Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19.

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.).

Evaluation of Washout Periods After Dorsal Root Ganglion Stimulation Trial.

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.

Lead migration rate in dorsal root ganglion stimulation using lead anchoring techniques: A follow-up study.

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.

Dorsal root ganglion stimulation for the treatment of joint pain with predominantly nociceptive characteristics: A case series.

INTRODUCTION: Dorsal root ganglion stimulation (DRG-S) has recently emerged as a novel therapy in neuromodulation that demonstrated a higher rate of success than spinal cord stimulation (SCS) in a prospective, head-to-head randomized comparative trial to treat complex regional pain syndrome (CRPS) and causalgia. In contrast to SCS, DRG-S also shows promise in treating conditions that are not purely neuropathic such as axial low back pain, which has a prominent nociplastic pain component. It is not known to what extent the effectiveness of DRG-S for such indications is due to effective treatment of the neuropathic pain component versus the effects of DRG-S on mechanical pain. Although rarely studied, reporting outcomes of DRG-S to treat predominantly mechanical/nociceptive pain may help point toward expanding the utility of this therapy. Here, we present five cases of refractory mechanical pain treated with DRG-S. METHODS: A retrospective analysis of all patients who underwent a successful DRG-S trial and implant between September 2017 and September 2021 at our institute was performed. Patients who had intractable joint pain without strong evidence of neuropathic pain were included in this case series. The Budapest criteria for CRPS, the Douleur Neuropathique 4 Questions (DN4) survey, or a definable nerve injury were used to determine the presence of neuropathic pain. Baseline assessments for pain (Numeric Rating Scale [NRS]), function (Oswestry Disability Index [ODI]), quality of life (EuroQol-5 Dimension [EQ-5D]), and other applicable joint surveys were extracted from pre-trial baseline and follow-up appointments. RESULTS: Five patients were identified and included. Patient diagnoses consisted of refractory joint pain of the hip, knee, or ankle. Mean NRS pain scores improved by 74% from 9.2 at baseline to 2.4 at the last follow-up (mean = 28 months post-implant). From baseline to the last follow-up, mean ODI scores improved by 65% from 66 to 23 and EQ-5D scores more than doubled from an average of 0.371 to 0.797. CONCLUSION: This clinical report illustrates the potential utility DRG-S has in treating pain that clinically presents as predominantly refractory mechanical joint pain without a significant neuropathic component. The physiological reasons for our observations may be that DRG-S is able to directly influence the conduction of nociceptive signaling at the DRG and within the spinal cord. Further investigations are warranted to determine if DRG-S is a potential treatment option for chronic mechanical pain.

An Anatomy-Informed, Novel Technique for S1 Dorsal Root Ganglion Stimulation Lead Placement.

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.

Association of Preoperative Pulse Pressure and Oxygen Delivery Index During Cardiopulmonary Bypass With Postoperative Acute Kidney Injury.

OBJECTIVE: To investigate if oxygen delivery index during cardiopulmonary bypass (DO2I) 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 DO2I 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, DO2I, history of heart failure, and baseline creatinine were associated significantly with AKI, as was an interaction term between the PP category and DO2I (p = 0.0067). The higher the PP category, the stronger the observed association between DO2I and AKI, and the higher the variability in the predicted risk of AKI dependent on DO2I. CONCLUSIONS: A lower DO2I during cardiopulmonary bypass appeared more strongly associated with a higher likelihood of developing AKI, the higher the patient's preoperative pulse pressure.

Intermittent Dorsal Root Ganglion Stimulation Is as Efficacious as Standard Continuous Dosing in Treating Chronic Pain: Results From a Randomized Controlled Feasibility Trial.

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.

Dorsal Root Ganglion Stimulation as a Salvage Therapy Following Failed Spinal Cord Stimulation.

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.

Dorsal root ganglion stimulation device explantation: A multicenter pooled data analysis.

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.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

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.

Objective Improvements in Peripheral Arterial Disease from Dorsal Root Ganglion Stimulation: A Case Series.

BACKGROUND: The sympathetic nervous system (SNS) is important in the regulation of perfusion. Dorsal root ganglion stimulation (DRG-S) modulates sympathetic tone and is approved to treat complex regional pain syndrome, a disorder related to SNS dysfunction. We herein present 3 cases of DRG-S therapy to improve blood flow and symptoms of ischemia in peripheral arterial disease (PAD). METHODS: Patient 1 is a 44-year-old female with dry gangrene of the third and fourth digits of her right hand due to Raynaud's syndrome who was scheduled for amputation of the affected digits. DRG-S leads were placed at the right C6, 7, and 8 DRG. Pulse volume recordings (PVR) were measured at baseline and after DRG-S. Patient 2 is a 55-year-old female with a non-healing ulcer of her left foot secondary to PAD scheduled for a below the knee amputation who underwent a DRG-S trial with leads placed at the left L4 and L5 DRG followed by a spinal cord stimulation trial with leads placed at the T9-T10 spinal levels for comparison. Transcutaneous oximetry (TcPO2) was measured at baseline and after 3 days of each therapy. Patient 3 is a 69-year-old female with persistent left foot pain at rest secondary to PAD with DRG-S leads placed at the left L4 and S1 levels. RESULTS: All 3 patients experienced a significant reduction in pain with DRG-S, along with improvements in blood flow of the involved extremities, avoiding or limiting amputation. PVR improved dramatically with DRG-S in patient 1. A greater improvement in TcPO2 was seen with the DRG-S trial compared to spinal cord stimulation trial in patient 2. Patient 3 experienced an increase in walking distance and demonstrated long term efficacy and limb salvage at 32 months postimplantation. CONCLUSIONS: Modulation of SNS output from DRG-S through orthodromic and antidromic autonomic pathways is likely responsible for improving blood flow. DRG-S may be a treatment option for PAD.

The Pathways and Processes Underlying Spinal Transmission of Low Back Pain: Observations From Dorsal Root Ganglion Stimulation Treatment.

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.

Very Low Frequencies Maintain Pain Relief From Dorsal Root Ganglion Stimulation: An Evaluation of Dorsal Root Ganglion Neurostimulation Frequency Tapering.

BACKGROUND: Dorsal root ganglion neurostimulation (DRG-S) is effective in treating various refractory chronic pain syndromes. In preclinical studies, DRG-S at very low frequencies (<5 Hz) reduces excitatory output in the superficial dorsal horn. Clinically, we have also observed the effectiveness of DRG-S at low frequencies. We conducted a case series to describe the effect of very low-frequency DRG-S stimulation on clinical outcomes. MATERIALS AND METHODS: DRG-S for refractory low back pain was initiated at parameters consistent with published values. Thereafter, the stimulation frequency of DRG-S was reduced in a stepwise fashion to the lowest frequency that maintained pain relief. Pain intensity, disability, and general health status data were collected at baseline, prior to initiation of tapering, and at four weeks after each patient's lowest effective stimulation frequency was reached. RESULTS: After device activation (N = 20), DRG-S frequency was tapered from 16 to 4 Hz over a 4- to 17-week period, reducing charge-per-second by nearly two-thirds. Even so, pain relief was maintained at more than 75%, with consistent findings in the other measures. CONCLUSION: DRG-S may have utility in treating chronic pain at lower stimulation frequencies than previously recognized. We have previously theorized that the mechanism of action may involve preferential recruitment of low-threshold mechanoreceptor fibers via the endogenous opioid system. Of clinical relevance, lower frequency stimulation maintains DRG-S efficacy regarding improvements in pain, disability, and quality of life. It can extend battery life and may potentially lead to the development of smaller implantable pulse generators.

Mechanisms for the Clinical Utility of Low-Frequency Stimulation in Neuromodulation of the Dorsal Root Ganglion.

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.

Convalescent Plasma for Infectious Diseases: Historical Framework and Use in COVID-19.

Convalescent plasma has emerged as a promising therapeutic agent for patients with coronavirus disease 2019 (COVID-19), has received emergency use authorization, and is being widely used during the COVID-19 pandemic. Passive antibody therapy via plasma or serum has been successfully used to treat infectious diseases for more than a century. Passive antibody administration is based on the presumption that convalescent plasma or serum contains therapeutic antibodies that can be passively transferred to the plasma recipient. There are numerous examples in which convalescent plasma has been used successfully as post-exposure prophylaxis and treatment of infectious diseases, including previous coronavirus outbreaks. In the context of the COVID-19 pandemic, convalescent plasma was demonstrated to be safe and potentially effective among patients infected with COVID-19. This review provides an overview of the historical uses of convalescent plasma therapy, summarizes current evidence for convalescent plasma use for COVID-19, and highlights future antibody therapies.

Dorsal Root Ganglion Stimulation Normalizes Measures of Pain Processing in Patients with Chronic Low-Back Pain: A Prospective Pilot Study using Quantitative Sensory Testing.

BACKGROUND: Dorsal root ganglion stimulation (DRG-S) is used as a treatment for chronic low-back pain (CLBP), although its underlying mechanisms remain elusive. CLBP patients have been found to have reduced mechanoreceptive perception, reduced endogenous analgesia, as well as deep-tissue hyperalgesia when compared with healthy controls. Using quantitative sensory testing (QST), we studied if DRG-S in CLBP patients results in changes in pain processing. METHODS: Quantitative sensory testing was performed in patients before trial implantation of a DRG-S system for CLBP and just before the trial lead removal or at 1-month follow-up after the permanent implant. We determined the pressure pain threshold (PPT) and mechanical detection threshold (MDT) at the most painful lower-back location. PPT was also measured on the contralateral shoulder as a control. We obtained a measure of endogenous inhibitory pain modulation using conditioned pain modulation (CPM). RESULTS: We enrolled 11 patients (60 ± 16 years). Pain decreased from 8.5 ± 1.0 at baseline to 2.0 ± 1.5 on a 0-10 numerical rating scale with DRG-S (P < 0.01). From baseline to with DRG-S, PPT on the most painful location on the low back increased from 28.7 ± 13.6 to 43.4 ± 17.2 N/cm2 (P < 0.01). MDT on the same location decreased from 8.1 ± 10.4 to 3.4 ± 4.7 mN (P = 0.07). PPT on the control location and CPM did not change significantly. CONCLUSIONS: Our results suggest that DRG-S in CLBP patients reduces deep-tissue hyperalgesia in the low back, while improving mechanoreceptive perception. These changes in both neuropathic and nociceptive components of CLBP were accompanied by clinical improvements in pain and function.

A paramedian approach for dorsal root ganglion stimulation placement developed to limit lead migration and fracture.

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.

Lead migration and fracture rate in dorsal root ganglion stimulation using anchoring and non-anchoring techniques: A multicenter pooled data analysis.

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.

Is Preoperative Quantitative Sensory Testing Related to Persistent Postsurgical Pain? A Systematic Literature Review.

Persistent postsurgical pain (PPSP) is a common complication of surgery that significantly affects quality of life. A better understanding of which patients are likely to develop PPSP would help to identify when perioperative and postoperative pain management may require specific attention. Quantitative sensory testing (QST) of a patient's preoperative pain perception is associated with acute postoperative pain, and acute postoperative pain is a risk factor for PPSP. The direct association between preoperative QST and PPSP has not been reviewed to date. In this systematic review, we assessed the relationship of preoperative QST to PPSP. We searched databases with components related to (1) preoperative QST; (2) association testing; and (3) PPSP. Two authors reviewed all titles and abstracts for inclusion. Inclusion criteria were as follows: (1) QST performed before surgery; (2) PPSP assessed ≥3 months postoperatively; and (3) the association between QST measures and PPSP is investigated. The search retrieved 905 articles; 24 studies with 2732 subjects met inclusion criteria. Most studies (22/24) had moderate to high risk of bias in multiple quality domains. Fourteen (58%) studies reported a significant association between preoperative QST and PPSP. Preoperative temporal summation of pain (4 studies), conditioned pain modulation (3 studies), and pressure pain threshold (3 studies) showed the most frequent association with PPSP. The strength of the association between preoperative QST and PPSP varied from weak to strong. Preoperative QST is variably associated with PPSP. Measurements related to central processing of pain may be most consistently associated with PPSP.

T12 Dorsal Root Ganglion Stimulation to Treat Chronic Low Back Pain: A Case Series.

INTRODUCTION: Dorsal root ganglion stimulation (DRG-S) is a neuromodulation technique for treating neuropathic pain syndromes. Research has demonstrated DRG-S to be more effective than conventional SCS in treating RSD/CRPS, particularly of the lower extremities. Results from recent case series and prospective studies suggest that DRG-S may be effective in treatment of pain syndromes considered to have non-neuropathic components and characteristics (e.g. nociceptive). There have been multiple, small studies demonstrating efficacy of DRG-S for axial low back pain. There has, however, been no consensus regarding the best location for DRG lead placement in the treatment of low back pain. METHODS: Patients presenting with refractory low back pain in a private pain management practice were considered for DRG-S. Patients were provided a trial stimulator prior to potential implantation. Per standard practice, pain intensity, disability, general health status, and quality of life were followed using the visual analog scale (VAS), Oswestry Disability Index, EQ-5D index, and the SF-36 survey, respectively. Data were collected prior to implantation and at variable follow-ups after DRG-S initiation. RESULTS: Seventeen consecutive patients presented with predominantly axial low back pain with/without a secondary component of lower extremity pain. All were trialed and subsequently implanted for DRG-S. Leads were placed at T12 to target the low back. Stimulation levels were set very low, below that of which patients experienced paresthesias. Last follow-up times averaged 8.3 months. More than half of the patients experienced pain relief ≥80%, with an average low back pain relief of 78% at last follow-up. Additionally, substantial improvements in physical and mental functioning, disability, and quality of life were reported. CONCLUSIONS: T12 DRG-S can be an effective treatment for chronic axial low back pain. Stimulation results in reduced pain and disability, while improving quality of life. These outcomes can be achieved without paresthesias.