Implementation of a quadratus lumborum regional block protocol with assessment of effectiveness for patients with appendicitis: a quality improvement project.

PURPOSE: This study analyzes the implementation of the routine use of quadratus lumborum blocks (QLBs) on postoperative pain and opioid consumption among children undergoing laparoscopic appendectomy compared to those not receiving regional anesthesia. METHODS: Children undergoing laparoscopic appendectomy within a multi-hospital children's healthcare system were retrospectively reviewed from 2017 to 2021. Patients were stratified by appendicitis type (uncomplicated vs. complicated). Pain scores and opioid consumption in the post-anesthesia care unit (PACU) and within the first 24 h postoperatively were compared by block status (no block [NB] vs. QLB) and appendicitis type. RESULTS: 2033 patients were reviewed, and 610 received a QLB. The frequency of rescue opioid use was reduced in the PACU (uncomplicated: QLB 46.6% vs. NB 54.6%, p = 0.005; complicated: QLB 28.5% vs. NB 39.9%, p = 0.01) and postoperatively (complicated: QLB 33.7% vs. NB 52.9%, p < 0.001) for those who received a QLB. This resulted in reduced opioid consumption as measured by morphine milligram equivalents per kilogram postoperatively. CONCLUSION: QLBs can be safely administered in children and provide improvements in opioid consumption postoperatively. QLBs should remain a strongly favored regional anesthetic technique because of their wide applicability for abdominal surgeries to minimize rescue opioid analgesic use. TYPE OF STUDY: Retrospective comparative study. LEVEL OF EVIDENCE: Level III.

Patient-Reported Outcomes in Pain Management After Ambulatory Pediatric General and Urologic Surgery.

BACKGROUND: Many studies evaluating opioid stewardship interventions' effects on postoperative pain rely on emergency department (ED) visits or readmissions, but patient-reported pain scores represent a more complete picture of the postoperative experience. This study compares patient-reported pain scores after ambulatory pediatric and urologic procedures and the effect of an opioid stewardship intervention that nearly eliminated the use of outpatient narcotics. METHODS: This is a retrospective comparative study including 3173 pediatric patients who underwent ambulatory procedures from 2015 to 2019, during which there was an intervention to reduce narcotic prescriptions. Postoperative day one phone calls assessed pain levels using a four-point scale (no pain, mild pain, moderate pain controlled with medication, or severe pain uncontrolled with medication). We quantified the proportion of patients prescribed opioids pre-versus post-intervention and compared pain scores for patients receiving opioid versus non-opioid regimens. RESULTS: Opioid prescription rates demonstrated a 6.5-fold reduction after opioid stewardship efforts. The majority of patients (2838) received non-opioids, with only 335 patients receiving opioids. Opioid patients reported moderate/severe pain slightly more than non-opioid patients (14.1% vs. 10.4%, p = 0.04). On by-procedure analyses, there were no subgroups in which non-opioid patients reported significantly higher pain scores. CONCLUSIONS: Non-opioid postoperative pain regimens appear to be effective, with only 10.4% of patients reporting moderate/severe pain after ambulatory procedures. Future studies assessing patient-reported outcomes are necessary to optimize pain control for all patients and to determine whether there is ever an indication for opioid prescription after ambulatory general pediatric or urologic surgery. TYPE OF STUDY: Retrospective comparative study. LEVEL OF EVIDENCE: Level III.

Evaluating comfort measures for commonly performed painful procedures in pediatric patients.

INTRODUCTION: Management of pediatric pain from medical procedures is of great importance for improving both patient care and experience. In this study, we investigated methods of managing acute pain in infants and children by studying the correlation between the number of attempts to complete painful procedures, given different comfort measures. METHODS: The study is a retrospective review of 74,276 procedures performed at two pediatric hospitals in an integrated academic children's health system between 2013 and 2016. We compared three comfort measures most frequently offered: positions of comfort (POC), distraction (DIST), and pharmacological (PHARM). These methods were compared in the setting of four procedures: peripheral intravenous (PIV) catheter insertion, gastrointestinal tube placement, incision procedures, and bladder catheterization. We used the number of attempts needed to complete a procedure as a measure of efficacy minimizing distressing experience in an acutely painful setting (single attempt vs repeat attempts). RESULTS: Among younger children, DIST appears superior to the other two methods; it performs significantly better for three of the four procedures (PIV catheterization, incision wound, and urinary catheterization) among infants aged <1 year and for PIV catheterization among toddlers aged 1-3 years. For older children, POC tends to perform slightly better than the other two methods, although it is significantly better only for PIV catheterization among adolescents aged 13-21 years and urinary catheterization among children aged 9-12 years. CONCLUSION: Results from this study may be used to determine appropriate comfort measures for painful procedures in pediatric setting.

Evidence for a macromolecular complex in poor prognosis CLL that contains CD38, CD49d, CD44 and MMP-9.

Progressive chronic lymphocytic leukaemia is characterized by the accumulation of neoplastic B-cells in the tissues and correlates with the expression of prognostic biomarkers, such as CD38, CD49d and matrix metalloproteinase-9 (MMP9), which are involved in migration and tissue invasion. In this study we investigated the physical relationship between these molecules and demonstrated that CD38, CD49d, MMP9 and CD44 were physically associated in a supramolecular cell surface complex. Our findings provide a molecular basis for the correlation between expression of these proteins and prognosis and, as the complex is not present in normal B-cells, suggest a novel leukaemia-specific therapeutic target.

CD49d is an independent prognostic marker that is associated with CXCR4 expression in CLL.

The world of chronic lymphocytic leukemia (CLL) research is awash with prognostic markers. However, very few of the current group play a clearly defined role in the pathology of this disease and even fewer represent a tractable therapeutic target. One such marker that fulfils both of these criteria is the integrin CD49d. This molecule been implicated in the capacity of CLL cells to migrate into lymphoid tissues and there is a CD49d blocking antibody, Natalizumab, currently in clinical trials. Here we carried out the largest multi-centre evaluation of CD49d as a prognostic marker in 652 primary CLL samples. We confirm that CD49d is predictive for time to first treatment (P<0.0001) and overall survival (P<0.0001) and increases the prognostic power of CD38, ZAP-70 and IGHV gene mutation status in concordant cases. Furthermore, CD49d retained independent prognostic significance in multivariate analysis. In contrast to previous studies, we showed no correlation between CD49d expression and in vitro resistance to fludarabine in liquid cultures (P=0.28) but CD49d(hi) cells were significantly more resistant than CD49d(lo) cells when assays were carried out on fibronectin-coated plates (P=0.03). Furthermore, we showed for the first time that the expression of CD49d is strongly associated with expression of the chemokine receptor CXCR4 suggesting a co-ordinated role for these molecules in the trafficking of CLL cells to the lymphoid tissues. Taken together, our data support the introduction of CD49d into routine immunophenotyping panels for CLL and indicate that the therapeutic targeting of this molecule may prove useful in this disease.

Peripheral blood but not tissue dendritic cells express CD52 and are depleted by treatment with alemtuzumab.

CAMPATH antibodies recognize CD52, a phosphatidylinositol-linked membrane protein expressed by mature lymphocytes and monocytes. Since some antigen-presenting dendritic cells (DCs) differentiate from a monocytic progenitor, we investigated the expression of CD52 on dendritic cell subsets. Four-color staining for lineage markers (CD3, 14, 16, 19, 20, 34, and 56), HLA-DR, CD52, and CD123 or CD11c demonstrated that myeloid peripheral blood (PB) DCs, defined as lineage(-)HLA-DR(+)CD11c(+), express CD52, while expression by CD123(+) lymphoid DCs was variable. Depletion of CD52(+) cells from normal PB strongly inhibited their stimulatory activity in an allogeneic mixed lymphocyte reaction and also reduced the primary autologous response to the potent neoantigen keyhole limpet hemocyanin. CD52 is thus expressed by a myeloid subset of PBDCs that is strongly allostimulatory and capable of initiating a primary immune response to soluble antigen. Administration of alemtuzumab, a humanized monoclonal antibody against CD52, to patients with lymphoproliferative disorders or as conditioning for hematopoietic stem cell transplantation resulted in a marked reduction in circulating lineage(-)HLA-DR(+) DCs (mean 31-fold reduction, P =.043). Analysis of monocyte-derived DCs in vitro revealed a reduction in CD52 expression during culture in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4, with complete loss following activation-induced maturation with lipopolysaccharide. In contrast to the findings in PB, epidermal and small-intestine DCs did not express CD52, suggesting either that transit from blood to epidermis and gut is associated with loss of CD52 or that DCs in these tissues originate from another population of cells.