Rituximab as a First-line Treatment for Autoimmune Hemolytic Anemia in Multicentric Castleman's Disease.

Castleman´s disease (CD) is a rare lymphoproliferative disorder. Concurrent autoimmune disease and CD are uncommon, but even more so, comorbid CD and autoimmune hemolytic anemia (AIHA). To the best of our knowledge, this case represents the first successful AIHA and multicentric CD (MCD) treatment using rituximab as first-line treatment. We present the case of a 53-year-old woman with a 10-year history of plasma cell variant CD who arrived at the emergency department with signs and symptoms of anemia. On admission, we made a preliminary diagnosis of hemolytic anemia and initiated immunosuppressive therapy with rituximab and steroids. After seven days, the patient recovered according to clinical and laboratory parameters, and we discharged her early. We portray a rare occurrence of CD and AIHA successfully treated with rituximab and steroid therapy, which makes our case unique.

Metastatic Hepatoblastoma in Adolescence: A Clinical Case Report and Literature Review.

Hepatoblastoma is the most common hepatic neoplasm in children. However, its incidence is infrequent beyond age five. We present the case of a 15-year-old female diagnosed with metastatic hepatoblastoma during hospitalization for liver function deterioration. The patient presented with abdominal distension, jaundice, and other symptoms indicative of advanced disease. Imaging and biopsy confirmed stage IV epithelial hepatoblastoma with pulmonary metastases. This case underscores the importance of considering hepatoblastoma in older pediatric patients or young adults presenting with hepatic masses despite lacking traditional risk factors for liver malignancies.

An Unexpected Cause of Abdominal Discomfort: Non-pancreatic Mesenteric Pseudocyst.

Mesenteric cysts (MCs), rare entities of embryologic origin, predominantly affect the small bowel's mesentery. The clinical manifestations of MCs often lack specificity, which complicates diagnosis. Given their rarity, detailed reporting of MC cases is essential to enhance understanding and improve treatment strategies. We present a case of a 45-year-old male who presented to the emergency department with a one-month history of abdominal pain in the umbilical region, postprandial fullness, progressive decrease in food intake, 12 kg weight loss, and increased abdominal girth. Computed tomography (CT) imaging revealed a well-defined mass in the jejunoileal area. During the exploratory laparotomy, we identified and excised a fibrotic mass on the mesentery of the ileal jejunum, which was not adherent to the intestines. We discharged the patient with no complications following an uneventful four-day observational period. Histopathological examination, including immunohistochemical staining, confirmed the lesion as a non-pancreatic mesenteric pseudocyst. On the follow-up visit, the patient reported no complications. This case report underscores the solitary, multilocular nature of the jejunoileal MC, distinct for its serosanguineous fluid content. In conclusion, this case highlights the diagnostic challenge of MCs and illustrates the potential for successful management with a timely and multidisciplinary approach.

Hyperpolarized 129Xe MR Spectroscopy in the Lung Shows 1-year Reduced Function in Idiopathic Pulmonary Fibrosis.

Background Idiopathic pulmonary fibrosis (IPF) is a temporally and spatially heterogeneous lung disease. Identifying whether IPF in a patient is progressive or stable is crucial for treatment regimens. Purpose To assess the role of hyperpolarized (HP) xenon 129 (129Xe) MRI measures of ventilation and gas transfer in IPF generally and as an early signature of future IPF progression. Materials and Methods In a prospective study, healthy volunteers and participants with IPF were consecutively recruited between December 2015 and August 2019 and underwent baseline HP 129Xe MRI and chest CT. Participants with IPF were followed up with forced vital capacity percent predicted (FVC%p), diffusing capacity of the lungs for carbon monoxide percent predicted (DLco%p), and clinical outcome at 1 year. IPF progression was defined as reduction in FVC%p by at least 10%, reduction in DLco%p by at least 15%, or admission to hospice care. CT and MRI were spatially coregistered and a measure of pulmonary gas transfer (red blood cell [RBC]-to-barrier ratio) and high-ventilation percentage of lung volume were compared across groups and across fibrotic versus normal-appearing regions at CT by using Wilcoxon signed rank tests. Results Sixteen healthy volunteers (mean age, 57 years ± 14 [SD]; 10 women) and 22 participants with IPF (mean age, 71 years ± 9; 15 men) were evaluated, as follows: nine IPF progressors (mean age, 72 years ± 7; five women) and 13 nonprogressors (mean age, 70 years ± 10; 11 men). Reduction of high-ventilation percent (13% ± 6.1 vs 8.2% ± 5.9; P = .03) and RBC-to-barrier ratio (0.26 ± 0.06 vs 0.20 ± 0.06; P = .03) at baseline were associated with progression of IPF. Participants with progressive disease had reduced RBC-to-barrier ratio in structurally normal-appearing lung at CT (0.21 ± 0.07 vs 0.28 ± 0.05; P = .01) but not in fibrotic regions of the lung (0.15 ± 0.09 vs 0.14 ± 0.04; P = .62) relative to the nonprogressive group. Conclusion In this preliminary study, functional measures of gas transfer and ventilation measured with xenon 129 MRI and the extent of fibrotic structure at CT were associated with idiopathic pulmonary fibrosis disease progression. Differences in gas transfer were found in regions of nonfibrotic lung. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gleeson and Fraser in this issue.

Activity-Oriented Antiedema Proprioceptive Therapy (TAPA) for Shoulder Mobility Improvement in Women with Upper Limb Lymphedema Secondary to Breast Cancer: A Multicenter Controlled Clinical Trial.

BACKGROUND: Lymphedema, secondary to breast cancer (BCRL), is the abnormal accumulation of protein-rich fluid in the interstitium caused by a malfunction of the lymphatic system. It causes swelling, deficiencies in upper limb functions and structures, sensory pain and emotional alterations, which have a chronic course and affect the upper limb's functionality. This study aims to verify the efficacy and efficiency in the upper limb´s functionality of a protocolized experimental approach based on occupational therapy, TAPA (activity-oriented proprioceptive antiedema therapy), in the rehabilitation of BCRL in stages I and II, comparing it with the conservative treatment considered as the standard, complex decongestive therapy (CDT), through a multicenter randomized clinical trial. METHODS: a randomized and prospective clinical trial was conducted with experimental and control groups. Women diagnosed with BCRL belonging to institutions in Córdoba and Aragon (Spain) participated. Sociodemographic variables and those related to the functionality of the affected upper limb were evaluated before and after the intervention. RESULTS: The results showed statistically significant differences in the analysis of covariance performed for the variable joint balance of the shoulder´s external rotation (p = 0.045) that could be attributed to the intervention performed; however, the effect size was minimal (η2 ≤ 0.080). In the rest of the variables, no significant differences were found. CONCLUSIONS: TAPA may be an alternative to the conservative treatment of women with BCRL. It was shown to be just as effective for volume reduction and activity performance as CDT but more effective in improving external rotation in shoulder joint balance.

Impact of Activity-Oriented Propioceptive Antiedema Therapy on the Health-Related Quality of Life of Women with Upper-Limb Lymphedema Secondary to Breast Cancer-A Randomized Clinical Trial.

BACKGROUND: Alterations derived from lymphedema in the upper-limb secondary to breast cancer-related lymphedema (BCRL) decrease the health-related quality of life (HRQoL), but there is limited evidence of the impact of the different interventions on it. The aim of this research was to compare the effect of conventional treatment with another treatment based on Activity-Oriented Antiedema Proprioceptive Therapy (TAPA) on HRQoL in women diagnosed with BCRL. METHODS: A prospective clinical study was designed with two parallel arms. The study population consisted of women diagnosed with BCRL in stage I and II, belonging to different institutions in Córdoba and Aragon, Spain. Sociodemographic and HRQoL-related variables, pain, tightness, heaviness and functionality were obtained before and after treatments. RESULTS: 51 women participated in the study, 25 received the conventional treatment and 26 the TAPA, with a mean age of 59.24 ± 9.55 years. HRQoL was significantly related to upper-limb function and pain on the participants' affected side. In addition, covariance analysis (ANCOVA) showed that the TAPA treatment interfered less in the performance of activities of daily life and produced significant improvements in the social dimension of HRQoL. CONCLUSIONS: the non-use of compressive elements in the rehabilitative treatment of the BCRL that is proposed with TAPA improves aspects such as self-image and participation in social and recreational activities.

Dynamic contrast enhanced MRI for the evaluation of lung perfusion in idiopathic pulmonary fibrosis.

BACKGROUND: The objective of this work was to apply quantitative and semiquantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) methods to evaluate lung perfusion in idiopathic pulmonary fibrosis (IPF). METHODS: In this prospective trial 41 subjects, including healthy control and IPF subjects, were studied using DCE-MRI at baseline. IPF subjects were then followed for 1 year; progressive IPF (IPFprog) subjects were distinguished from stable IPF (IPFstable) subjects based on a decline in percent predicted forced vital capacity (FVC % pred) or diffusing capacity of the lung for carbon monoxide (D LCO % pred) measured during follow-up visits. 35 out of 41 subjects were retained for final baseline analysis (control: n=15; IPFstable: n=14; IPFprog: n=6). Seven measures and their coefficients of variation (CV) were derived using temporally resolved DCE-MRI. Two sets of global and regional comparisons were made: control versus IPF groups and control versus IPFstable versus IPFprog groups, using linear regression analysis. Each measure was compared with FVC % pred, D LCO % pred and the lung clearance index (LCI % pred) using a Spearman rank correlation. RESULTS: DCE-MRI identified regional perfusion differences between control and IPF subjects using first moment transit time (FMTT), contrast uptake slope and pulmonary blood flow (PBF) (p≤0.05), while global averages did not. FMTT was shorter for IPFprog compared with both IPFstable (p=0.004) and control groups (p=0.023). Correlations were observed between PBF CV and D LCO % pred (rs= -0.48, p=0.022) and LCI % pred (rs= +0.47, p=0.015). Significant group differences were detected in age (p<0.001), D LCO % pred (p<0.001), FVC % pred (p=0.001) and LCI % pred (p=0.007). CONCLUSIONS: Global analysis obscures regional changes in pulmonary haemodynamics in IPF using DCE-MRI in IPF. Decreased FMTT may be a candidate marker for IPF progression.

Opportunistic detection of atrial fibrillation in subjects aged 65 years or older in primare care: a randomised clinical trial of efficacy. DOFA-AP study protocol.

BACKGROUND: Clinical Practice Guidelines recommend using peripheral blood pulse measuring as a screening test for Atrial Fibrillation. However, there is no adequate evidence supporting the efficacy of such procedure in primary care clinical practice. This paper describes a study protocol designed to verify whether early opportunistic screening for Atrial Fibrillation by measuring blood pulse is more effective than regular practice in subjects aged 65 years attending primary care centers. METHODS/DESIGN: An cluster-randomized controlled trial conducted in Primary Care Centers of the Spanish National Health Service. A total of 269 physicians and nurses will be allocated to one of the two arms of the trial by stratified randomization with a 3:2 ratio (three practitioners will be assigned to the Control Group for every two practitioners assigned to the Experimental Group). As many as 12 870 patients aged 65 years or older and meeting eligibility criteria will be recruited (8 580 will be allocated to the Experimental Group and 4 290 to the Control Group). Randomization and allocation to trial groups will be carried out by a central computer system. The Experimental Group practitioners will conduct an opportunistic case finding for patients with Atrial Fibrillation, while the Control Group practitioners will follow the regular guidelines. The first step will be finding new Atrial Fibrillation cases. A descriptive inferential analysis will be performed (bivariate and multivariate by multilevel logistic regression analysis). DISCUSSION: If our hypothesis is confirmed, we expect Primary Care professionals to take a more proactive approach and adopt a new protocol when a patient meeting the established screening criteria is identified. Finally, we expect this measure to be incorporated into Clinical Practice Guidelines. TRIAL REGISTRATION: The study is registered as NCT01291953 (ClinicalTrials.gob).

Markovian chemicals "in silico" design (MARCH-INSIDE), a promising approach for computer-aided molecular design I: discovery of anticancer compounds.

A simple stochastic approach, designed to model the movement of electrons throughout chemical bonds, is introduced. This model makes use of a Markov matrix to codify useful structural information in QSAR. The self-return probabilities of this matrix throughout time ((SR)pi(k)) are then used as molecular descriptors. Firstly, a calculation of (SR)pi(k) is made for a large series of anticancer and non-anticancer chemicals. Then, k-Means Cluster Analysis allows us to split the data series into clusters and ensure a representative design of training and predicting series. Next, we develop a classification function through Linear Discriminant Analysis (LDA). This QSAR discriminates between anticancer compounds and non-active compounds with a correct global classification of 90.5% in the training series. The model also correctly classified 86.07% of the compounds in the predicting series. This classification function is then used to perform a virtual screening of a combinatorial library of coumarins. In this connection, the biological assay of some furocoumarins, selected by virtual screening using the present model, gives good results. In particular, a tetracyclic derivative of 5-methoxypsoralen (5-MOP) has an IC50 against HL-60 tumoral line around 6 to 10 times lower than those for 8-MOP and 5-MOP (reference drugs), respectively. Finally, application of Iso-contribution Zone Analysis (IZA) provides structural interpretation of the biological activity predicted with this QSAR.