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Background: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown.Methods: In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis.Results: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32).Conclusions: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.). [ABSTRACT FROM AUTHOR]

Background: Patient perception of physician compassion may be associated with improved health outcomes, yet it is unclear whether it is associated with postoperative pain reduction or improved patient experience metrics in same-day surgery patients. We hypothesized that higher anesthesiologist compassion during the preanesthesia interview, rated by patients, is associated with lower postoperative pain via the anxiety pathway in same-day surgery patients. We also performed exploratory correlation analysis to assess whether compassion was associated with less opioid consumption and improved patient experience in same-day surgery patients., Methods: We conducted a single-center, prospective, observational cohort study in American Society of Anesthesiologists (ASA) physical status I to III patients scheduled to undergo same-day surgery with anesthesia. Compassion was scored using a validated 5-item tool. State anxiety (SA) and trait anxiety (TA) were measured using the State-Trait Anxiety Inventory. Pain scores were obtained using a 0 to 10 Likert scale. Daily opioid use was recorded. Patient experience was assessed using the Consumer Assessment of Healthcare Providers and Systems Outpatient and Ambulatory Surgery Survey (OAS CAHPS) and the Surgical Care CAHPS. Mediation analysis was used to assess the association between compassion and pain scores via the anxiety pathway. Spearman correlation was performed to test for association between the compassion score and the secondary outcomes., Results: A total of 147 subjects completed the study with a median age of 50 years and 81% female. Fifty percent underwent breast surgery, 35% abdominal surgery, and the rest underwent gynecological and urological surgeries. The median (Q1-Q3) postoperative pain scores on postoperative days 0 and 3 days later were 4 (1.5-6) and 3 (1-5), respectively.Mediation analysis results showed a same-day anxiety-mediated effect (95% confidence interval [CI]) of compassion on pain of -0.08 (-0.13 to -0.02), attributing to 9% of the total effect. On postoperative day 0, an increase in compassion was associated with a significant average drop in pain of between 0.02 and 0.13. In addition, higher compassion was correlated with better patient experience metrics (ρ= -0.53 [95% CI, -0.64 to -0.39])., Conclusions: The study results suggest that an anxiety-mediated pathway exists through which compassionate care may help improve the patient's perception of postoperative pain on the day of surgery (before discharge from the hospital). Higher compassion was also associated with better patient experience metrics., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Objective: Dorsal root ganglion stimulation (DRG-S) is a novel therapy to treat chronic pain. It has shown efficacy when delivered intermittently, suggesting a delayed washout effect exists. To measure the washout period, and to determine whether there are differences in washout times among different types of treated pain, we measured the time for pain to return at the end of the patients' one-week DRG stimulation trials., Materials and Methods: Patients who completed a successful DRG-S trial were included. The times until 25% (t25) and 90% (t90) of baseline pain level returned were recorded. The patients were divided into neuropathic, nociceptive, and mixed pain groups for subgroup comparison. t25 and t90 were plotted in the entire cohort and subgroups using reverse Kaplan-Meier plots (failure curves) and compared using a log-rank test., Results: In total, 29 consecutive patients were included. Median t25 and t90 times were 7.1 and 19.5 hours, respectively. Median (interquartile range) times were longest for the nociceptive pain group (n = 17) and shortest for the neuropathic pain group (n = 6), with the mixed-pain group (n = 6) in between (t25: 7.1 [1.7-19.4], 3.40 [1.4-8.4], and 5.7 [0.8-17.6]; t90, 22.0 [10.7-71.0], 7.6 [3.6-19.8], and 20.9 [14.2-31.2], respectively). t90 times differed significantly by pain type (p = 0.040)., Conclusions: This study showed a prolonged washout period after cessation of DRG-S therapy. Washout times vary according to pain type. The observed effects are possibly due to long-term depression of pain signaling and could allow the implementation of alternative stimulation strategies with DRG-S. Further investigations evaluating DRG-S washout times are warranted., Competing Interests: Conflict of Interest Kenneth B. Chapman reports a relationship with Abbott that includes funding grants. The remaining authors reported no conflict of interest., (Copyright © 2024 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Introduction For peripheral nerve blocks, using either the liposomal formulation of bupivacaine or plain bupivacaine with epinephrine and dexamethasone as an adjuvant has been shown to improve postoperative pain scores. In a single-blinded, randomized controlled study of patients undergoing robotic-assisted thoracoscopic surgery, we determined if bupivacaine with epinephrine and dexamethasone was noninferior to liposomal bupivacaine mixed with plain bupivacaine when administered intraoperatively as an intercostal nerve block (INB). Methods A total of 34 patients undergoing robotic-assisted thoracoscopic surgery were randomized to receive one of two injectate mixtures during their intraoperative INB. Group LB was administered 266 mg of 13.3 mg/mL liposomal bupivacaine with 24 mL of 0.5% plain bupivacaine, while Group BD was given 42 mL of 0.5% bupivacaine with epinephrine and 8 mg of dexamethasone. The primary outcomes were mean postoperative numerical pain ratings and mean postoperative opioid analgesic requirements. Secondary outcomes included adjuvant pain medication consumption, hospital length of stay, and total opioid use in oral morphine equivalents. Results Group LB exhibited no significant difference in pain scores (p = 0.437) and opioid analgesic requirement (p = 0.095) within the 72-hour postoperative period when compared to Group BD. The median total postoperative opioid requirement was 90 mg in Group LB, compared to 45 mg in Group BD. There were no significant differences in the use of postoperative adjuvant pain medications (gabapentin, p = 0.833; acetaminophen, p = 0.190; ketorolac, p = 0.699). Hospital length of stay did not differ between the groups. Conclusions INBs with the addition of dexamethasone as an adjuvant to 0.5% bupivacaine with epinephrine provided noninferior postoperative analgesia compared to liposomal bupivacaine mixed with plain 0.5% bupivacaine., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Cooper University Healthcare IRB issued approval 18-039. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ganguly et al.)

Background: Lead anchoring has previously been shown to reduce the rate of dorsal root ganglion stimulation (DRG-S) lead migration. The aim of this study was to assess longer-term follow-up and consistency of lead migration prevention with lead anchoring in a new cohort of patients., Methods: We performed a retrospective chart review from September 2017 to November 2022 of all patients who had DRG-S implants at our institute to identify the number of lead migrations that occurred over this period. The first cohort consisted of patients reported on in a previous publication (implanted from September 2017 through September 2020) subdivided into unanchored or anchored lead groups. The second cohort consisted of patients implanted during or after October 2020 who were not previously reported on for whom leads were anchored using silastic anchoring only., Results: At the November 2022 data cutoff, in the initial cohort, 8 migrations had occurred in unanchored leads over an average follow-up of 49 months, equating to a migration rate of 9.1% per lead. Patients with anchored leads in the initial cohort experienced 2 migrations over an average follow-up of 38 months (0.7% migration rate per lead). There were no new lead migrations in these groups over the extended follow-up reported here. The migration rate in the new cohort was similar, with 1 migration over an average follow-up of 13 months (0.5% migration rate per lead)., Conclusion: These results underscore the necessity of anchor placement during DRG-S lead implantation to prevent lead migration., (© 2023 World Institute of Pain.)

A 67-year-old man presented with severe 9 of 10 intractable pain of the left shoulder joint after arthroplasty and revision surgeries, with associated weakness, atrophy, and limited range of motion in all directions. Dorsal root ganglion stimulation (DRG-S) at the left C4, C5, and C6 levels was used after failed conservative and interventional measures, resulting in significant improvement in pain, function, and quality of life measures through 6 months postimplantation. Larger studies should examine if DRG-S is effective in treating chronic arthritic joint pain as well as chronic postsurgical pain of the shoulder that is not predominantly neuropathic., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Vitamin D insufficiency has been linked to multiple conditions including bone disease, respiratory disease, cardiovascular disease, diabetes, and cancer. Observational studies indicate lower healthcare costs and healthcare utilization with sufficient vitamin D levels. The secondary aims of our previously published pragmatic clinical trial of vitamin D3 supplementation were comparisons of healthcare costs and healthcare utilization. Comparisons were made between the vitamin D3 at 5000 IU supplementation group and a non-supplemented control group. Costs of care between the groups differed but were not statistically significant. Vitamin D3 supplementation reduced healthcare utilization in four major categories: hospitalizations for any reason (rate difference: -0.19 per 1000 person-days, 95%-CI: -0.21 to -0.17 per 1000 person-days, p < 0.0001); ICU admissions for any reason (rate difference: -0.06 per 1000 person-days, 95%-CI: -0.08 to -0.04 per 1000 person-days, p < 0.0001); emergency room visits for any reason (rate difference: -0.26 per 1000 person-days, 95%-CI: -0.46 to -0.05 per 1000 person-days, p = 0.0131; and hospitalizations due to COVID-19 (rate difference: -8.47 × 10 -3 per 1000 person-days, 95%-CI: -0.02 to -1.05 × 10 -3 per 1000 person-days, p = 0.0253). Appropriately powered studies of longer duration are recommended for replication of these utilization findings and analysis of cost differences.

Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19., Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization., Results: Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82)., Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course., Competing Interests: Drs Senefeld, Carter, Joyner, Fairweather, Bruno, and Wright reported being investigators in the US Expanded Access Program of COVID-19 convalescent plasma. Drs Paneth, Casadevall, and Joyner reported serving as leadership for the COVID-19 Convalescent Plasma Project outside the submitted work., (© 2023 The Authors.)

Introduction: Designing and conducting clinical trials is challenging for some institutions and researchers due to associated time and personnel requirements. We conducted recruitment, screening, informed consent, study product distribution, and data collection remotely. Our objective is to describe how to conduct a randomized clinical trial using remote and automated methods., Methods: A randomized clinical trial in healthcare workers is used as a model. A random group of workers were invited to participate in the study through email. Following an automated process, interested individuals scheduled consent/screening interviews. Enrollees received study product by mail and surveys via email. Adherence to study product and safety were monitored with survey data review and via real-time safety alerts to study staff., Results: A staff of 10 remotely screened 406 subjects and enrolled 299 over a 3-month period. Adherence to study product was 87%, and survey data completeness was 98.5% over 9 months. Participants and study staff scored the System Usability Scale 93.8% and 90%, respectively. The automated and remote methods allowed the study maintenance period to be managed by a small study team of two members, while safety monitoring was conducted by three to four team members. Conception of the trial to study completion was 21 months., Conclusions: The remote and automated methods produced efficient subject recruitment with excellent study product adherence and data completeness. These methods can improve efficiency without sacrificing safety or quality. We share our XML file for researchers to use as a template for learning purposes or designing their own clinical trials., Competing Interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support by a grant from the Won Sook Chung Foundation; PJL and BB are employed full-time by the Won Sook Chung Foundation. TLB and KQN are employed part-time by the Won Sook Chung Foundation. TC, HG, DT, and MAM were employed part-time by the Won Sook Chung Foundation during the study. TC holds the position of research coordinator at Cooper University Health Care; this position is fully funded by the Won Sook Chung Foundation. The president of the Won Sook Chung Foundation, MKC, was not involved in the study design, subject consenting, data collection and analysis, decision to publish, or preparation of the manuscript. MKC was involved in the conceptualization of the study and review of the manuscript. TLB and KH are members of the Cooper University Hospital Institutional Review Board (CUH IRB) in the roles of unaffiliated scientist and affiliated biostatistician, respectively. Per the CUH IRB SOPs and HHS federal regulation 45 CFR 46.107(e), TLB and KH left the meeting before any motions were made on this study; were not present for any final discussions regarding the study; and did not participate on any votes regarding this study. This is reflected in the CUH IRB meeting minutes., (© The Author(s) 2023.)

Competing Interests: Competing interests: None declared.

Vitamin D supplementation has been shown to reduce the incidence of acute respiratory infections in populations at risk. The COVID-19 pandemic has highlighted the importance of preventing viral infections in healthcare workers. The aim of this study was to assess the hypothesis that vitamin D3 supplementation at 5000 IU daily reduces influenza-like illness (ILI), including COVID-19, in healthcare workers. We conducted a prospective, controlled trial at a tertiary university hospital. A random group of healthcare workers was invited to receive 5000 IU daily vitamin D3 supplementation for nine months, while other random healthcare system workers served as controls. All healthcare workers were required to self-monitor and report to employee health for COVID-19 testing when experiencing symptoms of ILI. COVID-19 test results were retrieved. Incidence rates were compared between the vitamin D and control groups. Workers in the intervention group were included in the analysis if they completed at least 2 months of supplementation to ensure adequate vitamin D levels. The primary analysis compared the incidence rate of all ILI, while secondary analyses examined incidence rates of COVID-19 ILI and non-COVID-19 ILI. Between October 2020 and November 2021, 255 healthcare workers (age 47 ± 12 years, 199 women) completed at least two months of vitamin D3 supplementation. The control group consisted of 2827 workers. Vitamin D3 5000 IU supplementation was associated with a lower risk of ILI (incidence rate difference: -1.7 × 10 -4 /person-day, 95%-CI: -3.0 × 10 -4 to -3.3 × 10 -5 /person-day, p = 0.015) and a lower incidence rate for non-COVID-19 ILI (incidence rate difference: -1.3 × 10 -4 /person-day, 95%-CI -2.5 × 10 -4 to -7.1 × 10 -6 /person-day, p = 0.038). COVID-19 ILI incidence was not statistically different (incidence rate difference: -4.2 × 10 -5 /person-day, 95%-CI: -10.0 × 10 -5 to 1.5 × 10 -5 /person-day, p = 0.152). Daily supplementation with 5000 IU vitamin D3 reduces influenza-like illness in healthcare workers.

Tonsil complaints in adults are common. If conservative treatment fails, there is an indication for surgical removal of the tonsils. The current standard procedure, tonsillectomy under anaesthesia, is invasive, painful, and relatively often leads to complications including postoperative bleeding. There is an alternative procedure: the CO2 laser tonsillotomy under local anaesthesia. In this procedure, only the lymphatic tissue is removed. As a result, this procedure is associated with significantly less pain, shorter recovery, less postoperative bleeding, and a significant reduction in tonsil complaints.

Introduction Acute kidney injury (AKI) remains a serious complication after surgery with cardiopulmonary bypass (CPB). A relationship similar to the one between coronary artery calcification and increased incidence of cardiac complications is hypothesized to exist for aortic calcification and the development of AKI. Elevated pulse pressure (PP) hypertension has been shown to be a predictor of AKI-CPB (AKI after CPB surgery), and calcium deposition and stiffening of the body's conduit arteries may be part of this process. We hypothesized that calcium scores obtained from non-contrast computed tomography (CT) scans of the infrarenal aorta and renal arteries would be independently and significantly associated with AKI-CPB. Methods We conducted a retrospective study of 65 subjects who underwent non-emergent open heart surgery with CPB in a tertiary healthcare center. AKI-CPB was diagnosed using the Acute Kidney Injury Network criteria. Aortic and renal artery calcium (Agatston) scores were obtained and entered into a multivariable logistic regression model alongside other significant predictors of AKI-CPB from a univariable analysis. Results Pulse pressure, body surface area, and pre-operative serum creatinine were significantly associated with the development of AKI-CPB, but the calcium scores were not. For PP, the odds ratio (OR) was 1.062, (95% Wald confidence interval {CI}=1.012 - 1.114). The OR for the calcium score in the aorta was 1.0000 (95% CI=1.0 - 1.0). Conclusions Agatston calcium scores in the renal arteries and infrarenal aorta were not independently associated with AKI-CPB, but arterial stiffening, as indicated by elevated pulse pressure, was predictive of AKI-CPB., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Mitrev et al.)

Objective: To investigate if oxygen delivery index during cardiopulmonary bypass (DO 2 I) was more strongly associated with acute kidney injury (AKI), the higher the patient's preoperative pulse pressure (PP)., Design: Retrospective cohort of 1064 patients undergoing cardiac surgery., Setting: Single academic healthcare center., Participants: Adult patients undergoing coronary artery bypass grafting, valve, aortic, or combined surgery requiring cardiopulmonary bypass., Interventions: Hemoglobin, arterial oxygen saturation, and pump flow recorded no fewer than every 30 min were extracted from the patients' perfusion records, and DO 2 I was calculated. The AKI was assessed from the pre- and postoperative creatinine and urine output values using the Acute Kidney Injury Network criteria. The sample was stratified in 5 categories of progressively higher PP. The patient characteristics and intraoperative variables were evaluated in univariate analysis for a relationship with AKI. The significant risk factors from the univariate analysis then were evaluated in a multivariate analysis and assessed for logistic fit with respect to AKI., Primary Outcome: The AKI assessed as a binary outcome., Measurements and Main Results: Age, body surface area, DO 2 I, history of heart failure, and baseline creatinine were associated significantly with AKI, as was an interaction term between the PP category and DO 2 I (p = 0.0067). The higher the PP category, the stronger the observed association between DO 2 I and AKI, and the higher the variability in the predicted risk of AKI dependent on DO 2 I., Conclusions: A lower DO 2 I during cardiopulmonary bypass appeared more strongly associated with a higher likelihood of developing AKI, the higher the patient's preoperative pulse pressure., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Dorsal root ganglion stimulation (DRG-S) is a form of neuromodulation used to treat chronic pain. A spinal cord stimulation (SCS) method with paresthesia-free waveform used in the dorsal columns, burst-SCS, recently demonstrated efficacy using intermittent stimulation, where stimulation is cycled on and off for set durations. Tonic SCS is a paresthesia-based therapy that is ineffective at sub-perception levels and when delivered in a cycled manner. DRG-S also uses a tonic waveform, yet unlike tonic SCS, it is effective at sub-perception levels. This study aimed to determine whether the cycling of stimulation at the DRG could maintain DRG-S efficacy., Materials and Methods: This study followed a prospective, randomized, and balanced, double-blinded (assessor) protocol. Twenty DRG-S responders were randomized to a sequence of three programs for consecutive two-week intervals: continuous stimulation; 1 minute on:1 minute off; or 1 minute on:2 minutes off. The primary outcome of this study was change in pain ratings with the cycled programs compared with continuous stimulation. Secondary outcomes included changes in function and scores for quality of life, and stimulation program preference., Results: Mean scores were similar at the end of each two-week stimulation program for Numerical Rating Scale pain (continuous = 2.9 ± 0.8, 1:1 on-off = 2.6 ± 0.7, and 1:2 on-off = 2.7 ± 0.7 cm, p = 0.39), disability (p = 0.72), and general health (p = 0.95). No clinically significant differences were found from the upper boundaries of the 95% confidence intervals of the mean difference in pain, disability, and general health for each intermittent stimulation program vs the continuous program. At the end of the study, the continuous stimulation, 1:1 on-off dosing, and 1:2 on-off dosing programs were preferred by a similar number of patients., Conclusions: Intermittent DRG-S produces comparable results to continuous stimulation over a two-week period. Intermittent delivery may extend battery life and facilitate a smaller implantable pulse generator., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Spinal cord stimulation (SCS) can provide long-term pain relief for various chronic pain conditions, but some patients have no relief with trial stimulation or lose efficacy over time. To "salvage" relief in patients who do not respond or have lost efficacy, alternative stimulation paradigms or anatomical targets can be considered. Dorsal root ganglion stimulation (DRG-S) has a different mechanism of action and anatomical target than SCS., Objectives: We assessed DRG-S salvage therapy outcomes in patients who did not respond to SCS or had lost SCS efficacy., Materials and Methods: We retrospectively included consecutive patients from 2016 to 2020 who were salvaged with DRG-S after failed SCS trials (<50% pain reduction) or who had lost efficacy after permanent SCS. We compared numerical rating scale (NRS) pain, Oswestry disability index (ODI), health-related quality of life (EuroQol five-dimensions five-level), and oral morphine equivalent (OME) opioid requirements before DRG-S salvage and at patients' last follow-up., Results: A total of 60 patients who had failed SCS were salvaged with DRG-S. The mean age was 56 ± 12 years, and the most common diagnoses were complex regional pain syndrome (n = 24) and failed back surgery syndrome (n = 24). The most common failed modalities included tonic (n = 32), Burst (n = 18), and high-frequency (n = 10) SCS. The median follow-up duration of salvage DRG-S was 34 months. With DRG-S, NRS decreased (8.7 ± 1.2 to 3.8 ± 2.1), and OME declined (median 23 mg to median 15 mg), whereas EuroQol 5D scores increased (0.40 ± 0.15 to 0.71 ± 0.15), and ODI improved (64 ± 14% to 31 ± 18%) (all p < 0.05)., Conclusions: DRG-S can be used in patients with chronic pain who have previously failed to receive persistent benefit from SCS., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: A heightened and organized understanding of sacral anatomy could potentially lead to a more effective and safe method of dorsal root ganglion stimulation (DRG-S) lead placement. The aim of this technical note is to describe a standardized access method for S1 DRG-S lead placement., Design: Technical note., Methods: The described approach utilizes alignment of the lumbosacral prominence and is measurement-based, allowing for standardized sacral access, even when visualization is suboptimal. The medial-to-lateral needle trajectory is designed to limit interaction with the sensitive neural structures and allows for a more parallel orientation of the lead to the DRG and nerve root., Conclusions: The described technique potentially improves the safety of S1 DRG-S lead placement. The parallel lead orientation to the DRG may also increase efficacy while lowering energy requirements., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Introduction: Dorsal root ganglion stimulation (DRG-S) is a relatively new neuromodulation modality. Therefore, data on long-term device explantation rates is limited. This investigation aimed to assess DRG-S device explantation rates at long-term follow-up., Methods: We retrospectively reviewed individuals implanted with DRG-S in four pain centers from different continuous periods between April 2016 to September 2020. We recorded patient demographics, diagnoses, duration to explantation or last follow-up, treatment complications, and failure etiologies., Results: A total of 249 patients with 756 leads and a mean 27-month follow-up were included. The mean age was 55 ± 15 years; 148 (63%) were female. Leading diagnoses were CRPS (n = 106, 43%), followed by FBSS (n = 64, 26%), and non-surgical low back pain (n = 23, 9%). The explantation rate was ~2% per year (n = 10 total). At explantation, the average time from implantation was 13 ± 10 months. Six patients were explanted for inadequate pain relief. Two patients were explanted due to device-related complications. One patient was explanted secondary to infection and subsequently reimplanted. Five explanted patients experienced a therapy-related complication before eventual explantation: one transient post-procedural neuritis and pocket site pain, one lead fracture, two lead migrations, and one experienced a fracture, a migration, and pocket site pain., Discussion: This large retrospective study of DRG-S revealed a low therapy-termination rate. The rate of infection leading to explantation was objectively very low at 0.4%. The leading cause of explantation was inadequate pain relief. Explanted patients often had a therapy-related complication. Therefore, minimizing adverse treatment events may reduce ultimate explantation rates., (© 2022 World Institute of Pain.)

Background: Electrolyte administration during massive transfusion without readily available calcium laboratory values is likely ubiquitous but not well standardized. We aimed to quantify the incidence, degree, and timing of hypocalcemia during the first 24 hours after initiation of a massive transfusion with the institutional massive transfusion protocol (MTP). We hypothesized that hypocalcemia is prevalent during acute resuscitation (first six hours) despite efforts of the treatment team to replete calcium during active resuscitation., Methods: A retrospective chart review of all patients who underwent MTP at our institution between January 1, 2017, and December 31, 2017, was performed. The primary outcome was hypocalcemia from a massive transfusion during the first six hours after the initiation of the MTP. Secondary outcomes of interest included hypercalcemia, hypomagnesemia, hospital mortality, peak and nadir timing of hypocalcemia and hypercalcemia, calcium supplementation, and calcium supplementation timing. Calcium administration and blood product transfusion is reported relative to the start of the MTP. The association between the total amount of calcium administered and the total number of blood products transfused was assessed., Results: Data from 52 massive transfusions were analyzed. Ninety-seven percent of patients were hypocalcemic during the first six hours of resuscitation. The nadir occurred after median of eight units of blood product were given, (interquartile range {IQR}: 4-16). Calcium supplementation correlated with the total number of blood products transfused (ρ = 0.47, p < 0.01). Patients in whom calcium was supplemented received more blood products when compared to patients in whom calcium was not supplemented (median: 16, IQR: 12-26 vs. median: 9, IQR: 7-12, p <0.01)., Conclusions: Hypocalcemia from massive transfusion is common. The incidence of hypocalcemia in MTP has been reported to be 85-97%. Calcium supplementation that is not standardized in MTP may lead to underutilization during massive transfusion and to hypocalcemia in these patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Potestio et al.)

Importance: Carbon dioxide laser tonsillotomy performed under local anesthesia may be an effective and less invasive alternative than dissection tonsillectomy for treatment of tonsil-related afflictions., Objective: To compare functional recovery and symptom relief among adults undergoing tonsillectomy or tonsillotomy., Design, Setting, and Participants: This randomized clinical trial was conducted at 5 secondary and tertiary hospitals in the Netherlands from January 2018 to December 2019. Participants were 199 adult patients with an indication for surgical tonsil removal randomly assigned to either the tonsillectomy or tonsillotomy group., Interventions: For tonsillotomy, the crypts of the palatine tonsil were evaporated using a carbon dioxide laser under local anesthesia, whereas tonsillectomy consisted of total tonsil removal performed under general anesthesia., Main Outcomes and Measures: The primary outcome was time to functional recovery measured within 2 weeks after surgery assessed for a modified intention-to-treat population. Secondary outcomes were time to return to work after surgery, resolution of primary symptoms, severity of remaining symptoms, surgical complications, postoperative pain and analgesics use, and overall patient satisfaction assessed for the intention-to-treat population., Results: Of 199 patients (139 [70%] female; mean [SD] age, 29 [9] years), 98 were randomly assigned to tonsillotomy and 101 were randomly assigned to tonsillectomy. Recovery within 2 weeks after surgery was significantly shorter after tonsillotomy than after tonsillectomy (hazard ratio for recovery after tonsillectomy vs tonsillotomy, 0.3; 95% CI, 0.2-0.5). Two weeks after surgery, 72 (77%) patients in the tonsillotomy group were fully recovered compared with 26 (57%) patients in the tonsillectomy group. Time until return to work within 2 weeks was also shorter after tonsillotomy (median [IQR], 4.5 [3.0-7.0] days vs 12.0 [9.0-14.0] days; hazard ratio for return after tonsillectomy vs tonsillotomy, 0.3; 95% CI, 0.2-0.4.). Postoperative hemorrhage occurred in 2 patients (2%) in the tonsillotomy group and 8 patients (12%) in the tonsillectomy group. At 6 months after surgery, fewer patients in the tonsillectomy group (25; 35%) than in the tonsillotomy group (54; 57%) experienced persistent symptoms (difference of 22%; 95% CI, 7%-37%). Most patients with persistent symptoms in both the tonsillotomy (32 of 54; 59%) and tonsillectomy (16 of 25; 64%) groups reported mild symptoms 6 months after surgery., Conclusions and Relevance: This randomized clinical trial found that compared with tonsillectomy performed under general anesthesia, laser tonsillotomy performed under local anesthesia had a significantly shorter and less painful recovery period. A higher percentage of patients had persistent symptoms after tonsillotomy, although the intensity of these symptoms was lower than before surgery. These results suggest that laser tonsillotomy performed under local anesthesia may be a feasible alternative to conventional tonsillectomy in this population., Trial Registration: Netherlands Trial Register Identifier: NL6866 (NTR7044).

Convalescent plasma is used to treat COVID-19. There are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade particularly among patients with severe COVID-19. The aim of this study was to evaluate the coagulation profile of COVID-19 convalescent plasma. Clotting times and coagulation factor assays were compared between fresh frozen plasma, COVID-19 convalescent plasma, and pathogen-reduced COVID-19 convalescent plasma. Measurements included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer, von Willebrand factor activity, von Willebrand factor antigen, coagulation factors II, V, VII-XII, protein S activity, protein C antigen, and alpha-2 plasmin inhibitor. Clotting times and coagulation factor assays were not different between COVID-19 convalescent plasma and fresh frozen plasma, except for protein C antigen. When compared to fresh frozen plasma and regular convalescent plasma, pathogen reduction treatment increased activated partial thromboplastin time and thrombin time, while reducing fibrinogen, coagulation factor II, V, VIII, IX, X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor. The coagulation profiles of human COVID-19 convalescent plasma and standard fresh frozen plasma are not different. Pathogen reduced COVID-19 convalescent plasma is associated with reduction of coagulation factors and a slight prolongation of coagulation times, as anticipated. A key limitation of the study is that the COVID-19 disease course of the convalesced donors was not characterized., (© 2022. The Author(s).)

Background: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma., Methods and Findings: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects., Conclusions: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease., Trial Registration: ClinicalTrials.gov NCT#: NCT04338360., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Dorsal root ganglion stimulation (DRG-S), has demonstrated superiority in the treatment of complex regional pain syndrome and causalgia. Lead migration and fracture impact DRG-S therapeutic stability. Lead anchoring reduces DRG-S lead migration without increasing lead fracture. Lead fracture may be related to lead entrapment in the superficial fascial plane. A novel medialized approach for lead placement and anchoring is presented to address these issues., Methods: We suggest an alternative technique for implanting percutaneous DRG-S leads at the T10-L5 levels., Results: A novel medialized ipsilateral technique for lead placement and anchoring for single, bilateral, and adjacent segment placement is presented. The Tuohy needle puncture site is medial to the pedicle and adjacent to the spinous process, two vertebral levels caudad to the target foramen. Trajectory is maintained in the sagittal plane, to access the caudad interlaminar space near the midline. This technique allows for ipsilateral or contralateral lead placement. After epidural access, the introducer sheath is rotated toward the targeted foramen and advanced. The guidewire followed by the lead is passed, and once lead position is confirmed, tension "S" loops are created, followed by anchoring to the deep fascia., Conclusion: We describe a new paramedian technique for DRG-S lead placement. We propose it will decrease DRG-S complication rates through anchoring to reduce migration and by avoiding the fascial planes thought to be responsible for fracture. Long-term outcomes applying our proposed techniques are required for determining the true impact, however, early anecdotal results suggest that these new techniques are favorable., (© 2021 World Institute of Pain.)

Introduction: Dorsal root ganglion stimulation (DRG-S) is a neuromodulation technique introduced in the last decade with evolving implant methods. Initial prospective research found low incidences of lead migration and lead fracture with DRG-S. However, several recent studies have highlighted high lead migration and lead fracture rates with DRG-S. We investigated the influence of lead anchoring on migrations and fractures., Methods: We performed a retrospective review between 2016 and 2020 of individuals implanted with DRG-S leads by 4 experienced implanters. The implanters independently changed their standard practice regarding lead anchoring over time, with opposing trends (no anchoring > anchoring, anchoring > no anchoring). We compared lead migration and lead fracture rates between anchored and unanchored DRG-S leads in the entire study cohort. Cox regression was performed on lead migration and fracture distributions., Results: We included 756 leads (n = 565 anchored and n = 191 unanchored) from 249 patients. In unanchored leads, migration occurred in 16 leads (8.4%) from 13 patients (21.0%). In anchored leads, migration occurred in 8 leads (1.4%) from 5 patients (2.7%). Fracture in unanchored leads occurred in 6 leads (3.1%) from 6 patients (9.7%). Fractures in anchored leads occurred in 11 leads (1.9%) from 9 patients (4.8%). The migration survival distributions for the anchored and unanchored leads were statistically significantly different (p < 0.01) with decreased survival for unanchored leads (hazard ratio = 5.8, 95% confidence interval [CI] = 2.2-15.5)., Discussion: We found that anchoring DRG-S leads significantly reduces lead migration when compared to leads placed without an anchor. There was no significant difference in fracture rate between anchored and unanchored leads., (© 2021 World Institute of Pain.)

Introduction It is valuable to know if country demographic, educational, healthcare and other socioeconomic factors were correlated with the COVID-19 mortality rate during the initial phase of the coronavirus disease 2019 (COVID-19) worldwide pandemic (January 1 st  - August 31 st , 2020). Similarly, it is worthwhile understanding whether a country's geographic location or the measures instituted by governments, such as lockdowns and mask-wearing, were associated with an increased or decreased mortality rate. Materials and methods To assess these correlations, we conducted an ecologic study of 178 countries using time-matched data from the Social Progress Index (www.socialprogress.org, produced by the Social Progress Imperative), population data from the World Bank (data.worldbank.org), government response indices from Our World In Data (ourworldindata.org/policy-responses-covid), and COVID-19 mortality data from the Johns Hopkins University CSSE COVID-19 Data repository (github.com/CSSEGISandData/COVID-19), accessed on November 22 nd , 2020. Pearson correlation coefficients were derived between potential predictors and countries' COVID-19 population-adjusted crude mortality rates. Select variables were entered in a multivariable regression model. Countries with no data in the social progress index database or those with no COVID-19 cases were excluded (20 in total).  Results The highest positive correlations were found between the proportion of the population older than 75 (Pearson correlation coefficient 0.321), country distance from the equator (0.267), gross domestic product per capita (0.218), health and wellness score (0.388), water and sanitation score (0.384), environmental quality (0.237), and the days between the first reported COVID-19 case and the initial government response (0.238). A previously unreported and unexpected negative correlation was found between gender parity in secondary education attainment and COVID-19 mortality (-0.290). Peak mask-wearing ranging from 'recommended' to 'required outside the home at all times was extremely weakly correlated with lower COVID-19 mortality (-0.046). Conclusions Crude COVID-19 mortality rates during the first phase of the pandemic in 2020, during which no vaccine or specific treatment was available, were higher in wealthier countries that were further away from the equator and had a higher health and wellness score according to the Social Progress Imperative. They were also higher the longer governments delayed their initial response. Gender parity in secondary education and stringency of mask-wearing guidelines were correlated with lower mortality, though the latter correlation was extremely weak. Our findings are consistent with previously published correlations. The correlation between crude COVID-19 mortality rates and gender parity in secondary education has not been previously reported., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Mitrev et al.)

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge., (© 2021. The Author(s).)

Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but limited or no benefit later in the disease course when patients required greater supportive therapies. RCTs have also revealed that convalescent plasma transfusion contributes to improved symptomatology and viral clearance. To further investigate the effect of convalescent plasma on patient mortality, we performed a meta-analytical approach to pool daily survival data from all controlled studies that reported Kaplan-Meier survival plots. Qualitative inspection of all available Kaplan-Meier survival data and an aggregate Kaplan-Meier survival plot revealed a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy, whereby convalescent plasma transfusion was generally associated with greater patient survival. Given that convalescent plasma has a similar safety profile as standard plasma, convalescent plasma should be implemented within weeks of the onset of future infectious disease outbreaks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Klassen, Senefeld, Senese, Johnson, Wiggins, Baker, van Helmond, Bruno, Pirofski, Shoham, Grossman, Henderson, Wright, Fairweather, Paneth, Carter, Casadevall and Joyner.)

Background: Dorsal root ganglion stimulation (DRG-S) is a novel approach to treat chronic pain. Lead placement at L2 has been reported to be an effective treatment for axial low back pain (LBP) primarily of discogenic etiology. We have recently shown, in a diverse cohort including cases of multilevel instrumentation following extensive prior back surgeries, that DRG-S lead placement at T12 is another promising target. Local effects at the T12 DRG, alone, are insufficient to explain these results., Materials and Methods: We performed a literature review to explore the mechanisms of LBP relief with T12 DRG-S., Findings: Branches of individual spinal nerve roots innervate facet joints and posterior spinal structures, while the discs and anterior vertebrae are carried via L2, and converge in the dorsal horn (DH) of the spinal cord at T8-T9. The T12 nerve root contains cutaneous afferents from the low back and enters the DH of the spinal cord at T10. Low back Aδ and C-fibers then ascend via Lissauer's tract (LT) to T8-T9, converging with other low back afferents. DRG-S at T12, then, results in inhibition of the converged low back fibers via endorphin-mediated and GABAergic frequency-dependent mechanisms. Therefore, T12 lead placement may be the optimal location for DRG-S to treat LBP., (© 2020 International Neuromodulation Society.)

Background: Dorsal root ganglion stimulation (DRG-S) involves the electrical modulation of the somata of afferent neural fibers to treat chronic pain. DRG-S has demonstrated clinical efficacy at frequencies lower than typically used with spinal cord stimulation (SCS). In a clinical study, we found that the frequency of DRG-S can be tapered to a frequency as low as 4 Hz with no loss of efficacy. This review discusses possible mechanisms of action underlying effective pain relief with very low-frequency DRG-S., Materials and Methods: We performed a literature review to explore the role of frequency in neural transmission and the corresponding relevance of frequency settings with neuromodulation., Findings: Sensory neural transmission is a frequency-modulated system, with signal frequency determining which mechanisms are activated in the dorsal horn. In the dorsal horn, low-frequency signaling (<20 Hz) activates inhibitory processes while higher frequencies (>25 Hz) are excitatory. Physiologically, low-threshold mechanoreceptors (LTMRs) fibers transmit or modulate innocuous mechanical touch at frequencies as low as 0.5-5 Hz, while nociceptive fibers transmit pain at high frequencies. We postulate that very low-frequency DRG-S, at least partially, harnesses LTMRs and the native endogenous opioid system. Utilizing lower stimulation frequency decreases the total energy delivery used for DRG-S, extends battery life, and facilitates the development of devices with smaller generators., (© 2020 International Neuromodulation Society.)