CD5 B-Cell Predominant Primary Immunodeficiency: Part of the Spectrum of MAGT1 Deficiency.

Background: Selective anti-polysaccharide antibody deficiency (SPAD) with CD5 B-cell predominance and autoimmune phenomena was identified in a male cohort first reported by Antall et al in 1999. The phenotypically likewise and genotypically identical X-linked immunodeficiency with magnesium defect, Epstein-Barr Virus infection, and neoplasia (XMEN) disease was defined as a novel primary immunodeficiency (PID) in 2011. Recent studies of the magnesium transporter 1 (MAGT1) gene mutation reveal glycosylation defects contributing to more phenotypic variance than the "XMEN" title pathologies. The updated title, "X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect," was proposed in 2020. Objectives: To reflect the patient population more accurately, a prospective classification update may consider MAGT1 glycobiological errors contributing to phenotypic variance but also pre-genetic testing era reports with CD5 B-cell predominance. Methods: Patient 1 from Antall et al presented at 28 years of age for further immunological evaluation of his CD5/CD19 B-cell predominance diagnosed at 5 years old. Design: Immune re-evaluation done through flow cytometry and next-generation sequencing. Results: Flow cytometry B-cell phenotyping revealed persistent CD5+CD19+ (93%). Flow cytometric histogram quantified reduced activator CD16+CD56+ natural killer and CD8+ T-cell receptor, Group 2, Member D (NKG2D) glycoprotein expression. A c.923-1_934 deletion loss of function mutation was identified in the MAGT1 gene. Conclusion: We suggest the novel PID XMEN, based on its CD5 B-cell predominance, had been discovered and reported over a decade earlier as CD5+ PID based on the MAGT1 mutation found in the same. We encourage consideration of combining these labels and recent findings to offer the most accurate classification of this disease.

The effect of intraoperative positive end expiratory pressure and tidal volume on postoperative acute kidney injury after orthopedic surgery.

BACKGROUND: To test whether higher intraoperative PEEP levels and/or higher TV levels are associated with higher incidence of postoperative AKI within the first postoperative week, in adult patients having orthopedic surgeries under general anesthesia. METHODS: We conducted a sub analysis of a non-randomized alternating intervention cross over study performed in patients undergoing orthopedic surgery under general anesthesia at Cleveland Clinic, Cleveland, OH. We included four different combinations of PEEP (5 or 8 cm H2 O) and TV (6 or 10 mL/kg of PBW) that alternated each week in the six orthopedic operating rooms. Our primary outcome was postoperative AKI defined by the KDIGO criteria with baseline creatinine as the closest preoperative value to the time of surgery obtained within 30 days and postoperative value as the highest creatinine value within 7 days after surgery. Secondary outcome was the maximum postoperative in-hospital creatinine level within seven postoperative days. MAIN RESULTS: A total of 1933 patients were included in the analysis. The incidence of AKI was 6.8% in the study population and similar in high TV versus low TV group and high PEEP versus low PEEP group. Neither TV nor PEEP significantly impacted AKI incidence. The estimated odds ratio of AKI comparing TV = 6 mL/kg to TV = 10 mL/kg was 0.96 (97.5% CI: 0.63, 1.46; p = .811); while the estimated odds ratio of AKI comparing PEEP = 5cm H2 O to PEEP = 8cm H2 O was 0.92 (97.5% CI: 0.60, 1.39; p = .623). No interaction was found between TV and PEEP on AKI. Additionally, neither TV nor PEEP had a significant effect on the seven postoperative day creatinine levels. CONCLUSION: Higher levels of PEEP or TV during mechanical ventilation in adult patients undergoing orthopedic surgeries under general anesthesia do not increase the odds of developing postoperative AKI within the narrow limits studied.

Effect of seasons on delirium in postoperative critically ill patients: a retrospective analysis

Abstract Background and objectives Postoperative delirium is common in critically ill patients and is known to have several predisposing and precipitating factors. Seasonality affects cognitive function which has a more dysfunctional pattern during winter. We, therefore, aimed to test whether seasonal variation is associated with the occurrence of delirium and hospital Length Of Stay (LOS) in critically ill non-cardiac surgical populations. Methods We conducted a retrospective analysis of adult patients recovering from non-cardiac surgery at the Cleveland Clinic between March 2013 and March 2018 who stayed in Surgical Intensive Care Unit (SICU) for at least 48 hours and had daily Confusion Assessment Method Intensive Care Unit (CAM-ICU) assessments for delirium. The incidence of delirium and LOS were summarized by season and compared using chi-square test and non-parametric tests, respectively. A logistic regression model was used to assess the association between delirium and LOS with seasons, adjusted for potential confounding variables. Results Among 2300 patients admitted to SICU after non-cardiac surgeries, 1267 (55%) had postoperative delirium. The incidence of delirium was 55% in spring, 54% in summer, 55% in fall and 57% in winter, which was not significantly different over the four seasons (p= 0.69). The median LOS was 12 days (IQR = [8, 19]) overall. There was a significant difference in LOS across the four seasons (p= 0.018). LOS during summer was 12% longer (95% CI: 1.04, 1.21; p= 0.002) than in winter. Conclusions In adult non-cardiac critically ill surgical patients, the incidence of postoperative delirium is not associated with season. Noticeably, LOS was longer in summer than in winter.

Effect of seasons on delirium in postoperative critically ill patients: a retrospective analysis.

BACKGROUND AND OBJECTIVES: Postoperative delirium is common in critically ill patients and is known to have several predisposing and precipitating factors. Seasonality affects cognitive function which has a more dysfunctional pattern during winter. We, therefore, aimed to test whether seasonal variation is associated with the occurrence of delirium and hospital Length Of Stay (LOS) in critically ill non-cardiac surgical populations. METHODS: We conducted a retrospective analysis of adult patients recovering from non-cardiac surgery at the Cleveland Clinic between March 2013 and March 2018 who stayed in Surgical Intensive Care Unit (SICU) for at least 48 hours and had daily Confusion Assessment Method Intensive Care Unit (CAM-ICU) assessments for delirium. The incidence of delirium and LOS were summarized by season and compared using chi-square test and non-parametric tests, respectively. A logistic regression model was used to assess the association between delirium and LOS with seasons, adjusted for potential confounding variables. RESULTS: Among 2300 patients admitted to SICU after non-cardiac surgeries, 1267 (55%) had postoperative delirium. The incidence of delirium was 55% in spring, 54% in summer, 55% in fall and 57% in winter, which was not significantly different over the four seasons (p = 0.69). The median LOS was 12 days (IQR = [8, 19]) overall. There was a significant difference in LOS across the four seasons (p = 0.018). LOS during summer was 12% longer (95% CI: 1.04, 1.21; p = 0.002) than in winter. CONCLUSIONS: In adult non-cardiac critically ill surgical patients, the incidence of postoperative delirium is not associated with season. Noticeably, LOS was longer in summer than in winter.

Wearable device for prevention of postoperative and post-discharge hypoxemia: A randomized pilot trial.

BACKGROUND: The Oxalert Enhanced Pulse Oximeter (EPO) is a wearable device that detects and alerts patients to hypoxemia. In a preplanned pilot trial, we estimated the effect of continuous saturation monitoring with patient alerts on in-hospital and post-discharge saturation; we further assessed the feasibility of the intervention. METHODS: Noncardiac surgical patients were randomized to either the Oxalert with patient alerts (Monitor + Alert, N = 25) or the Oxalert without patient alerts (Monitor Only, N = 24). Monitoring continued during hospitalization for up to 6 days and for 24 h after hospital discharge. Patients in each group were compared on time-weighted average (TWA) SpO2 <90% (%) and area under SpO2 <90% (% * min) in-hospital and after discharge using the Wilcoxon rank sum test, with the treatment effect median difference and 95% confidence interval (CI) estimated using the Hodges-Lehmann estimator of location shift. RESULTS: We enrolled ≥2 patients per week, for a total of 49 patients in whom recording were obtained for a median [quartiles] of 91 [85, 95]% of the time in hospital. In-hospital, TWA SpO2 <90% was a median [quartiles] of 0.11 [0.03, 0.25]% for Monitor + Alert and 0.29 [0.04, 0.71]% for Monitor-Only patients, with estimated median difference (95% CI) of -0.1 (-0.4, 0)%, p = .120. In hospital, the area under the curve (AUC) SpO2 <90% was a median [quartiles] of 635 [204, 1513] % * min for Monitor + Alert and 1260 [117, 5278] % * min for Monitor-Only patients, with estimated median difference (95% CI) of -407 (-1816, 208) % * min, p = .349. Post-discharge, the estimated median difference (95% CI) was only -0.1 (-0.2, 0) %, p = .307. CONCLUSIONS: The Oxalert system was well tolerated in both groups and enrollment was strong. Patients randomized to active Oxalert systems experienced half as many postoperative desaturation events while hospitalized, although the difference was not statistically significant in this small pilot trial. In contrast, the Oxalert system did not reduce post-discharge desaturation. Detecting postoperative deterioation in surgical patients after they arrive on regular hospital wards, and even after they have been discharged home, can potentially facilitate necessary "rescue" interventions. Wearable devices assessing vital signs, including oxygenation, are a practical requirement. In this pilot study, a wearable pulse oximeter, with and without hypoxemia alarms, was tested for feasibility and acceptability for signal collection in postoperative cases, including at home. Results indicate that a full-scale trial is warranted to test for possible clinical benefit with this type of "wearable" where late postoperative hypoxia could be a concern. The trial was registered at ClincialTrial.gov (NCT04453722).

Dexamethasone as an Analgesic Adjunct for Postcesarean Delivery Pain: A Randomized Controlled Trial.

OBJECTIVES: Dexamethasone has been shown to have analgesic properties in the general surgical population. However, the analgesic effects for women that undergo cesarean deliveries under spinal anesthesia remain unclear and may be related to the timing of dexamethasone administration. We hypothesized that intravenous dexamethasone administered before skin incision would significantly reduce postoperative opioid consumption at 24 h after cesarean delivery under spinal anesthesia with intrathecal morphine. METHODS: Women undergoing elective cesarean deliveries under spinal anesthesia were randomly assigned to receive 8 mg of intravenous dexamethasone or placebo prior to skin incision. Both groups received a standardized spinal anesthetic and multimodal postoperative analgesic regime. The primary outcome was cumulative opioid consumption at 24 h. Secondary outcomes included cumulative opioid consumption at 48 h, time to first analgesic request, and pain scores at rest and on movement at 2, 24, and 48 h. RESULTS: 47 patients were analyzed-23 subjects that received dexamethasone and 24 subjects that received placebo. There was no difference in the median (Q1, Q3) cumulative opioid consumption in the first 24 hours following cesarean delivery between the dexamethasone group {15 (7.5, 20.0) mg} and the placebo group {13.75 (2.5, 31.25) mg} (P=0.740). There were no differences between the groups in cumulative opioid consumption at 48 h, time to first analgesic request, and pain scores. CONCLUSIONS: Intravenous dexamethasone 8 mg administered prior to skin incision did not reduce the opioid consumption of women that underwent cesarean deliveries under spinal anesthesia with intrathecal morphine and multimodal postoperative analgesic regimen.

Failure to detect ward hypoxaemia and hypotension: contributions of insufficient assessment frequency and patient arousal during nursing assessments.

BACKGROUND: Postoperative hypotension and hypoxaemia are common and often unrecognised. With intermittent nursing vital signs, hypotensive or hypoxaemic episodes might be missed because they occur between scheduled measurements, or because the process of taking vital signs arouses patients and temporarily improves arterial blood pressure and ventilation. We therefore estimated the fraction of desaturation and hypotension episodes that did not overlap nursing assessments and would therefore usually be missed. We also evaluated the effect of taking vital signs on blood pressure and oxygen saturation. METHODS: We estimated the fraction of desaturated episodes (arterial oxygen saturation <90% for at least 90% of the time within 30 continuous minutes) and hypotensive episodes (MAP <70 mm Hg for 15 continuous minutes) that did not overlap nursing assessments in patients recovering from noncardiac surgery. We also evaluated changes over time before and after nursing visits. RESULTS: Among 782 patients, we identified 878 hypotensive episodes and 2893 desaturation episodes, of which 79% of the hypotensive episodes and 82% of the desaturation episodes did not occur within 10 min of a nursing assessment and would therefore usually be missed. Mean BP and oxygen saturation did not improve by clinically meaningful amounts during nursing vital sign assessments. CONCLUSIONS: Hypotensive and desaturation episodes are mostly missed because vital sign assessments on surgical wards are sparse, rather than being falsely negative because the assessment process itself increases blood pressure and oxygen saturation. Continuous vital sign monitoring will detect more disturbances, potentially giving clinicians time to intervene before critical events occur.

Ethnic Differences in Analgesic Efficacy and Safety of Liposomal Bupivacaine Among Asian and Caucasian Surgical Patients: A Retrospective Matched-Cohort Analysis.

BACKGROUND: Extended-release local anesthetics allow for prolonged analgesia after a single administration. Although Asians demonstrate different pain thresholds than Caucasians, whether they have different postoperative local anesthetic analgesic effects has not been elucidated. OBJECTIVE: We aimed to compare the postoperative analgesic efficacy of liposomal bupivacaine on Asian and Caucasian adults, and the incidence of local anesthetic systemic toxicity (LAST) syndrome. METHODS: We conducted a retrospective, assessor-blinded cohort study of adult patients who received liposomal bupivacaine for surgery between 2012 and 2018. Asians and Caucasians were matched in a 1:1 ratio by clinical characteristics and surgery type. The primary outcome was pain management, defined as average pain score and opioid consumption during the initial 72 postoperative hours. The secondary outcome was the incidence of LAST syndrome. Reviewers were blinded to the ethnicity of the patient. RESULTS: After 1:1 propensity score matching, 130 Asians and 129 Caucasians were analyzed. All confounding variables were balanced, except for higher body mass index in the Asian group. Pain scores were lower (adjusted mean difference of -0.50 [97.5% CI, -0.98, -0.01]; superiority p = 0.011) and opioid consumption was not greater (geometric means ratio, 0.61 [97.5% CI, 0.36, 1.04]; non-inferiority p ＜ 0.001) in Asian patients compared to Caucasian patients. Only one Caucasian patient was judged as having a potential case of LAST syndrome. The length of hospital stay and the incidence of additional complications were not different between the groups. CONCLUSION: Asian adults receiving liposomal bupivacaine as part of multimodal perioperative analgesia demonstrated lower pain scores compared to matching Caucasians, despite not having greater opioid consumption.

N-Methyl-D-Aspartate Antagonists and Steroids for the Prevention of Persisting Post-Surgical Pain After Thoracoscopic Surgeries: A Randomized Controlled, Factorial Design, International, Multicenter Pilot Trial.

PURPOSE: We conducted a feasibility 2×2 factorial trial comparing N-methyl-D-aspartate (NMDA) antagonists (intravenous ketamine and oral memantine) versus placebo and intravenous steroids versus placebo, in patients having elective video-assisted thoracic surgery lobectomies, at St. Joseph's Hamilton, Canada, and Cleveland Clinic, Cleveland, USA. Our feasibility objectives were: 1) recruitment rate/week; 2) recruitment of ≥90% of eligible patients; and 3) >90% follow-up. Secondary objectives were incidence and intensity of persistent post-surgical pain (PPSP) and other clinical and safety outcomes. METHODS: Using computerized randomization, patients were allocated to one of four groups: NMDA active with steroid placebo; NMDA placebo with steroid active; both NMDA and steroid active; both NMDA and steroid placebo. Patients, health providers, and data analysts were blinded to allocation. Patients were followed for 3 months after randomization. RESULTS: The trial was initiated in May 2017 at Hamilton and, after subsequent regulatory and ethics approval, in April 2018 at Cleveland. The trial had to be stopped after only 1 month of recruitment in Cleveland because the packaged study medications (memantine) expired and we were unable to procure the dosage required. Among 41 eligible patients, 27 (66%) were randomized. The recruitment rate/week was 0.63, 95% confidence interval (CI): 0.47-0.79 in Hamilton; and 1, 95% CI: 0.83-1.17 in Cleveland. Follow-up was complete for all 24 patients (100%) in Hamilton, and 3 of 4 patients in Cleveland. In total, only 4 patients (15%), and 2 patients (7%) had persistent pain at rest and with movement, respectively. There were no significant differences between groups for other outcomes. CONCLUSION: The trial had to be stopped prematurely due to non-availability of study medications. Trial feasibility objectives of recruiting 90% of eligible patients and recruiting at least one patient/week per site were not met. Consideration for protocol changes will be necessary for the full trial. TRIAL REGISTRATION: NCT02950233.

Incidence of adverse events attributable to bupivacaine liposome injectable suspension or plain bupivacaine for postoperative pain in pediatric surgical patients: A retrospective matched cohort analysis.

BACKGROUND: Surgical wound infiltration with local anesthetics is common as part of multimodal analgesia and enhanced recovery pathways in pediatric surgical patients. Liposomal bupivacaine can provide up to 92 hours of pain relief, and was approved by the U.S Food and Drug Administration for local infiltration in adults. It is also commonly used by pediatric surgeons, but its safety profile in this age group has not been described. AIMS: The aim of this study was to describe the incidence of local anesthetic systemic toxicity syndrome in pediatric surgical patients receiving liposomal bupivacaine compared to plain bupivacaine for surgical wound infiltration. METHODS: We conducted a retrospective, single center, assessor blinded cohort study of pediatric surgical inpatients having open or laparoscopic surgery in the Cleveland Clinic between 2013 and 2017 and receiving wound infiltration with local anesthetics. We compared the incidence of local anesthetic systemic toxicity among those who received any dose of liposomal bupivacaine and those who received plain bupivacaine. Groups were matched 1:2 according to procedure type, age, and physical status score. Local anesthetic systemic toxicity was primarily defined as at least two signs or symptoms possibly related to anesthetic toxicity, as judged by two independent adjudicators blinded to the type of local anesthetic. A sensitivity analysis compared the incidence of a single sign/symptom possibly related to anesthetic toxicity. RESULTS: A total of 924 surgical cases were included in the final analysis (356 liposomal bupivacaine and 568 plain bupivacaine cases). The primary outcome did not occur in any patient. The sensitivity analysis found three cases in the liposomal bupivacaine group and two cases in the plain bupivacaine group having a single sign/symptom possibly related to local anesthetic administration (relative risk 2.4, 95% CI 0.4-14.0, P = 0.38). CONCLUSION: In a cohort of pediatric surgical patients receiving wound infiltration with either plain or liposomal bupivacaine, we identified no cases of local anesthetic systemic toxicity syndrome, and only few patients with any sign or symptom that could potentially be related to local anesthetic toxicity.