at hysterectomy, BMI and clinical symptoms, p &gt; 0.05. Adenomyosis patients more often had: undergone a curettage (22.1% vs. 8.9%, p = 0.002), a higher mean JZ thickness (9.40 vs. 8.35 mm, p &lt; .001), maximal JZ thickness (16.00 vs. 13.40 mm, p &lt; .001), mean JZ/myometrium ratio (0.56 vs. 0.49, p = .040), and JZ differential (8.60 vs. 8.15 mm, p = .003). Presence of HSI foci was the strongest predictor for adenomyosis (39.7% vs. 8.9%, p &lt; .001). Based on the parameters age and BMI, history of curettage, dysmenorrhoea, abnormal uterine bleeding (AUB), mean JZ, JZ differential ≥ 5 mm, JZ/myometrium ratio &gt; 40, and presence of HSI foci, a predictive model was created with a good area under the curve (AUC) of .776.ConclusionsThis is the first study to create a diagnostic tool based on MRI and clinical parameters for adenomyosis diagnosis. After sufficient external validation, this model could function as a useful clinical decision-making tool in women with suspected adenomyosis

Prediction of adenomyosis diagnosis based on MRI

ObjectiveDevelopment of a multivariate prediction model based on MRI and clinical parameters for histological adenomyosis diagnosis.Materials and methodsThis single centre retrospective cohort study took place in the gynaecological department of a referral hospital. In all, 296 women undergoing hysterectomy with preoperative pelvic MRI between 2007–2022 were included. MRI scans were retrospectively assessed for adenomyosis markers (junctional zone [JZ] parameters, high signal intensity [HSI] foci in a blinded fashion. A multivariate regression model for histopathological adenomyosis diagnosis was developed based on MRI and clinical variables from univariate analysis with p &lt; 0.1 and factors deemed clinically relevant.Results131/296 women (44.3%) had histopathological adenomyosis. Patients had comparable age at hysterectomy, BMI and clinical symptoms, p &gt; 0.05. Adenomyosis patients more often had: undergone a curettage (22.1% vs. 8.9%, p = 0.002), a higher mean JZ thickness (9.40 vs. 8.35 mm, p &lt; .001), maximal JZ thickness (16.00 vs. 13.40 mm, p &lt; .001), mean JZ/myometrium ratio (0.56 vs. 0.49, p = .040), and JZ differential (8.60 vs. 8.15 mm, p = .003). Presence of HSI foci was the strongest predictor for adenomyosis (39.7% vs. 8.9%, p &lt; .001). Based on the parameters age and BMI, history of curettage, dysmenorrhoea, abnormal uterine bleeding (AUB), mean JZ, JZ differential ≥ 5 mm, JZ/myometrium ratio &gt; 40, and presence of HSI foci, a predictive model was created with a good area under the curve (AUC) of .776.ConclusionsThis is the first study to create a diagnostic tool based on MRI and clinical parameters for adenomyosis diagnosis. After sufficient external validation, this model could function as a useful clinical decision-making tool in women with suspected adenomyosis

Failing systemic right ventricle in a patient with dextrocardia and complex congenitally corrected transposition of the great arteries: a case report of successful transvenous cardiac resynchronization therapy

Background Patients with congenitally corrected transposition of the great arteries (ccTGA) are prone to the development of advanced atrio-ventricular block requiring chronic ventricular pacing. The morphological right ventricle (RV) often develops systolic dysfunction as it is unable to withstand the chronic pressure overload it is exposed to when supporting the systemic circulation.Case summary A 56-year-old woman with dextrocardia and complex ccTGA with a history of dual-chamber implantable cardioverter-defibrillator (DDD-ICD, high degree atrio-ventricular-block and syncopal ventricular tachycardia), presented with progressive heart failure and symptomatic atrial arrhythmias. She underwent a successful ablation and concomitant invasive haemodynamic evaluation of potential alternative/biventricular pacing modalities. During biventricular pacing, the QRS narrowed and the systemic RV intraventricular pressure (Dp/Dt) increased with 30%. She underwent a successful transvenous upgrade to cardiac resynchronization therapy (CRT). The electrocardiogram post-implantation showed biventricular capture and patient showed subjective and objective clinical improvement.Discussion Systemic RV dysfunction in ccTGA can be aggravated by chronic pacing-induced dyssynchrony, contributing to progression of heart failure in this patient group. Transvenous CRT is feasible in ccTGA anatomy and may be pursued in order to improve or preserve the functional status of pacing-dependent ccTGA patients. Invasive haemodynamic contractility evaluation can help assess the potential benefit of CRT in patients with complex anatomy.Cardiolog

Segmentation-based Assessment of Tumor-Vessel Involvement for Surgical Resectability Prediction of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options. This research proposes a workflow and deep learning-based segmentation models to automatically assess tumor-vessel involvement, a key factor in determining tumor resectability. Correct assessment of resectability is vital to determine treatment options. The proposed workflow involves processing CT scans to segment the tumor and vascular structures, analyzing spatial relationships and the extent of vascular involvement, which follows a similar way of working as expert radiologists in PDAC assessment. Three segmentation architectures (nnU-Net, 3D U-Net, and Probabilistic 3D U-Net) achieve a high accuracy in segmenting veins, arteries, and the tumor. The segmentations enable automated detection of tumor involvement with high accuracy (0.88 sensitivity and 0.86 specificity) and automated computation of the degree of tumor-vessel contact. Additionally, due to significant inter-observer variability in these important structures, we present the uncertainty captured by each of the models to further increase insights into the predicted involvement. This result provides clinicians with a clear indication of tumor-vessel involvement and may be used to facilitate more informed decision-making for surgical interventions. The proposed method offers a valuable tool for improving patient outcomes, personalized treatment strategies and survival rates in pancreatic cancer

The potential of sodium-glucose cotransporter 2 inhibitors for the treatment of systemic right ventricular failure in adults with congenital heart disease

AimsGiven the compelling evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the conventional heart failure population, SGLT2i deserve exploration in systemic right ventricular (sRV) failure. The initial experience with dapagliflozin in sRV failure patients is described, with a focus on tolerability and short-term effects on clinical outcomes.Methods and resultsTen patients (70% female, median age 50 years [46.5-52]) with symptomatic sRV failure who received dapagliflozin 10 mg per day on top of optimal medical therapy between 04-2021 and 01-2023 were included. Within 4 weeks, no significant changes in blood pressure, electrolytes, or serum glucose occurred. Creatinine and estimated glomerular filtration rate (eGFR) showed a slight decline (88 & PLUSMN; 17 to 97 & PLUSMN; 23 & mu;mol/L, p = 0.036, and 72 & PLUSMN; 14 vs. 66 & PLUSMN; 16 ml/min/1.73m(2), p = 0.020, respectively). At 6 months follow-up (n = 8), median NT-proBNP decreased significantly from 736.6 [589.3-1193.3] to 531.6 [400.8-1018] ng/L (p = 0.012). Creatinine and eGFR recovered to baseline levels. There were no significant changes in echocardiographic systolic sRV or left ventricular function. New York Heart Association class improved significantly in 4 out of 8 patients (p = 0.046), who also showed an improvement in the 6-minute walk test or bicycle exercise test performance. One female patient developed an uncomplicated urinary tract infection. No patients discontinued treatment.ConclusionDapagliflozin was well-tolerated in this small cohort of sRV failure patients. While the early results on the reduction of NT-proBNP and clinical outcome parameters are encouraging, large-scale prospective studies are warranted to thoroughly evaluate the effects of SGLT2i in the growing sRV failure population

Case report of the broad spectrum of late complications in an adult patient with univentricular physiology palliated by the Fontan circulation

Background At the most severe end of the spectrum of congenital heart disease are patients with an univentricular physiology. They comprise a heterogeneous group of congenital heart malformations that have the common characteristic that the cardiac morphology is not equipped for sustaining a biventricular circulation. Case summary Here, we present a case of an adult patient after Fontan palliation, illustrative of the complex clinical course and the broad spectrum of complications that can be encountered during follow-up, highlighting the need for a multidisciplinary approach in the clinical care for these patients. Discussion During the surgical Fontan procedure, the inferior vena cava is connected to the pulmonary circulation, after prior connection of the superior vena cava to the pulmonary arterial circulation. The resulting cavopulmonary connection, thus lacking a subpulmonic ventricle, provides non-pulsatile passive flow of oxygen-poor blood from the systemic venous circulation into the lungs, and the functional monoventricle pumps the oxygen-rich pulmonary venous return blood into the aorta. With an operative mortality of <5% and current 30-year survival rates up to 85%, the adult population of patients with a Fontan circulation is growing. This increase in survival is, however, inevitably accompanied by long-term complications affecting multiple organ systems, resulting in decline in cardiovascular performance. Conclusion For optimal treatment, the evaluation in a multidisciplinary team is mandatory, using the specific expertise of the team members to timely detect and address late complications and to support quality of life.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Enhancing IgA-mediated neutrophil cytotoxicity against neuroblastoma by CD47 blockade

BACKGROUND: Approximately half of the neuroblastoma patients develop high-risk neuroblastoma. Current treatment involves a multimodal strategy, including immunotherapy with dinutuximab (IgG ch14.18) targeting GD2. Despite achieving promising results, the recurrence rate remains high and poor survival persists. The therapeutic efficacy of dinutuximab is compromised by suboptimal activation of neutrophils and severe neuropathic pain, partially induced by complement activation. METHODS: To enhance neutrophil cytotoxicity, IgG ch14.18 was converted to the IgA isotype, resulting in potent neutrophil-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), without complement activation. However, myeloid checkpoint molecules hamper neutrophil cytotoxicity, for example through CD47 that is overexpressed on neuroblastomas and orchestrates an immunosuppressive environment upon ligation to signal regulatory protein alpha (SIRPα) expressed on neutrophils. In this study, we combined IgA therapy with CD47 blockade. RESULTS: In vitro killing assays showed enhanced IgA-mediated ADCC by neutrophils targeting neuroblastoma cell lines and organoids in comparison to IgG. Notably, when combined with CD47 blockade, both IgG and IgA therapy were enhanced, though the combination with IgA resulted in the greatest improvement of ADCC. Furthermore, in a neuroblastoma xenograft model, we systemically blocked CD47 with a SIRPα fusion protein containing an ablated IgG1 Fc, and compared IgA therapy to IgG therapy. Only IgA therapy combined with CD47 blockade increased neutrophil influx to the tumor microenvironment. Moreover, the IgA combination strategy hampered tumor outgrowth most effectively and prolonged tumor-specific survival. CONCLUSION: These promising results highlight the potential to enhance immunotherapy efficacy against high-risk neuroblastoma through improved neutrophil cytotoxicity by combining IgA therapy with CD47 blockade