Antibody-Suppressor CXCR5+CD8+ T Cells Are More Potent Regulators of Humoral Alloimmunity after Kidney Transplant in Mice Compared to CD4+ Regulatory T Cells.

Adoptive cell therapy (ACT), especially with CD4+ regulatory T cells (CD4+ Tregs), is an emerging therapeutic strategy to minimize immunosuppression and promote long-term allograft acceptance, although much research remains to realize its potential. In this study, we investigated the potency of novel Ab-suppressor CXCR5+CD8+ T cells (CD8+ TAb-supp) in comparison with conventional CD25highFoxp3+CD4+ Tregs for suppression of humoral alloimmunity in a murine kidney transplant (KTx) model of Ab-mediated rejection (AMR). We examined quantity of peripheral blood, splenic and graft-infiltrating CD8+ TAb-supp, and CD4+ Tregs in KTx recipients and found that high alloantibody-producing CCR5 knockout KTx recipients have significantly fewer post-transplant peripheral blood and splenic CD8+ TAb-supp, as well as fewer splenic and graft-infiltrating CD4+ Tregs compared with wild-type KTx recipients. ACT with alloprimed CXCR5+CD8+ T cells reduced alloantibody titer, splenic alloprimed germinal center (GC) B cell quantity, and improved AMR histology in CCR5 knockout KTx recipients. ACT with alloprimed CD4+ Treg cells improved AMR histology without significantly inhibiting alloantibody production or the quantity of splenic alloprimed GC B cells. Studies with TCR transgenic mice confirmed Ag specificity of CD8+ TAb-supp-mediated effector function. In wild-type recipients, CD8 depletion significantly increased alloantibody titer, GC B cells, and severity of AMR pathology compared with isotype-treated controls. Anti-CD25 mAb treatment also resulted in increased but less pronounced effect on alloantibody titer, quantity of GC B cells, and AMR pathology than CD8 depletion. To our knowledge, this is the first report that CD8+ TAb-supp cells are more potent regulators of humoral alloimmunity than CD4+ Treg cells.

Clinical impacts of immunomodulator withdrawal from anti-tumor necrosis factor combination therapy in pediatric inflammatory bowel disease.

OBJECTIVES: Combination therapy consists of both anti-tumor necrosis factor (anti-TNF) and an immunomodulator (IMM) and has been shown to improve outcomes in patients with inflammatory bowel disease (IBD). This study assesses the impacts of IMM withdrawal from combination therapy to anti-TNF monotherapy in children with IBD. METHODS: This single-center retrospective cohort study included children with IBD initiated on combination therapy between 2014 and 2019 who discontinued the IMM. We evaluated whether IMM withdrawal impacts laboratory values and disease activity. Linear mixed effects models with random intercepts were used to compare differences between groups. Chi-square and Kruskal-Wallis tests were used for comparisons between patients who did and did not require subsequent escalation of therapy. RESULTS: One hundred and fifty-two patients discontinued the IMM which did not significantly affect disease activity. However, 18% of patients escalated therapy after IMM withdrawal, primarily due to low anti-TNF levels. Lower anti-TNF and higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels before IMM withdrawal were associated with subsequent escalation of therapy. Overall, there was no statistically significant effect on anti-TNF drug levels. Patients with Crohn's disease (CD) on infliximab (IFX) and methotrexate (MTX) who discontinued the IMM had an increase in mean ESR and CRP (p < 0.05). CONCLUSIONS: IMM withdrawal from anti-TNF combination therapy may be considered safe in the setting of higher anti-TNF levels and normal serum inflammatory markers. Clinicians should consider assessing anti-TNF levels and inflammatory markers after IMM withdrawal, especially in patients with CD receiving IFX who discontinued MTX.

Clinical outcomes and cost savings of a nonmedical switch to a biosimilar in children/young adults with inflammatory bowel disease.

OBJECTIVES: The safety, efficacy, and cost savings associated with biosimilar medications are well established. However, a lack of pediatric data exists surrounding clinical outcomes when switching from an originator to a biosimilar. Our primary aim is to evaluate clinical outcomes following a nonmedical switch from the infliximab originator to a biosimilar in children and young adults with inflammatory bowel disease (IBD). Our secondary aim is to estimate cost savings associated with this switch. METHODS: A quality improvement project was implemented to establish safe switching protocols, then those patients who underwent a nonmedical switch from the infliximab originator to the biosimilar were retrospectively reviewed. Demographic data, physician global assessments (PGAs), and laboratory values were recorded 1 year pre- and post-switch. Continuation rates on the biosimilar were reported at 6 and 12 months. Cost savings were estimated using two different pricing models. RESULTS: Fifty-three patients underwent a nonmedical switch. Laboratory values including inflammatory markers, infliximab levels, and PGA scores remained similar when assessed pre- and post-switch. No infusion reactions or antidrug antibody development occurred. Two patients reported psoriasis-like rashes. Five patients switched back to the originator during the study period. There were 379 biosimilar infusions completed with an estimated total cost savings of $11,260 (average sales price) and $566,223 (wholesale acquisition cost). CONCLUSIONS: Clinical remission rates, inflammatory laboratory markers, serious adverse events, infliximab levels, and antidrug antibodies remained similar after a one-time nonmedical switch to an infliximab biosimilar. Nonmedical switching to biosimilars resulted in significant cost savings.

Patient-perceived understanding of home-going medication with transitions of care services at a pediatric institution.

BACKGROUND: Transitions of care (TOC) is the coordination and continuity of health care as a patient transfers between different settings. This can include a wide range of services, such as medication reconciliation, patient counseling, bedside delivery of medications, and others that meet individual patient needs. In the pediatric population, patients are at increased risk of potential medication errors and subsequent harm owing to reduced patient and caregiver health literacy, limited dosage form availability, and errors in medication administration. The use of TOC services at the time of hospital discharge in this population has the potential to make a positive impact on patient safety and the treatment of medical conditions. OBJECTIVES: The primary objective of this study was to determine whether patient-perceived understanding of home-going medications was greater in patients and/or caregivers who received medication bedside delivery and education from a pharmacy-led TOC service at a large pediatric academic medical center. The secondary objective was to determine whether the primary practice area of the pharmacist providing medication education led to changes in understanding of home-going medication(s). METHODS: Using institution-wide, patient satisfaction surveys from January 1, 2021, to December 31, 2021, patient and caregiver responses were queried for 2 questions about home-going medications, relating to the understanding of administration and the potential adverse effects. Patients were divided into 2 groups depending on TOC services received, as documented in the electronic medical record (EMR). Survey responses for each of the 2 questions were categorized as top-box percentage by study group. Hypothesis testing between study groups for the primary and secondary outcomes were conducted using chi-squared tests at an alpha of 0.05. Statistical analyses were conducted using SAS version 9.4. RESULTS: Of the 1159 patients included in the study, 441 received TOC services, deemed the intervention group, and 718 did not receive TOC services, deemed the control group. When the intervention and control group were asked about understanding of medication administration, 96.37% versus 93.18% of patients (P = 0.007) gave the most favorable response of "yes, definitely," respectively. Furthermore, 78.51% versus 77.44% of patients (P = 0.053) gave the most favorable response when asked about understanding potential medication adverse effects, respectively. CONCLUSION: Patients receiving TOC services by a member of the pharmacy team had a greater score for understanding of both medication administration and adverse effects. Furthermore, this greater score was consistent among the education provided by the inpatient and outpatient pharmacist.

Discrepancy Between Reported and Calculated Pain Reduction in Patients With Spinal Cord Stimulation Therapy and Lack of Agreement Between Patient Satisfaction and Degree of Pain Relief.

OBJECTIVES: This study aimed to determine agreement between reported percentage pain reduction (RPPR) and calculated percentage pain reduction (CPPR) in patients with percutaneous spinal cord stimulation (SCS) implants, and to correlate RPPR and CPPR with patient satisfaction. We also sought to determine which patient-reported outcome measures are most improved in patients with SCS. MATERIALS AND METHODS: Fifty patients with percutaneous spinal cord stimulator implants with a mean follow-up of 51.1 months were interviewed and surveyed to assess their pain level, impression of degree of pain relief, satisfaction with the therapy, and desire to have the device again. Baseline pain level was obtained from their preimplant records. RESULTS: Overall, RPPR was found to be 53.3%, whereas CPPR was 44.4%. Of all patients, 21 reported <50% pain reduction; however, most of these (12/21, 57%) were satisfied with the outcome of therapy. In terms of individual improvement in outcomes, activities of daily life was the most improved measure at 82%, followed by mood, sleep, medication use, and health care utilization at 74%, 62%, 50%, and 48%, respectively. CONCLUSIONS: RPPR appears to be a complex outcome measure that may not agree with CPPR. Overall RPPR is greater than the CPPR. On the basis of our data, these independently valid measures should not be used interchangeably. A 50% pain reduction threshold is not a requisite for patient satisfaction and desire to have the device again. Activities of daily living was the most improved measure in this cohort, followed by mood, sleep, medication usage, and decrease in health care utilization.

Incidence of subsequent surgical decompression following minimally invasive approaches to treat lumbar spinal stenosis: A retrospective review.

BACKGROUND CONTEXT: Surgical decompression is the definitive treatment for managing symptomatic lumbar spinal stenosis; however, select patients are poor surgical candidates. Consequently, minimally invasive procedures have gained popularity, but there exists the potential for failure of therapy necessitating eventual surgical decompression. PURPOSE: To evaluate the incidence and characteristics of patients who require surgical decompression following minimally invasive procedures to treat lumbar spinal stenosis. STUDY DESIGN/SETTING: Retrospective review. PATIENT SAMPLE: Patients who underwent minimally invasive procedures for lumbar spinal stenosis (Percutaneous Image-guided Lumbar Decompression [PILD] or interspinous spacer device [ISD]) and progressed to subsequent surgical decompression within 5 years. OUTCOME MEASURES: The primary outcome was the rate of surgical decompression within 5 years following the minimally invasive approach. Secondary outcomes included demographic and comorbid factors associated with increased odds of requiring subsequent surgery. METHODS: Patient data were collected using the PearlDiver-Mariner database. The rate of subsequent decompression was described as a percentage while univariable and multivariable regression analysis was used for the analysis of predictors. RESULTS: A total of 5278 patients were included, of which 3222 (61.04%) underwent PILD, 1959 (37.12%) underwent ISD placement, and 97 (1.84%) had claims for both procedures. Overall, the incidence of subsequent surgical decompression within 5 years was 6.56% (346 of 5278 patients). Variables associated with a significantly greater odds ratio (OR) [95% confidence interval (CI)] of requiring subsequent surgical decompression included male gender and a prior history of surgical decompression by 1.42 ([1.14, 1.77], p = 0.002) and 2.10 times ([1.39, 3.17], p < 0.001), respectively. In contrast, age 65 years and above, a diagnosis of obesity, and a Charlson Comorbidity Index score of three or greater were associated with a significantly reduced OR [95% CI] by 0.64 ([0.50, 0.81], p < 0.001), 0.62 ([0.48, 0.81], p < 0.001), and 0.71 times ([0.56, 0.91], p = 0.007), respectively. CONCLUSIONS: Minimally invasive procedures may provide an additional option to treat symptomatic lumbar spinal stenosis in patients who are poor surgical candidates or who do not desire open decompression; however, there still exists a subset of patients who will require subsequent surgical decompression. Factors such as gender and prior surgical decompression increase the likelihood of subsequent surgery, while older age, obesity, and a higher Charlson Comorbidity Index score reduce it. These findings aid in selecting suitable surgical candidates for better outcomes in the elderly population with lumbar spinal stenosis.

Mouse Model of Spinal Cord Hypoperfusion with Immediate Paralysis Caused by Endovascular Repair of Thoracic Aortic Aneurysm.

BACKGROUND: A clinically relevant mouse model of thoracic endovascular aortic repair-induced ischemic spinal cord injury has been lacking since the procedure was first employed in 1991. The hypothesis was that ligation of mouse intercostal arteries would simulate thoracic endovascular aortic repair-induced ischemic spinal cord injury and behavioral deficit. The aim was to create a mouse model of thoracic endovascular aortic repair-induced spinal cord hypoperfusion by ligating five pairs of mouse intercostal vessels. METHODS: Mice were divided into sham (n = 53) and ligation (n = 60) groups. The procedures called for double ligation of three pairs and single ligation of two pairs of thoracic intercostal arteries in adult C57BL/6 mice. A laser Doppler probe was used in vivo on the spinal cords and intercostal arteries to document the extent of arterial ligation and spinal cord hypoperfusion. The Basso Mouse Scale for Locomotion, histological studies, and electron microscopy demonstrated postligation locomotive and histopathological changes. RESULTS: Ligation induced a significant and instantaneous drop in blood flow in the intercostal arteries (% change; mean = -63.81; 95% CI, -72.28 to -55.34) and the thoracic spinal cord (% change; mean = -68.55; 95% CI, -80.23 to -56.87). Paralysis onset was immediate and of varying degree, with behavioral deficit stratified into three groups: 9.4% exhibited severe paralysis, 37.5% moderate paralysis, and 53.1% mild paralysis at day 1 (n = 32; P < 0.001). Mild and moderate paralysis was transient, gradually improving over time. Severe paralysis showed no improvement and exhibited a higher mortality rate (83%; n = 15 of 18) compared to moderately (33%; n = 6 of 18) and mildly (24%; n = 6 of 25) paralyzed mice (P < 0.001). The overall ligation group survival rate (84%; n = 46 of 55) was significantly lower than the sham group (100%; n = 48 of 48) with P = 0.003. CONCLUSIONS: The mouse model generates reproducible spinal cord hypoperfusion and accompanying histopathological ischemic spinal cord damage. The resulting anatomical changes and variable behavioral deficits mimic the variability in radiological and clinical findings in human patients.

Invariant NKT Cells Promote the Development of Highly Cytotoxic Multipotent CXCR3+CCR4+CD8+ T Cells That Mediate Rapid Hepatocyte Allograft Rejection.

Hepatocyte transplant represents a treatment for metabolic disorders but is limited by immunogenicity. Our prior work identified the critical role of CD8+ T cells, with or without CD4+ T cell help, in mediating hepatocyte rejection. In this study, we evaluated the influence of invariant NKT (iNKT) cells, uniquely abundant in the liver, upon CD8-mediated immune responses in the presence and absence of CD4+ T cells. To investigate this, C57BL/6 (wild-type) and iNKT-deficient Jα18 knockout mice (cohorts CD4 depleted) were transplanted with allogeneic hepatocytes. Recipients were evaluated for alloprimed CD8+ T cell subset composition, allocytotoxicity, and hepatocyte rejection. We found that CD8-mediated allocytotoxicity was significantly decreased in iNKT-deficient recipients and was restored by adoptive transfer of iNKT cells. In the absence of both iNKT cells and CD4+ T cells, CD8-mediated allocytotoxicity and hepatocyte rejection was abrogated. iNKT cells enhance the proportion of a novel subset of multipotent, alloprimed CXCR3+CCR4+CD8+ cytolytic T cells that develop after hepatocyte transplant and are abundant in the liver. Alloprimed CXCR3+CCR4+CD8+ T cells express cytotoxic effector molecules (perforin/granzyme and Fas ligand) and are distinguished from alloprimed CXCR3+CCR4-CD8+ T cells by a higher proportion of cells expressing TNF-α and IFN-γ. Furthermore, alloprimed CXCR3+CCR4+CD8+ T cells mediate higher allocytotoxicity and more rapid allograft rejection. Our data demonstrate the important role of iNKT cells in promoting the development of highly cytotoxic, multipotent CXCR3+CCR4+CD8+ T cells that mediate rapid rejection of allogeneic hepatocytes engrafted in the liver. Targeting iNKT cells may be an efficacious therapy to prevent rejection of intrahepatic cellular transplants.

Similar Growth Outcomes in Children with Inflammatory Bowel Disease Initiated on Infliximab Originator or Biosimilar.

BACKGROUND: Growth is an important clinical outcome, especially in childhood-onset inflammatory bowel disease (IBD). Prior research has demonstrated growth improvements with infliximab therapy. There are limited studies evaluating whether clinical and growth outcomes in children initiated on the infliximab originator and infliximab biosimilar are similar. METHODS: This was a single-center retrospective review of patients with IBD, younger than 17 years old, and initiated on the infliximab originator or biosimilar for at least 12 months between April 2016 and February 2021. Propensity score matching was utilized. Laboratory values, disease activity scores, and growth values were collected at baseline (prior to infliximab initiation), 6 months, and 12 months post initiation. Linear mixed models with random intercepts were used to test differences in measures over time and between study groups. RESULTS: There were 113 patients on the originator and 39 patients on a biosimilar who met eligibility criteria. Propensity score methodology identified 37 dyads (1:1 match). Weight, height, and body mass index z scores increased over time (from baseline to 12 months) for both groups ( P < 0.05) and there was a similar rate of change between study groups. Clinical outcomes of lab values (albumin, C-reactive protein, and hemoglobin) and disease activity scoring were similar from baseline to 12 months between study groups. CONCLUSIONS: There were similar improvements in growth and clinical outcomes in patients initiated on the infliximab originator compared to an infliximab biosimilar agent. This study adds to the limited research evaluating whether infliximab biosimilars have similar growth outcomes in children with IBD.

Impact of post-discharge phone calls on non-urgent hospital returns < 90 days following primary bariatric surgery.

INTRODUCTION: Quality of care delivery may improve patient outcomes post-bariatric surgery. We examined the quality of post-discharge phone calls (PhDC) to determine the impact on early (< 90 day) non-urgent hospital returns (NUHR) following primary bariatric surgery. METHODS: A retrospective review was performed on patients who underwent Roux-en-Y-gastric bypass (RYGB) or sleeve gastrectomy (SG) in 2019. Patients were compared between presence of care coaching (Jan-June 2019) versus no care coaching (July-Dec 2019). Baseline demographics, comorbidities, psychiatric history, and PhDC were collected. Index PhDCs were coded for completeness using a scoring system and rated by call quality. Patients were stratified into NUHR versus control group (Never returns [NR]). Primary analysis examined the impact of PhDC on NUHR. Sub-analysis examined the impact of call quality. Univariate analysis was performed using Chi-square or Fisher's exact tests. Multivariate analysis (MVA) was used to determine predictors of NUHR. A p-value of ≤ 0.05 was statistically significant. RESULTS: A total of 359 patients were included. Compared to the NR group (n = 294), NUHRs (n = 65) were more likely to be younger (41.3 + 12.1 versus 45.0 + 10.8 years, p = 0.024), with baseline anxiety (41.5% versus 23.5%, p = 0.003), and undergo RYGB (73.3% versus 57.8%, p = 0.031). There was a significant difference in number of PhDC in the NUHR and NR groups (p = 0.0206). Care-coached patients had significantly higher rates of high-quality phone calls (p < 0.0001) compared to non-care-coached patients. MVA demonstrated younger age (OR = 0.97, CI: 0.95-1.00; p = 0.023), anxiety (OR = 2.09, CI: 1.17-3.73; p = 0.012), RYGB (OR = 1.88, CI: 1.02-3.45; p = 0.042), and > 50% call quality versus no PhDC (OR = 0.45, CI: 0.25-0.83; p = 0.010) were independently associated with NUHRs. CONCLUSION: High-quality PhDCs may play a role in mitigating NUHRs. Care coaching represents a potential intervention to decrease high rates of NUHR in primary bariatric surgery patients.

Perceptually Discriminating the Highest Priority Alarms Reduces Response Time: A Retrospective Pre-Post Study at Four Hospitals.

OBJECTIVE: Reduce nurse response time for emergency and high-priority alarms by increasing discriminability between emergency and all other alarms and suppressing redundant and likely false high-priority alarms in a secondary alarm notification system (SANS). BACKGROUND: Emergency alarms are the most urgent, requiring immediate action to address a dangerous situation. They are clinician-triggered and have higher positive predictive value (PPV). High-priority alarms are automatically triggered and have lower PPV. METHOD: We performed a retrospective pre-post study, analyzing data 15 months before and 25 months after a SANS redesign was implemented in four hospitals. For emergency alarms, we incorporated digitized human speech to distinguish them from automatically triggered alarms, leaving their onset and escalation pathways unchanged. For automatically triggered alarms, we suppressed some by delaying initial onset and escalation by 20 s. We used linear mixed models to assess the change in response time, Fisher's exact test for the proportion of response times longer than 120 s, and control charts for process stability. RESULTS: Response time for emergency alarms decreased at all hospitals (main, from 26.91 s to 22.32 s, p < .001; cardiac, from 127.10 s to 52.43 s, p < .001; cancer, from 18.03 s to 15.39 s, p < .001). Improvements were sustained. Automatically triggered alarms decreased 25.0%. Response time for the three automatically triggered cardiac alarms increased at the four hospitals. CONCLUSION: Auditory sound disambiguation was associated with a sustained reduced nurse response time for emergency alarms, but suppressing some high-priority automatically triggered alarms was not. APPLICATION: Distinguishing and escalating urgent, actionable alarms with higher PPV improves response time.

Segmentectomy for clinical stage I non-small cell lung cancer: National benchmarks for nodal staging and outcomes by operative approach.

BACKGROUND: Segmentectomy is increasingly used for parenchyma sparing anatomical resection for small stage I non-small cell lung cancer (NSCLC). This study characterizes the national outcomes for lymph node assessment and perioperative outcomes of segmentectomy for clinical stage I NSCLC by robotic-assisted surgery (RATS), video-assisted thoracoscopic surgery (VATS), and open thoracotomy approach. METHODS: A retrospective cohort study was conducted of patients who underwent segmentectomy for clinical stage I NSCLC captured in the national Society of Thoracic Surgeons General Thoracic Surgery Database between years 2012 and 2018. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Lymph node (LN) staging and 30-day outcomes were compared by approach. RESULTS: A total of 3680 patients (VATS 61.9%, RATS 20%, open 18%) underwent segmentectomy. The IPTW adjusted rate of pathologic LN upstaging (pN1/pN2) was 6.2% (RATS 6.3%, VATS 5.6%, open 8.6%; P = .05). On multivariate analysis, there was no differences in pN1/N2 upstaging between RATS (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.44-1.49) or VATS (OR, 0.96; 95% CI, 0.57-1.63) with open segmentectomy. The RATS and VATS approach was associated with fewer postoperative events (RATS 31.3%, VATS 28.8%, open 38.3%; P < .001) and shorter length of stay (RATS 4.3 days, VATS 4.4 days, open 5.2 days; P < .001) as compared with thoracotomy. RATS segmentectomy-specific complications included a higher rate of pneumothorax after chest tube removal and discharge with chest tube. Major complications were lower after RATS and VATS as compared with open segmentectomy (RATS 5.9%, VATS 4.5%, open 7.2%; P = .028). CONCLUSIONS: Segmentectomy by VATS and robotic approach resulted in similar high rates of lymph node upstaging as a global marker of the quality of lymph node dissection and were associated with lower overall morbidity and shorter length of stay as compared with open thoracotomy. These national outcomes may serve as benchmarks for future comparative studies.

Antibody-suppressor CXCR5+ CD8+ T cellular therapy ameliorates antibody-mediated rejection following kidney transplant in CCR5 KO mice.

CCR5 KO kidney transplant (KTx) recipients are extraordinarily high alloantibody producers and develop pathology that mimics human antibody-mediated rejection (AMR). C57BL/6 and CCR5 KO mice (H-2b ) were transplanted with A/J kidneys (H-2a ); select cohorts received adoptive cell therapy (ACT) with alloprimed CXCR5+ CD8+ T cells (or control cells) on day 5 after KTx. ACT efficacy was evaluated by measuring posttransplant alloantibody, pathology, and allograft survival. Recipients were assessed for the quantity of CXCR5+ CD8+ T cells and CD8-mediated cytotoxicity to alloprimed IgG+ B cells. Alloantibody titer in CCR5 KO recipients was four-fold higher than in C57BL/6 recipients. The proportion of alloprimed CXCR5+ CD8+ T cells 7 days after KTx in peripheral blood, lymph node, and spleen was substantially lower in CCR5 KO compared to C57BL/6 recipients. In vivo cytotoxicity towards alloprimed IgG+ B cells was also reduced six-fold in CCR5 KO recipients. ACT with alloprimed CXCR5+ CD8+ T cells (but not alloprimed CXCR5- CD8+ or third-party primed CXCR5+ CD8+ T cells) substantially reduced alloantibody titer, ameliorated AMR pathology, and prolonged allograft survival. These results indicate that a deficiency in quantity and function of alloprimed CXCR5+ CD8+ T cells contributes to high alloantibody and AMR in CCR5 KO recipient mice, which can be rescued with ACT.

Incidence and Predictors of Inadvertent Dural Puncture After Percutaneous Spinal Cord Stimulation: A Retrospective Database Analysis.

OBJECTIVES: Inadvertent dural puncture (IDP) is a known complication associated with traditional neuraxial procedures; however, its characterization after percutaneous spinal cord stimulation (SCS) lead placement has yet to be clearly established in large population studies. This retrospective analysis aims to understand the incidence and associated characteristics of patients with IDP after percutaneous SCS lead placement. MATERIALS AND METHODS: The PearlDiver Mariner database of national all-payer claims was used to identify patients who received percutaneous SCS leads and had a claim for IDP (intraoperative IDP or postdural puncture headache [PDPH] claim) within 45 days. The primary outcome was to determine the overall incidence of IDP. Secondary outcomes included an evaluation of associated risk factors for IDP and treatments used in symptomatic management. RESULTS: A total of 90,952 patients who underwent percutaneous lead SCS placement were included. The incidence of IDP was 0.48% (436/90,952 patients). Older age (odds ratio [OR]: 0.96; 95% CI: 0.95-0.97; p < 0.0001) and male sex (OR: 0.66; 95% CI: 0.53-0.81; p < 0.001) had a lower odds of having a claim for IDP, whereas a history of IDP was associated with a higher OR (95% CI) by 13.72 times (10.72-17.58) (p < 0.0001). Of the IDP patients, 64% (277/436 patients) had a claim for a therapeutic blood patch. Discrepancy in type of claim for IDP was observed, with most being for PDPH. CONCLUSIONS: Our findings suggest that IDP after percutaneous SCS lead placement is an uncommon event; however, certain factors are associated with its development. Overall, early recognition of IDP after percutaneous SCS lead placement is imperative to facilitate the delivery of targeted treatments and prevent further harmful consequences to the patient.

Nomograms for predicting overall and recurrence-free survival after trimodality therapy for esophageal adenocarcinoma.

BACKGROUND: Locally advanced esophageal carcinoma is treated with neoadjuvant chemoradiation and esophagectomy. Patients may still experience recurrence and death despite undergoing potentially curative trimodality therapy. This study describes predictive nomograms for recurrence-free (RFS) and overall survival (OS) after the completion of trimodality therapy. METHODS: A total of 215 patients with esophageal adenocarcinoma underwent trimodality therapy from September 2010 to April 2018. Multivariate Cox proportional hazards regression models were used to create nomograms for OS and RFS. Kaplan-Meier survival curves were calculated for OS and RFS comparing high-risk and low-risk cohorts. RESULTS: On multivariate analysis, clinical N-stage, tumor differentiation, tumor regression grade, anastomotic leak, body mass index, age, and number of lymph nodes removed were predictive variables for overall survival. Clinical N-stage, tumor differentiation, tumor regression grade, anastomotic leak, age, and positive lymph nodes were significant predictors of RFS in a multivariate model. The nomogram for OS had good predictive ability (Harrell's Concordance index [C-index]: 0.71 [95% confidence interval {CI}: 0.66-0.76]). The nomogram for RFS also performed well (C-index: 0.70 [95% CI: 0.65-0.74]). CONCLUSION: Our nomograms can accurately predict OS and RFS after trimodality therapy and may provide guidance regarding adjuvant therapy and surveillance.

Racial disparities in provider recommendation for esophagectomy for esophageal carcinoma.

BACKGROUND: Racial disparities currently exist for the utilization rate of esophagectomy for Black patients with operable esophageal carcinoma. METHODS: A total of 37 271 cases with the American Joint Committee on Cancer clinical stage I, II, and III esophageal carcinoma that were reported to the National Cancer Database were analyzed between 2004 and 2016. A multivariable-adjusted logistic regression model was used to evaluate differences in the odds ratio of esophagectomy not being recommended based on race. Kaplan-Meier curves and log-rank tests were used to evaluate differences in overall survival. Propensity score methodology with inverse probability of treatment weighting (IPTW) was used to balance baseline differences in patient demographics. RESULTS: After IPTW adjustment, we identified 30 552 White patients and 3529 Black patients with clinical stage I-III esophageal carcinoma. Black patients had three times greater odds of not being recommended for esophagectomy (odds ratio: 3.03, 95% confidence interval: 2.67-3.43, p < 0.0001) compared to White patients. Black patients demonstrated significantly worse 3- and 5-year overall survival rates compared to White patients (log-rank p < 0.0001). CONCLUSION: Black patients with clinical stage I-III esophageal cancer were significantly less likely to be recommended for esophagectomy even after adjusting for baseline demographic covariates compared to White patients.

Enoxaparin Dose Requirements to Achieve Therapeutic Low-molecular-weight Heparin Anti-factor Xa Levels in Infants and Young Children.

INTRODUCTION: Enoxaparin is commonly used to treat pediatric thrombosis. Several small retrospective studies have suggested that infants and young children require higher enoxaparin doses to achieve therapeutic anti-factor Xa levels compared with adults. MATERIALS AND METHODS: This is a retrospective study of hospitalized children who received enoxaparin for the treatment of thrombosis at a free-standing children's hospital. The primary objective was to ascertain the enoxaparin dose required to achieve an anti-factor Xa level of 0.5 to 1.0 U/mL among 4 age groups in a large cohort of infants and young children between 60 days and 5 years of age. RESULTS: A total of 176 infants and children were evaluated. The majority of patients were less than 1 year of age (n=104). An inverse relationship between enoxaparin dose needed to achieve therapeutic anti-factor Xa levels and patient age was noted, particularly in the first year of life. Patients who were 60 days to less than 7 months at the time of enoxaparin initiation (n=73) required the highest mean dose among the age groups at 1.73 mg/kg subcutaneously every 12 hours (P<0.0001). CONCLUSION: Infants and young children require higher doses of enoxaparin to achieve therapeutic anti-factor Xa levels compared with adults.

Use of the MMPI-2 personality profile in predicting 30-day ED-visits and readmissions following primary bariatric surgery.

BACKGROUND: Minnesota Multiphasic Personality Inventory-2 (MMPI-2) is used for psychological screening of bariatric surgery (BS) candidates. To date, no studies have analyzed the relationship between MMPI-2 and early returns to hospital. The aim of this study was to determine whether high T scores on the MMPI-2 clinical scales were associated with early return to hospital after primary bariatric surgery. METHODS: Patients who completed an MMPI-2 evaluation, undergoing primary BS from 2014 to 2016 were evaluated. T score for the tested scales were collected and stratified into a high T score (T > 65) vs not (T < 65). The optimal 'cut-point' (specific number of high T scores predicting likelihood for 30-day ED-visit/hospital readmission) was calculated using Youden's Index (J) = Max(c) [sensitivity (c) + specificity (c) - 1], where c = number of scales with a T score > 65. Patients were stratified based on the optimal cut-point which was determined to be ≥ 4 high T scores. Univariate and multivariate logistic regression analyses were used to identify differences between groups and predictors for early ED-visits and hospital readmissions. RESULTS: 375 patients had psychological evaluations available for review. Patients were divided into those with ≥ 4 high T scores (Scr(≥4); n = 86) versus not (Scr (<4); n = 289). Multivariate analysis showed Scr(≥ 4) (aOR 2.99, CI 1.20-7.47; p = 0.019), bipolar disorder (aOR 4.82, CI 1.25-18.83; p = 0.022), and urgent hospital complications (aOR 6.81, CI 2.02-22.91; p = 0.002), were significant independent predictors of 30-day readmissions. Early ED-visits were significantly predicted by public insurance (aOR 3.30, CI 1.22-8.91; p = 0.019), but the effect of the Scr(≥4) profile (aOR 2.42, CI 0.97-6.09; p = 0.06), while influential, did not reach significance. CONCLUSION: Differences in personality traits may be associated increased 30-day readmissions following primary bariatric surgery. Our study represents a novel application of the MMPI-2.

Evaluation of the Efficacy of Enoxaparin in the Neonatal Intensive Care Unit.

OBJECTIVE: This article evaluates the efficacy of enoxaparin when targeting anti-factor Xa levels of 0.5 to 1 units per milliliter in the neonatal intensive care unit. STUDY DESIGN: This is a retrospective chart review of 45 neonates receiving enoxaparin for the treatment of venous thromboembolism. Enoxaparin dosing and corresponding anti-factor Xa levels were collected. Time to resolution of clot was confirmed by imaging and compared between clots in various locations. RESULTS: The median time to clot resolution was 76 days (interquartile range 40-91 days). Clot location, postnatal age, and sex at the clot onset were significantly associated with time to clot resolution in a multivariable Cox model (p-value: 0.03, 0.03, and < 0.01, respectively). Of the 54 patients analyzed for safety, 5 patients (9.3%) experienced bleeding events resulting in the discontinuation of enoxaparin. CONCLUSION: Based on our findings, 50% of all patients evaluated, regardless of thrombus location, achieved resolution within the first 76 days of therapy. Clots located in the extremities tended to resolve sooner, hence earlier reimaging should be considered.

Economic impact of pharmacist interventions in pediatric ambulatory care clinics.

OBJECTIVES: Ambulatory care pharmacists have a unique opportunity to identify and prevent adverse drug events (ADEs) throughout a patient's treatment course. These interventions can reduce unexpected clinic visits or hospitalizations, which may lead to decreased health care costs. However, research on this topic has not been conducted in the pediatric population. This study explored the economic impact of pharmacist interventions related to ADEs in pediatric ambulatory care clinics. The primary objective was to determine the total cost avoidance of pharmacist interventions associated with the prevention or management of ADEs in pediatric ambulatory care clinics. The secondary objectives were to describe and quantify pharmacist interventions related to the prevention and management of ADEs in pediatric ambulatory care clinics. METHODS: Pharmacist interventions from pediatric ambulatory care clinics were collected from an electronic health record. These interventions were categorized into 1 of 4 categories: Drug interaction, drug not indicated, prevent or manage ADE, or prevent or manage drug allergy. A review panel consisting of ambulatory care pharmacists reviewed the interventions. The expected probability of the event occurring was classified according to the Nesbit method (0-0.6), and the level of care necessary to treat the potential ADE was determined. The levels of care included hospitalization, ambulatory care, and self-care. The cost avoidance associated with each prevented ADE was calculated by multiplying the probability of the ADE occurring by the average charge of the expected level of care. RESULTS: Of the 8755 interventions documented, 212 were included, leading to a total cost avoidance of $307,210 (range $76,802-$1,071,053). The estimated cost avoidance from each ADE subtype was $128,283 from drug interaction, $20,727 from drug not indicated, $157,993 from prevent or manage ADE, and $207 from prevent or manage drug allergy. CONCLUSION: Pediatric ambulatory care pharmacists optimize health care cost savings through the prevention and management of ADEs as integrated members of the health care team.