Development of a model care pathway for adults undergoing colorectal cancer surgery: Evidence-based key interventions and indicators

During the last decades, perioperative care for patients with colorectal cancer has shifted towards more standardized care, so-called "enhanced recovery after surgery." Those programs aim to optimize interventions in perioperative care to decrease the rate of postoperative complications, improve patients' recovery, and shorten hospital stay. The purpose of this literature review is to identify, summarize, and operationalize the clinical content of both key interventions and clinical indicators to develop an evidence-based model pathway for surgical patients with colorectal cancer.status: publishe

Development of a model care pathway for adults undergoing colorectal cancer surgery: Evidence-based key interventions and indicators

RATIONALE, AIMS, AND OBJECTIVES: During the last decades, perioperative care for patients with colorectal cancer has shifted towards more standardized care, so-called "enhanced recovery after surgery." Those programs aim to optimize interventions in perioperative care to decrease the rate of postoperative complications, improve patients' recovery, and shorten hospital stay. The purpose of this literature review is to identify, summarize, and operationalize the clinical content of both key interventions and clinical indicators to develop an evidence-based model pathway for surgical patients with colorectal cancer. METHODS: A systematic search in 3 databases was conducted to identify key interventions (KIs) and indicators to measure the effect of implementation of care pathways. The KIs from the enhanced recovery after surgery protocol were listed and used as framework to identify and match KIs used in the included studies. The Clinical Pathway Compass was used to categorize the indicators. RESULTS: Fifteen studies were included. The number of KI used in the study protocols ranged from 9 to 20. In total, 33 KIs were identified. Little information was available concerning the implementation of and compliance to the protocol. Length of stay and complication rate are the most common used indicators (used in 15/15 and 14/15 of the studies), followed by 21 other measures. All but one of the included studies reported a reduction in length of stay. CONCLUSION: There is a considerable variation in both number of KIs and indicators as well as operationalization of key interventions, for surgical patients with colorectal cancer documented in literature. Therefore, we summarized the input from different studies and developed an evidence-based model pathway, which can serve as a basis for a local/regional care pathway team to build their own pathway.tal cancer

B-cell replication history and somatic hypermutation status identify distinct pathophysiologic backgrounds in common variable immunodeficiency.

Item does not contain fulltextCommon variable immunodeficiency disorder (CVID) is the most prevalent form of primary idiopathic hypogammaglobulinemia. Identification of genetic defects in CVID is hampered by clinical and immunologic heterogeneity. By flow cytometric immunophenotyping and cell sorting of peripheral B-cell subsets of 37 CVID patients, we studied the B-cell compartment at the B-cell subset level using the kappa-deleting recombination excision circle assay to determine the replication history and the Igkappa-restriction enzyme hot-spot mutation assay to assess the somatic hypermutation status. Using this approach, 5 B-cell patterns were identified, which delineated groups with unique replication and somatic hypermutation characteristics. Each B-cell pattern reflected an immunologically homogenous patient group for which we proposed a different pathophysiology: (1) a B-cell production defect (n = 8, 18%), (2) an early peripheral B-cell maturation or survival defect (n = 4, 11%), (3) a B-cell activation and proliferation defect (n = 12, 32%), (4) a germinal center defect (n = 7, 19%), and (5) a postgerminal center defect (n = 6, 16%). The results of the present study provide for the first time insight into the underlying pathophysiologic background in 5 immunologically homogenous groups of CVID patients. Moreover, this study forms the basis for larger cohort studies with the defined homogenous patient groups and will facilitate the identification of underlying genetic defects in CVID

XLF deficiency results in reduced N-nucleotide addition during V(D)J recombination

Repair of DNA double-strand breaks (DSBs) by the nonhomologous end-joining pathway (NHEJ) is important not only for repair of spontaneous breaks but also for breaks induced in developing lymphocytes during V(D)J (variable [V], diversity [D], and joining [J] genes) recombination of their antigen receptor loci to create a diverse repertoire. Mutations in the NHEJ factor XLF result in extreme sensitivity for ionizing radiation, microcephaly, and growth retardation comparable to mutations in LIG4 and XRCC4, which together form the NHEJ ligation complex. However, the effect on the immune system is variable (mild to severe immunodeficiency) and less prominent than that seen in deficiencies of NHEJ factors ARTEMIS and DNA-dependent protein kinase catalytic subunit, with defects in the hairpin opening step, which is crucial and unique for V(D)J recombination. Therefore, we aimed to study the role of XLF during V(D)J recombination. We obtained clinical data from 9 XLF-deficient patients and performed immune phenotyping and antigen receptor repertoire analysis of immunoglobulin (Ig) and T-cell receptor (TR) rearrangements, using next-generation sequencing in 6 patients. The results were compared with XRCC4 and LIG4 deficiency. Both Ig and TR rearrangements showed a significant decrease in the number of nontemplated (N) nucleotides inserted by terminal deoxynucleotidyl transferase, which resulted in a decrease of 2 to 3 amino acids in the CDR3. Such a reduction in the number of N-nucleotides has a great effect on the junctional diversity, and thereby on the total diversity of the Ig and TR repertoire. This shows that XLF has an important role during V(D)J recombination in creating diversity of the repertoire by stimulating N-nucleotide insertion

Immunodeficiency in Bloom's Syndrome

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