scholarly journals Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1969
Author(s):  
Aline Rangel-Pozzo ◽  
Pak Yu ◽  
Sadhana LaL ◽  
Yasmin Asbaghi ◽  
Luiza Sisdelli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Genomic Instability ◽  
Clinical Decision Making ◽  
Three Dimensional ◽  
Clinical Decision ◽  
Response To Treatment ◽  
Average Intensity ◽  
Patient Response ◽  
Smoldering Multiple Myeloma

The prognosis of multiple myeloma (MM), an incurable B-cell malignancy, has significantly improved through the introduction of novel therapeutic modalities. Myeloma prognosis is essentially determined by cytogenetics, both at diagnosis and at disease progression. However, for a large cohort of patients, cytogenetic analysis is not always available. In addition, myeloma patients with favorable cytogenetics can display an aggressive clinical course. Therefore, it is necessary to develop additional prognostic and predictive markers for this disease to allow for patient risk stratification and personalized clinical decision-making. Genomic instability is a prominent characteristic in MM, and we have previously shown that the three-dimensional (3D) nuclear organization of telomeres is a marker of both genomic instability and genetic heterogeneity in myeloma. In this study, we compared in a longitudinal prospective study blindly the 3D telomeric profiles from bone marrow samples of 214 initially treatment-naïve patients with either monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or MM, with a minimum follow-up of 5 years. Here, we report distinctive 3D telomeric profiles correlating with disease aggressiveness and patient response to treatment in MM patients, and also distinctive 3D telomeric profiles for disease progression in smoldering multiple myeloma patients. In particular, lower average intensity (telomere length, below 13,500 arbitrary units) and increased number of telomere aggregates are associated with shorter survival and could be used as a prognostic factor to identify high-risk SMM and MM patients.

Biomechanical and clinical outcomes in response to inpatient multidisciplinary hip and groin rehabilitation in UK military personnel

2021 ◽  
pp. bmjmilitary-2020-001588
Author(s):  
Richard Allan ◽  
R P Cassidy ◽  
R J Coppack ◽  
T Papadopoulou ◽  
A N Bennett
Keyword(s):  
Clinical Outcomes ◽  
Clinical Decision Making ◽  
Three Dimensional ◽  
Inpatient Rehabilitation ◽  
Clinical Decision ◽  
Patient Reported Outcome Measures ◽  
Service Evaluation ◽  
Response To Treatment ◽  
Military Population ◽  
Patient Reported

IntroductionHip and groin related pain is a common complaint among the military population across UK Defence Rehabilitation and addressing associated biomechanical dysfunction is a key treatment goal. Personnel are exposed to complex occupational loads, therefore assessing movement during demanding tasks may expose biomechanical deficits. Observing biomechanical and clinical outcomes in response to treatment is therefore an important consideration. The aims were to examine clinical and biomechanical outcomes prior to (T1) and 12 weeks post (T2) inpatient rehabilitation and explore the influence of pathological subgroup.MethodsProspective cohort study as part of a clinical service evaluation of 25 patients undergoing treatment for hip and groin related pain. Three-dimensional motion capture (3DM) during a single-leg squat, hip strength and patient-reported outcome measures were collected at T1 and T2.ResultsIncreased abductor and external rotator strength with reductions in contralateral pelvic drop (1.9°; p=0.041) at T2 on the injured side. Pain reduced by 9.6 mm (p=0.017) but no differences were found for Non-Arthritic Hip Score (NAHS). No statistically significant differences were found between pathological subgroups. Kinematic profiles display variation between diagnostic subgroups and response to treatment.ConclusionStrength and pain improved with treatment in this service evaluation although biomechanical adaptation and NAHS remain inconclusive. Small and uneven sample size prevents a firm conclusion regarding the effect of pathological subgroupings, however, the data can be considered hypothesis generating for future, larger studies to integrate 3DM for monitoring response to rehabilitation in pathological subgroups to support clinical decision making.

scholarly journals Challenges in treatment of renal echinococcosis with gross hydatiduria and unsalvageable kidney: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Sameera Shuaibi ◽  
Abdelrahman AlAshqar ◽  
Munirah Alabdulhadi ◽  
Wasl Al-Adsani
Keyword(s):  
Clinical Decision Making ◽  
Scientific Evidence ◽  
Renal Involvement ◽  
Clinical Decision ◽  
Response To Treatment ◽  
Standards Of Care ◽  
Future Research ◽  
Positive Serology ◽  
Grape Skin

Abstract Introduction Renal echinococcosis is of rare occurrence, and although often asymptomatic, it can present with various mild to drastic presentations, of which hydatiduria is pathognomonic. Diagnosis can be preliminarily established by imaging, and treatment is primarily surgical. We present a patient with renal echinococcosis treated successfully with exclusive antiparasitic pharmacotherapy after refusing surgery despite extensive renal involvement. We hope through this report to help establish future solid guidelines regarding this uncommon therapeutic approach. Case presentation This is a case of a 49-year-old Syrian shepherd presenting with flank pain and passage of grape-skin-like structures in urine. A diagnosis of renal echinococcosis with hydatiduria and significant parenchymal destruction was established based on exposure history, positive serology, imaging findings, and renal scintigraphy. After proper counseling, the patient refused nephrectomy and was therefore started on dual pharmacotherapy (albendazole and praziquantel) and is having an uneventful follow-up and a satisfactory response to treatment. Conclusion This case embodies the daily challenges physicians navigate as they uphold the ethical principles of their practice and support their patients’ autonomy while delivering the best standards of care and consulting the scientific evidence. Although surgery is the cornerstone of renal echinococcosis treatment, treating physicians should be prepared to tackle situations where surgery cannot be done and offer the best next available option for patients who refuse surgery. As data on exclusive pharmacotherapy are limited, future research should thoroughly investigate the efficacy of this uncommon approach and outline reliable recommendations, facilitating future clinical decision-making in this avenue.

scholarly journals Treatment Discontinuation and Disease Progression with Injectable Disease-Modifying Therapies

2013 ◽  
Vol 15 (4) ◽  
pp. 194-201 ◽  
Author(s):  
Robert J. Fox ◽  
Amber R. Salter ◽  
Tuula Tyry ◽  
Jennifer Sun ◽  
Xiaojun You ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Clinical Decision Making ◽  
Medication Compliance ◽  
Clinical Decision ◽  
Research Committee ◽  
The North ◽  
Disease Modifying Therapies ◽  
Patient Reported ◽  
Disease Modifying

Injectable first-line disease-modifying therapies (DMTs) for multiple sclerosis (MS) are generally prescribed for continuous use. Accordingly, the various factors that influence patient persistence with treatment and that can lead some patients to switch medications or discontinue treatment may affect clinical outcomes. Using data from the North American Research Committee on Multiple Sclerosis (NARCOMS) database, this study evaluated participants' reasons for discontinuation of injectable DMTs as well as the relationship between staying on therapy and sustained patient-reported disease progression and annualized relapse rates. Participants selected their reason(s) for discontinuation from among 16 possible options covering the categories of efficacy, safety, tolerability, and burden, with multiple responses permitted. Both unadjusted data and data adjusted for baseline age, disease duration, disability, and sex were evaluated. Discontinuation profiles varied among DMTs. Participants on intramuscular interferon beta-1a (IM IFNβ-1a) and glatiramer acetate (GA) reported the fewest discontinuations based on safety concerns, although GA was associated with reports of higher burden and lower efficacy than other therapies. Difficulties with tolerability were more often reported as a reason for discontinuing subcutaneous (SC) IFNβ-1a than as a reason for discontinuing IM IFNβ-1a, GA, or SC IFNβ-1b. In the persistent therapy cohort, less patient-reported disability progression was reported with IM IFNβ-1a treatment than with SC IFNβ-1a, IFNβ-1b, or GA. These findings have relevance to clinical decision making and medication compliance in MS patient care.

Right ventricle and pulmonary arterial pressure

2016 ◽  
Author(s):  
Annemien E. van den Bosch ◽  
Luigi P. Badano ◽  
Julia Grapsa
Keyword(s):  
Clinical Decision Making ◽  
Complex Geometry ◽  
Three Dimensional ◽  
Clinical Decision ◽  
Tissue Doppler ◽  
Left Ventricular ◽  
Doppler Imaging ◽  
Prognostic Information ◽  
Recent Developments ◽  
And Function

Right ventricular (RV) performance plays an important role in the morbidity and mortality of patients with left ventricular dysfunction, congenital heart disease, and pulmonary hypertension. Assessment of RV size, function, and haemodynamics has been challenging because of its complex geometry. Conventional two-dimensional echocardiography is the modality of choice for assessment of RV function in clinical practice. Recent developments in echocardiography have provided several new techniques for assessment of RV dimensions and function, include tissue Doppler imaging, speckle-tracking imaging, and volumetric three-dimensional imaging. However, specific training, expensive dedicated equipment, and extensive clinical validation are still required. Doppler methods interrogating tricuspid inflow and pulmonary artery flow velocities, which are influenced by changes in pre- and afterload conditions, may not provide robust prognostic information for clinical decision-making. This chapter addresses the role of the various echocardiographic modalities used to assess the RV and pulmonary circulation. Special emphasis has been placed on technical considerations, limitations, and pitfalls of image acquisition and analysis.

scholarly journals Clinical value of measurable residual disease testing for assessing depth, duration, and direction of response in multiple myeloma

2020 ◽  
Vol 4 (14) ◽  
pp. 3295-3301
Author(s):  
Joaquin Martinez-Lopez ◽  
Sandy W. Wong ◽  
Nina Shah ◽  
Natasha Bahri ◽  
Kaili Zhou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Decision Making ◽  
Residual Disease ◽  
Clinical Care ◽  
Progression Free Survival ◽  
Clinical Decision ◽  
Routine Practice ◽  
Clinical Value ◽  
The Impact ◽  
Measurable Residual Disease

Abstract Few clinical studies have reported results of measurable residual disease (MRD) assessments performed as part of routine practice. Herein we present our single-institution experience assessing MRD in 234 multiple myeloma (MM) patients (newly diagnosed [NDMM = 159] and relapsed [RRMM = 75]). We describe the impact of depth, duration, and direction of response on prognosis. MRD assessments were performed by next-generation sequencing of immunoglobulin genes with a sensitivity of 10−6. Those achieving MRD negativity at 10−6, as well as 10−5, had superior median progression-free survival (PFS). In the NDMM cohort, 40% of the patients achieved MRD negativity at 10−6 and 59% at 10−5. Median PFS in the NDMM cohort was superior in those achieving MRD at 10−5 vs <10−5 (PFS: 87 months vs 32 months; P < .001). In the RRMM cohort, 36% achieved MRD negativity at 10−6 and 47% at 10−5. Median PFS was superior for the RRMM achieving MRD at 10−5 vs <10−5 (PFS: 42 months vs 17 months; P < .01). Serial MRD monitoring identified 3 categories of NDMM patients: (A) patients with ≥3 MRD 10−6 negative samples, (B) patients with detectable but continuously declining clonal numbers, and (C) patients with stable or increasing clonal number (≥1 log). PFS was superior in groups A and B vs C (median PFS not reached [NR], NR, 55 respectively; P < .001). This retrospective evaluation of MRD used as part of clinical care validates MRD as an important prognostic marker in NDMM and RRMM and supports its use as an endpoint in future clinical trials as well as for clinical decision making.

Interrogating metastatic prostate cancer treatment switch decisions.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 296-296
Author(s):  
David Lorente ◽  
Praful Ravi ◽  
Niven Mehra ◽  
Carmel Jo Pezaro ◽  
Aurelius Gabriel Omlin ◽  
...  
Keyword(s):  
Decision Making ◽  
Clinical Practice ◽  
Bone Scan ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Response To Treatment ◽  
Clinical Progression ◽  
Online Questionnaire ◽  
Main Challenge ◽  
Access To Technology

296 Background: Increased availability of treatment options in CRPC requires improved biomarkers to optimize decision making for therapeutic sequencing. Despite evidence for the value of CTCs in assessing prognosis and response to treatment, their use in clinical practice is not widely implemented. Clinicians rely on PCWG2 criteria based on PSA, clinical and radiological criteria although these are only inconsistently used in clinical practice. We evaluated the trends for clinical decision-making by physicians treating CRPC. Methods: An online questionnaire was distributed to physicians treating PC from the UK, Switzerland and Australia. Questions on clinical practice, familiarity with progression criteria, use of CTCs and clinical-decision making were formulated. Results: 111 participants replied. Most (84.7%) were oncologists treating ≥ 50 patients per year (65.3%). Although only 39.6% usually used PCWG2 in clinical practice, 74.5% considered PSA, bone scans and CT to be useful for monitoring disease. 55.6% considered PSA to be an important biomarker. A minority were able to identify PSA (41.4%) and bone scan (39.4%) progression criteria by PCWG2. On average, more physicians discontinued cabazitaxel (28%) than docetaxel (10.4%) before cycle 4. Similar number of cycles were given to bone only disease compared to RECIST evaluable patients. Clinical progression was most important for switching treatment for most physicians (90.5%), followed by RECIST (71.6%), bone scan (47.7%), CTC (23.2%) and PSA (21.1%). The main challenge associated with the use of CTCs was the access to technology (84.7%). Most respondents (92%) would not stop therapy with rising PSA but falling CTC counts; most (88.8%) would not stop with declining PSA but rising CTCs. Although 50% acknowledged the prognostic value of CTCs, only 33% would use them to guide decision-making. Conclusions: A significant number of physicians discontinue treatment before 12 weeks. Most physicians rely on clinical progression for decision-making. Knowledge of PCWG2 response and progression criteria is generally suboptimal. Greater physician awareness, access to technology and further evidence and will be required for the implementation of CTCs as a routine biomarker in CRPC.

scholarly journals Mechanisms and Clinical Applications of Genome Instability in Multiple Myeloma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Antonia Cagnetta ◽  
Davide Lovera ◽  
Raffaella Grasso ◽  
Nicoletta Colombo ◽  
Letizia Canepa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Genomic Instability ◽  
Molecular Basis ◽  
Genome Instability ◽  
Dna Recombination ◽  
Clinical Applications ◽  
Response To Treatment ◽  
Chromosomal Segregation ◽  
Telomere Function ◽  
Mitotic Regulation

Ongoing genomic instability represents a hallmark of multiple myeloma (MM) cells, which manifests largely as whole chromosome- or translocation-based aneuploidy. Importantly, although it supports tumorigenesis, progression and, response to treatment in MM patients, it remains one of the least understood components of malignant transformation in terms of molecular basis. Therefore these aspects make the comprehension of genomic instability a pioneering strategy for novel therapeutic and clinical speculations to use in the management of MM patients. Here we will review mechanisms mediating genomic instability in MM cells with an emphasis placed on pathogenic mutations affecting DNA recombination, replication and repair, telomere function and mitotic regulation of spindle attachment, centrosome function, and chromosomal segregation. We will discuss the mechanisms by which genetic aberrations give rise to multiple pathogenic events required for myelomagenesis and conclude with a discussion of the clinical applications of these findings in MM patients.

scholarly journals SGPNet: A Three-Dimensional Multitask Residual Framework for Segmentation and IDH Genotype Prediction of Gliomas

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yao Wang ◽  
Yan Wang ◽  
Chunjie Guo ◽  
Shuangquan Zhang ◽  
Lili Yang
Keyword(s):  
Brain Tumor ◽  
Clinical Decision Making ◽  
Three Dimensional ◽  
Clinical Decision ◽  
Error Rates ◽  
The Cancer Genome Atlas ◽  
Classification Error ◽  
Tumor Segmentation ◽  
Brain Tumor Segmentation ◽  
The Status

Glioma is the main type of malignant brain tumor in adults, and the status of isocitrate dehydrogenase (IDH) mutation highly affects the diagnosis, treatment, and prognosis of gliomas. Radiographic medical imaging provides a noninvasive platform for sampling both inter and intralesion heterogeneity of gliomas, and previous research has shown that the IDH genotype can be predicted from the fusion of multimodality radiology images. The features of medical images and IDH genotype are vital for medical treatment; however, it still lacks a multitask framework for the segmentation of the lesion areas of gliomas and the prediction of IDH genotype. In this paper, we propose a novel three-dimensional (3D) multitask deep learning model for segmentation and genotype prediction (SGPNet). The residual units are also introduced into the SGPNet that allows the output blocks to extract hierarchical features for different tasks and facilitate the information propagation. Our model reduces 26.6% classification error rates comparing with previous models on the datasets of Multimodal Brain Tumor Segmentation Challenge (BRATS) 2020 and The Cancer Genome Atlas (TCGA) gliomas’ databases. Furthermore, we first practically investigate the influence of lesion areas on the performance of IDH genotype prediction by setting different groups of learning targets. The experimental results indicate that the information of lesion areas is more important for the IDH genotype prediction. Our framework is effective and generalizable, which can serve as a highly automated tool to be applied in clinical decision making.

scholarly journals Investigating the Benefits of Using 3D Camera Technology to Improve Wound Measurements in a Tissue Viability Service: Outcomes of a Pilot Implementation Study

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
King BM ◽  
◽  
Doyle K ◽  
Kelley J ◽  
Taylor C ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Outcome Measurement ◽  
Three Dimensional ◽  
Clinical Decision ◽  
Case Depth ◽  
Continuous Assessment ◽  
Tissue Viability ◽  
Important Indicator ◽  
Manual Measurement ◽  
Depth Measurement

Sub-optimal experience and outcomes for people with stalled wounds is common. Clinicians have limited methods for reliably and accurately measure wounds. Depth measurement is an important indicator of healing, and digital methods of imaging the wound may offer increased accuracy and enable clinical decision-making. This study aimed to implement a Panasonic FZ-M1 toughpad with WoundCareLite software version 1.5.0.0, to enable three-dimensional measurements in Tissue Viability (TV) service. Length, width, and depth measurement were compared with usual manual measurement using a paper ruler alongside a 2D photographic image. Statistical analysis included the comparison of wound dimension measures and a presentation of visual healing trajectories over 4 weeks using run-charts. 30 patients were recruited over five weeks (13 female and 17 male), representing 4% of the usual caseload. Manual measurement and 3D software automatic method demonstrated that the width and depth 3D auto measures were more accurate than manual measures but depth measures were often wrong thus making volumetric measures inaccurate. Consistent wound size measurement was feasible, and healing trajectories provide a useful means of continuous assessment. Technology guided measurement has potential benefits over manual measurement as a means of more accurately monitoring healing. In this case, depth measurement could not be accurately assessed in practice and further software innovation is indicated to enable outcome measurement in tissue viability services.

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