PRACTICE guidelines are systematically developed recommendationsThis document updates the Practice Guidelines for the Prevention, that assist the practitioner and patient in making decisions about ...healthDetection and Management of Respiratory Depression Associated with care. These recommendations may be adopted, modified, or rejectedNeuraxial Opioid Administration adopted by ASA in 2007, and includes according to clinical needs and constraints, and are not intended tonew survey data and recommendations pertaining to monitoring for replace local institutional policies. In addition, practice guidelinesrespiratory depression. developed by the American Society of Anesthesiologists (ASA) are not intended as standards or absolute requirements, and their use cannot guarantee any specific outcome. Practice guidelines are subject to revision as warranted by the evolution of medical knowledge, technology, and practice. They provide basic recommendations that are supported by a synthesis and analysis of the current literature, expert and practitioner opinion, open forum commentary, and clinical feasibility data.
Single-cell transcriptome analysis overcomes problems inherently associated with averaging gene expression measurements in bulk analysis. However, single-cell analysis is currently challenging in ...terms of cost, throughput and robustness. Here, we present a method enabling massive microarray-based barcoding of expression patterns in single cells, termed MASC-seq. This technology enables both imaging and high-throughput single-cell analysis, characterizing thousands of single-cell transcriptomes per day at a low cost (0.13 USD/cell), which is two orders of magnitude less than commercially available systems. Our novel approach provides data in a rapid and simple way. Therefore, MASC-seq has the potential to accelerate the study of subtle clonal dynamics and help provide critical insights into disease development and other biological processes.
As guidelines proliferate and are used to inform efforts to improve the quality and efficiency of care, disputes over guideline recommendations are likely to become more common and contentious. It is ...appropriate for guidelines to come under close scrutiny, given their important clinical and policy implications, and critiques that point out missing evidence, improper methods, or errors in interpretation can be valuable. But for critiques to be valid, they should be based on accurate information and a sound scientific basis. A 2009 guideline sponsored by the American Pain Society (APS) on the use of invasive tests and interventional procedures found insufficient evidence to make recommendations for most interventional procedures. It was subsequently the subject of lengthy critiques by the American Society of Interventional Pain Physicians (ASIPP) that sought to challenge the methods used to develop the APS guideline, point out alleged errors in the evidence review commissioned to inform the guideline, and question the integrity of the APS guideline process. We show that the ASIPP critiques contain numerous errors and fail to adhere to scientific standards for reviewing evidence, and provide suggestions on how future disputes regarding guidelines might be addressed in a more constructive manner.
In order to best serve patients and clinicians, debates over guidelines should be based on accurate information, adhere to current methodological standards, acknowledge important deficiencies in the evidence when they are present, and handle conflicts of interest in a vigorous and transparent manner.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chronic lymphocytic leukemia (CLL) is a clinically and biologically heterogeneous disease with varying outcomes. In the last decade, the application of next-generation sequencing technologies has ...allowed extensive mapping of disease-specific genomic, epigenomic, immunogenetic, and transcriptomic signatures linked to CLL pathogenesis. These technologies have improved our understanding of the impact of tumor heterogeneity and evolution on disease outcome, although they have mostly been performed on bulk preparations of nucleic acids. As a further development, new technologies have emerged in recent years that allow high-resolution mapping at the single-cell level. These include single-cell RNA sequencing for assessment of the transcriptome, both of leukemic and non-malignant cells in the tumor microenvironment; immunogenetic profiling of B and T cell receptor rearrangements; single-cell sequencing methods for investigation of methylation and chromatin accessibility across the genome; and targeted single-cell DNA sequencing for analysis of copy-number alterations and single nucleotide variants. In addition, concomitant profiling of cellular subpopulations, based on protein expression, can also be obtained by various antibody-based approaches. In this review, we discuss different single-cell sequencing technologies and how they have been applied so far to study CLL onset and progression, also in response to treatment. This latter aspect is particularly relevant considering that we are moving away from chemoimmunotherapy to targeted therapies, with a potentially distinct impact on clonal dynamics. We also discuss new possibilities, such as integrative multi-omics analysis, as well as inherent limitations of the different single-cell technologies, from sample preparation to data interpretation using available bioinformatic pipelines. Finally, we discuss future directions in this rapidly evolving field.
DNA repair mechanisms are fundamental for B cell development, which relies on the somatic diversification of the immunoglobulin genes by V(D)J recombination, somatic hypermutation, and class switch ...recombination. Their failure is postulated to promote genomic instability and malignant transformation in B cells. By performing targeted sequencing of 73 key DNA repair genes in 29 B cell lymphoma samples, somatic and germline mutations were identified in various DNA repair pathways, mainly in diffuse large B cell lymphomas (DLBCLs). Mutations in mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite instability, increased number of somatic insertions/deletions, and altered mutation signatures in tumors. Somatic mutations in nonhomologous end-joining (NHEJ) genes (DCLRE1C/ARTEMIS, PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were identified in four DLBCL tumors and cytogenetic analyses revealed that translocations involving the immunoglobulin-heavy chain locus occurred exclusively in NHEJ-mutated samples. The novel mutation targets, CHEK2 and PARP1, were further screened in expanded DLBCL cohorts, and somatic as well as novel and rare germline mutations were identified in 8 and 5% of analyzed tumors, respectively. By correlating defects in a subset of DNA damage response and repair genes with genomic instability events in tumors, we propose that these genes play a role in DLBCL lymphomagenesis.
Medulloblastoma is a malignant embryonal tumor of the central nervous system (CNS) that mainly affects infants and children. Prognosis is highly variable, and molecular biomarkers for measurable ...residual disease (MRD) detection are lacking. Analysis of cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) using broad genomic approaches, such as low-coverage whole-genome sequencing, has shown promising prognostic value. However, more sensitive methods are needed for MRD analysis. Here, we show the technical feasibility of capturing medulloblastoma-associated structural variants and point mutations simultaneously in cfDNA using multiplexed droplet digital PCR (ddPCR). Assay sensitivity was assessed with a dilution series of tumor in normal genomic DNA, and the limit of detection was below 100 pg of input DNA for all assays. False positive rates were zero for structural variant assays. Liquid biopsies (CSF and plasma, n = 47) were analyzed from 12 children with medulloblastoma, all with negative CSF cytology. MRD was detected in 75% (9/12) of patients overall. In CSF samples taken before or within 21 days of surgery, MRD was detected in 88% (7/8) of patients with localized disease and in one patient with the metastasized disease. Our results suggest that this approach could expand the utility of ddPCR and complement broader analyses of cfDNA for MRD detection.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Lumbar spinal stenosis (LSS) can lead to compression of neural elements and manifest as low back and leg pain. LSS has traditionally been treated with a variety of conservative (pain ...medications, physical therapy, epidural spinal injections) and invasive (surgical decompression) options. Recently, several minimally invasive procedures have expanded the treatment options.
Methods
The Lumbar Spinal Stenosis Consensus Group convened to evaluate the peer‐reviewed literature as the basis for making minimally invasive spine treatment (MIST) recommendations. Eleven consensus points were clearly defined with evidence strength, recommendation grade, and consensus level using U.S. Preventive Services Task Force criteria. The Consensus Group also created a treatment algorithm. Literature searches yielded 9 studies (2 randomized controlled trials RCTs; 7 observational studies, 4 prospective and 3 retrospective) of minimally invasive spine treatments, and 1 RCT for spacers.
Results
The LSS treatment choice is dependent on the degree of stenosis; spinal or anatomic level; architecture of the stenosis; severity of the symptoms; failed, past, less invasive treatments; previous fusions or other open surgical approaches; and patient comorbidities. There is Level I evidence for percutaneous image‐guided lumbar decompression as superior to lumbar epidural steroid injection, and 1 RCT supported spacer use in a noninferiority study comparing 2 spacer products currently available.
Conclusions
MISTs should be used in a judicious and algorithmic fashion to treat LSS, based on the evidence of efficacy and safety in the peer‐reviewed literature. The MIST Consensus Group recommend that these procedures be used in a multimodal fashion as part of an evidence‐based decision algorithm.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML). ...We have performed a thorough prognostic evaluation of these genetic markers in patients with pediatric AML enrolled in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients, respectively. Presence of FLT3-internal tandem duplication (ITD) was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of patients with pediatric AML and that determination of the BAALC gene expression level can add valuable information.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chronic pain impacts more than 100 million Americans and has a significant impact on the economy and quality of life. Spinal cord stimulation (SCS) has demonstrated efficacy in managing a growing ...number of chronic pain conditions. This in combination with an increasing number of physicians trained in SCS placement has produced significant changes in utilization, expense and sites of service related to SCS. In particular, there has been a large increase in SCS placement by non-surgeons, use of percutaneous leads and performance in ambulatory surgery centers instead of inpatient settings. There are also notable differences in SCS use related to age, race, insurance coverage and geography. There is a large potential market and use of these therapies is predicted to grow from $2.41 billion in 2020 to $4.12 billion US dollars globally by 2027. At the same time, there is increasing scrutiny around utilization of this therapy related to cost, complications, long-term efficacy and explant rates that has the potential to impact access to this therapy in the future. We must examine our indications, technique and management to optimize outcomes and utilization of SCS going forward.
PDF
