Prevalence of Findings in Routine Abdominal Ultrasound in Patients with Systemic Autoimmune Rheumatic Diseases and Their Impact on Therapeutic Decision Making

Patients with systemic autoimmune rheumatic diseases (SARD) often receive abdominal ultrasound examinations to screen for organ involvement; yet, the spectrum of findings and their clinical relevance are poorly understood. We conducted a retrospective chart review of inpatients from a rheumatological referral centre with an abdominal ultrasound between 1 January2006 and 31 December 2015, examining 1092 SARD patients with a total of 1695 inpatient stays. The mean age was 55.1 years (range: 17–90 years, SD: 15.8), and the mean disease duration was 6.4 years (range: 0.0–52.8 years, SD: 9.1). A total of 87.5% of the patients were female. The most frequent ultrasound findings were hepatic steatosis (in 26.8% of all patients), splenomegaly (15.2% of all patients), pancreatic lipomatosis (14.3% of all patients) and aortic sclerosis (13.9% of all patients). Based on glucocorticoid and disease-modifying antirheumatic drug use, we identified cases where immuno-modulatory medication was escalated; there was an association between therapy escalation and the findings of hepatomegaly and pleural effusion (as tested via Fisher’s exact test). In patients with several examinations during the defined time span (n = 318), we found ultrasound findings to change, especially findings of hepatomegaly, pleural effusion and splenomegaly. When justifying decisions regarding the further treatment of a patient in the discharge letter, abdominal ultrasound results were rarely discussed. Abdominal ultrasound rarely yielded disease-specific or treatment-changing results.

Confirming a Historical Diagnosis of Multiple Sclerosis: Challenges and Recommendations

Patients with a historical diagnosis of multiple sclerosis (MS) — a patient presenting with a diagnosis of MS made previously and by a different clinician — present specific diagnostic and therapeutic challenges in clinical practice. Application of the McDonald criteria is most straightforward when applied contemporaneously with a syndrome typical of an MS attack or relapse; however, retrospective application of the criteria in some patients with a historical diagnosis of MS can be problematic. Limited patient recollection of symptoms and evolution of neurological examination and MRI findings complicate confirmation of an earlier MS diagnosis and assessment of subsequent disease activity or clinical progression. Adequate records for review of prior clinical examinations, laboratory results, and/or MRI scans obtained at the time of diagnosis or during ensuing care may be inadequate or unavailable. This paper provides recommendations for a clinical approach to the evaluation of patients with a historical diagnosis of MS to aid diagnostic confirmation, avoid misdiagnosis, and inform therapeutic decision-making.

An Integrated Epigenomic and Genomic View on Phyllodes and Phyllodes-Like Breast Tumors

Fibroepithelial lesions (FL) of the breast, in particular Phyllodes tumors (PT) and fibroadenomas, pose a significant diagnostic challenge. There are no generally accepted criteria that distinguish benign, borderline, malignant PT, and FA. Combined genome-wide DNA methylation and copy number variant (CNV) profiling is an emerging strategy to classify tumors. We compiled a series of patient-derived archival biopsy specimens reflecting the FL spectrum and histological mimickers including clinical follow-up data. DNA methylation and CNVs were determined by well-established microarrays. Comparison of the patterns with a pan-cancer dataset assembled from public resources including "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) suggests that FLs form a methylation class distinct from both control breast tissue as well as common breast cancers. Complex CNVs were enriched in clinically aggressive FLs. Subsequent fluorescence in situ hybridization (FISH) analysis detected respective aberrations in the neoplastic mesenchymal component of FLs only, confirming that the epithelial component is non-neoplastic. Of note, our approach could lead to the elimination of the diagnostically problematic category of borderline PT and allow for optimized prognostic patient stratification. Furthermore, the identified recurrent genomic aberrations such as 1q gains (including MDM4), CDKN2a/b deletions and EGFR amplifications may inform therapeutic decision-making.

Empowering Patients in the Therapeutic Decision-Making Process: A Glance Into Behçet's Syndrome

Behçet's syndrome (BS) represents a challenging condition, characterized by a variable spectrum of disease profile and associated with a significant limitation of the daily activities as well as a potential negative impact on relationships and psychological status. Considering also the complexity of the therapeutic management of BS, that often includes biological off-label treatments, the participation in the therapeutic decision-making process of the BS patients is essential to ensure the integration of the care process into the life of the patient. For this reason, the empowerment of BS patients represents a crucial need and the present work is aimed at fully exploring all the potential variables implicated in the BS patient empowerment, also highlighting major points to consider and concrete actions to be planned in the immediate future in order to implement a pragmatic facilitation of the patients' empowerment.

Diagnosis and therapeutic decision-making for the neutropenic patient

Determining the cause of a low neutrophil count in a pediatric or adult patient is essential for the hematologist's clinical decision-making. Fundamental to this diagnostic process is establishing the presence or lack of a mature neutrophil storage pool, as absence places the patient at higher risk for infection and the need for supportive care measures. Many diagnostic tests, eg, a peripheral blood smear and bone marrow biopsy, remain important tools, but greater understanding of the diversity of neutropenic disorders has added new emphasis on evaluating for immune disorders and genetic testing. In this article, a structure is provided to assess patients based on the mechanism of neutropenia and to prioritize testing based on patient age and hypothesized pathophysiology. Common medical quandaries including fever management, need for growth factor support, risk of malignant transformation, and curative options in congenital neutropenia are reviewed to guide medical decision-making in neutropenic patients.

Analysis of metabolomic and genomic markers for diagnosing cardiovascular diseases

Cardiovascular disease is the leading cause of death in the population. Unfortunately, cardiovascular disease and its associated risks are often difficult to diagnose due to the many factors associated with age and other comorbidities that lead to significant uncertainty in diagnostic classification and therapeutic decision making. Therefore, there is a great need to find new biomarkers for more accurate diagnosis, risk assessment and treatment recommendations for both acute and chronic cardiovascular disease. This article presents an analysis of metabolomic and genomic markers used for the diagnosis of cardiovascular disease. The study of the metabolome in combination with the genome and proteome can provide important information about both the pathogenesis of cardiovascular disease and the ability to search for and identify new cardiovascular disease biomarkers. Along with the fundamental data on new cardiovascular disease biomarkers, there is an urgent need for further research confirming their great potential for practical health care.

Role of barium enema examination for the diagnosis of submucosal invasion depth in T1 colorectal cancers

Background The indication for endoscopic resection for submucosally invasive colorectal cancer (T1-CRC) depends on the preoperative diagnosis of invasion depth. The aim of this investigation was to evaluate the association between barium enema examination (BE) profile views and depth of submucosal (SM) invasion in CRCs. Methods We reviewed the radiographic and endoscopic findings of 145 T1-CRCs diagnosed from 2008 to 2019. We measured the widths of horizontal and vertical rigidity under a BE profile view corresponding to CRC and compared the values with SM invasion depth. Horizontal rigidity was defined as the horizontal length and vertical rigidity as the vertical width of the barium defect corresponding to each target lesion. The most appropriate cut-off values for predicting SM invasion ≥1.8 mm were calculated by receiver operating characteristic curve analysis. Results Values of horizontal rigidity (r = 0.626, P < 0.05) and vertical rigidity (r = 0.482, P < 0.05) correlated significantly with SM invasion depth. The most appropriate cut-off values for the prediction of SM invasion depth ≥ 1.8 mm were 4.5 mm for horizontal rigidity, with an accuracy of 80.7%; and 0.7 mm for vertical rigidity, with an accuracy of 77.9%. The prevalence of lympho-vascular invasion was significantly different when those cut-off values were applied (43.2% vs. 17.5% for horizontal rigidity, P < 0.005). Conclusions In T1-CRC, values of horizontal and vertical rigidities under a BE profile view were correlated with SM invasion depth. While the accuracy of the rigidities for the prediction of SM invasion depth ≥ 1.8 mm was not high, horizontal rigidity may be predictive of lympho-vascular invasion, thus aiding in therapeutic decision-making.

The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics

Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conduct whole-exome sequencing and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histology. A median of 68.9% of point mutations and 83% of copy number aberrations are shared between different histologic components within the same tumors. Furthermore, different histologic components within the tumors demonstrate similar subclonal architecture. On the other hand, transcriptomic profiling reveals shared pathways between the same histologic subtypes from different patients, which is supported by the analyses of the transcriptomic data from 141 cell lines and 343 lung cancers of different histologic subtypes. These data derived from mixed histologic subtypes in the setting of identical genetic background and exposure history support that the histologic fate of lung cancer cells is associated with transcriptomic features rather than the genomic profiles in most tumors.

Experiences in treatment of multiple sclerosis with natalizumab from a real-life cohort over 15 years

Natalizumab (NTZ) has been used for treatment of highly active relapsing–remitting multiple sclerosis (MS). When stopping NTZ the risk of severe rebound phenomenon has to be considered. We aimed to investigate the use of NTZ in clinical routine and focused on identification of potential risk factors for disease reactivation after treatment discontinuation. At the Medical University of Innsbruck, Austria, we identified all MS patients who were treated with NTZ and performed a retrospective analysis on therapeutic decision making, disease course before, during and after treatment with NTZ and on risk factors for disease reactivation after NTZ discontinuation. 235 NTZ treated MS patients were included, of whom 105 had discontinued treatment. At NTZ start disease duration was 5.09 (IQR 2.09–10.57) years, average number of total relapses was 4 (IQR 3–6) and median EDSS 2.0 (range 0–6.5), whereby these values significantly decreased over time. Reduction of annualized relapse rate (ARR) on treatment was 93% and EDSS remained stable in 64%. In multivariate regression models only conversion to secondary progressive MS (SPMS) on treatment was significantly associated with lower risk of disease reactivation after NTZ, while ARR before treatment was associated with earlier disease reactivation. We could confirm the high therapeutic efficacy of NTZ which trends to be used earlier in the disease course nowadays. Discontinuation of NTZ seems safe only in patients who convert to SPMS during treatment, while higher ARR before NTZ increases the risk of disease reactivation after treatment discontinuation.

Sagittal balance: from theory to clinical practice

Adequate sagittal balance (SB) is essential to maintain an upright, efficient, and painless posture. It has been shown that sagittal profile alterations affect quality of life of patients with a similar or even greater impact than chronic disease. Evaluation of the SB has gained much relevance in recent years, with recognition of its importance in the evaluation of spinal pathology. This review summarizes the basic principles of SB, aiming to obtain a practical, simple and understandable evaluation of the sagittal profile of a patient. SB is a dynamic process that involves a varying degree of energy expenditure. Distinguishing between a balanced, compensated imbalance or decompensated imbalanced patient, is relevant to diagnosis and therapeutic decision-making. Cite this article: EFORT Open Rev 2021;6:1193-1202. DOI: 10.1302/2058-5241.6.210062