Faculty Bibliography

BACKGROUND/UNASSIGNED:Pain chronicization is commonly used to describe the transition from acute to chronic pain driven by central mechanisms. OBJECTIVE/UNASSIGNED:To reassess its clinical relevance by comparing neurobiological models with patient observation. METHODS/UNASSIGNED:Conceptual analysis integrating experimental data and clinical experience. The analysis particularly considers animal models, human neuroimaging and ICD‑11 chronic pain categories. RESULTS/UNASSIGNED:While central sensitization is well established experimentally, clinical observation rarely shows a clear transition from acute to chronic pain. Chronic pain is typically heterogeneous, discontinuous and influenced by multiple factors. Neuroimaging findings are largely associative and lack temporal and causal definition. The distinction between chronic primary and secondary pain is clinically useful but does not demonstrate a biological conversion. CONCLUSION/UNASSIGNED:Pain chronicization should be considered a theoretical construct rather than a clinically demonstrable process, and interpreted with caution in individual patients.

As interest in donation after circulatory death for heart transplantation (DCD-HT) grows, the need to standardize protocols and address ongoing controversies becomes increasingly apparent. However, efforts toward standardization are complicated by the fact that numerous organ procurement organizations, transplant centers, and academic societies have each posited their own protocols. While some degree of variability is inevitable and sometimes necessary, variability regarding end-of-life care, definitions for reported metrics, and standards for allograft assessment may lead to inefficiencies in scaled execution and worsen ethical controversies for donors at the end of life. This review analyzes key areas of variation in contemporary DCD-HT protocols, including donor selection, management during withdrawal of life-sustaining therapy, allograft ischemic parameters, and more, and examines ongoing controversies across preoperative, peri-withdrawal, and intraoperative phases. By synthesizing current practices and identifying critical gaps, we aim to support the development of more standardized, ethically robust, and clinically effective protocols for DCD-HT.

BACKGROUND/UNASSIGNED:Related to a lack of a perceived fiduciary obligation, the health insurance industry has not historically been supportive of the efforts of providers who treat pain. In the United States and several other nations, the early years of this millennium were marked by a prescription opioid crisis, resulting in abuse, addiction and hundreds of thousands of deaths. OBJECTIVE/UNASSIGNED:The temporal contiguity between payors' withdrawal of support for interdisciplinary pain management and the onset of the prescription opioid crisis has been noted in the literature, as were payors' global instruction to physicians to just prescribe medications. STUDY DESIGN/UNASSIGNED:This is a perspective on health policy. RESULTS/UNASSIGNED:With the explosion of interventional technology and techniques over the past decades, physicians have been able to provide more effective and certainly safer pain management to sufferers of chronic pain. However, over the past several years, payors' willingness to reimburse for previously covered interventional treatments has waned, causing considerable suffering for patients and frustration for clinicians. These payors include the Centers for Medicare and Medicaid Services as well as private insurers. LIMITATIONS/UNASSIGNED:This is a perspective article with limited literature on the topic. CONCLUSION/UNASSIGNED:At present, clinicians are being told to resort to medications, despite a dearth of novel, safe pharmacological agents appropriate for chronic pain management. The availability of restorative, behavioral and alternative medicine approaches is limited in terms of insurance reimbursement. Accordingly, noncoverage of interventional approaches to chronic pain management has the potential to indirectly result in another prescription opioid crisis, which neither our patients nor providers deserve.

ObjectiveTo systematically evaluate donor site pain control interventions for iliac crest-based secondary alveolar bone grafting (ABG).DesignSystematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.SettingOriginal scientific investigations.Patients, ParticipantsPatients undergoing iliac crest-based secondary ABG.InterventionsDonor site analgesics and minimally invasive harvest techniques.Main Outcome Measure(s)Pain scores, opioid consumption, length of stay, ambulation variables, complications, and pain assessment scales used.Results33 studies met the inclusion criteria, encompassing 1925 patients. The most frequently studied methods for donor site pain control were analgesic infusion pumps or catheters (8, 24.2%), local bupivacaine (8, 24.2%), local liposomal bupivacaine (5, 15.2%), transversus abdominis plane blocks (4, 12.1%), and bupivacaine-soaked sponges (4, 12.1%). Most studies evaluated pain scores (21, 63.6%), opioid consumption (17, 51.5%), and length of stay (17, 51.5%). The most used pain assessment scales were generic numeric (1-10) pain rating scales (9, 27.3%), the Visual Analog Scale (9, 27.3%), and the Wong-Baker FACES Scale (3, 9.1%). Use of locally administered liposomal bupivacaine was associated with improved donor site pain scores, reduced opioid consumption, and shorter length of stay. Alternative interventions exhibited variable efficacy.ConclusionsAcross the available evidence, despite notable variations in bone graft harvest techniques, intraoperative medication dosages, and pain assessment methods, locally administered liposomal bupivacaine was associated with favorable donor site pain control. The significant heterogeneity in the documentation of postoperative pain highlights the need for standardized pain assessment protocols to reliably assess the relative efficacy of donor site pain control strategies for secondary ABG.

Previous epidemiological studies have shown that E-cigarette and tobacco users are more likely to develop COVID-19 symptoms than non-users. To investigate the underlying mechanisms, we examined the effects of nicotine, the major component of tobacco and E-cigarette, and its major metabolite, cotinine, on the susceptibility of human respiratory epithelial cells to SARS-CoV-2 infection. We found that pre-treatment with nicotine and cotinine significantly and additively enhanced viral infection. While nicotine increased the expression of the viral receptor ACE2 and the serine protease TMPRSS2, cotinine upregulated cysteine protease cathepsin B and promoted viral spike protein cleavage. These findings suggest that nicotine and cotinine enhance SARS-CoV-2 infection at the cell entry stage through distinct mechanisms. Using a SARS-CoV-2 pseudovirus system, we further investigated the effects and mechanisms of nicotine and cotinine on viral entry. We found that both compounds enhanced pseudovirus infection, but with different time courses. Nicotine's effect correlated with the upregulation of ACE2 and TMPRSS2, whereas cotinine's effect corresponded with increased cathepsin B and viral spike protein cleavage. The cathepsin B inhibitor E64d completely abolished cotinine-enhanced viral spike protein cleavage and viral entry. In contrast, ACE2 and TMPRSS2 inhibitors (chloromethylketone and camostat) had limited effects on viral spike protein cleavage and only partially reduced the viral entry enhancement induced by nicotine and cotinine. These results indicate that nicotine promotes virus-receptor binding and cell entry, while cotinine facilitates viral entry through cathepsin B-mediated spike protein cleavage.IMPORTANCEThis study highlights the potential risks of tobacco and E-cigarette use in increasing susceptibility to COVID-19. We show that the major neurostimulant in tobacco and E-cigarette, nicotine, and its metabolite, cotinine, additively enhance SARS-CoV-2 infection in human respiratory epithelial cells by promoting viral entry. Specifically, nicotine and cotinine upregulate the expression of distinct, yet complementary sets of key cellular proteins required for viral entry. These findings suggest that both tobacco smoking and E-cigarette vaping may exacerbate COVID-19 infection rates and severity and provide new insights into how nicotine and cotinine contribute to viral susceptibility. This research underscores the need for public health measures to address the heightened risk posed by tobacco smoking and E-cigarette vaping to encounter the SARS-CoV-2 infection.

AIM/OBJECTIVE:The "2026 HRS Expert Consensus Statement Update on Cardiovascular Implantable Electronic Device Lead Management and Extraction" provides updated recommendations to guide clinicians in the management of cardiovascular implantable electronic device (CIED) leads. BACKGROUND:Since the publication of the "2017 HRS Expert Consensus Statement on Cardiovascular Implantable Electronic Device Lead Management and Extraction," the field has evolved quickly. New evidence on CIED lead management and the blooming development of new CIED technologies, including leadless pacing and implantable cardioverter-defibrillator leads implanted outside the vascular system and new lumenless pacing leads and lead extraction tools, have contributed to the field's rapid evolution. METHODS AND RESULTS/RESULTS:A comprehensive literature search was conducted in accordance with the Institute of Medicine standards. The writing committee reviewed evidence gathered through electronic literature searches encompassing clinical trials, original studies, and meta-analyses conducted on human subjects published in English from MEDLINE, PubMed, Embase, and the Cochrane Library up to December 2024. The comprehensive literature review supports each evidence-based recommendation and is compiled in the evidence tables. A predefined threshold of >70% approval for each recommendation was required, with a quorum of two-thirds of the writing committee. The final mean consensus of 108 recommendations was 93.61%. DISCUSSION/CONCLUSIONS:The recommendations from the "2017 Expert Consensus Statement on Cardiovascular Implantable Electronic Device Lead Management and Extraction" have been updated with new evidence to guide clinicians. The new recommendations address the latest CIED technologies with the advantages over transvenous leads; new evidence supporting diagnosis, treatment, and prevention for CIED infection; appropriate lead management in transcatheter tricuspid valve replacement for tricuspid regurgitation; and standardization of transvenous lead extraction approach, protocol, and facilities to improve the outcomes of CIED lead management and extraction.

Heart transplantation outcomes have tremendously improved over the nearly fifty years that the procedure has been performed. As demand continues to grow, there is a persistent shortage of organs. Compounding this is the potential for organs to deteriorate with increasing preservation and transport times. New technologies have been developed to address these issues. These include novel physiologic preservation solutions and preservation devices (which range from those that optimize temperature control to those that use machine perfusion or combinations of these facets) to minimize the risk of ischemic injury. Research is ongoing into these techniques and their potential to improve outcomes by protecting donor organs (particularly in cases of prolonged ischemic times) and expand the donor pool by better preserving grafts from marginal and/or donation after circulatory death donors. There is even research into utilizing these technologies to enable safe cardiac xenograft implantation as well as their role in beating heart transplantation.

BACKGROUND:In this planned analysis of a study on the effects of dorsal root ganglion stimulation (DRGS) on sleep and functional outcomes, we evaluated device-related complications, with a focus on lead fracture. MATERIALS AND METHODS/METHODS:Data were extracted for adult patients treated with DRGS between January 2018 and February 2025 from a clinical registry; patients with ≥1 follow-up were included. Device-related adverse events, including lead fracture and migration, were identified and cross-checked against clinic notes, operative reports, and device interrogation data. Cumulative fracture probability was determined with Kaplan-Meier estimation; multivariable Cox regression was used to identify predictors of fracture. A standardized fascial anchoring technique was implemented in mid-2020 and its influence on events was assessed. RESULTS:; 95% CI, 0.893-0.996; p = 0.037); age, sex, lead level, laterality, number of leads, and primary diagnosis were not significant predictors. Crude incidence of fracture was 11.9% in unanchored leads versus 8.6% in anchored leads; however, time-to-event curves were similar, and anchoring was not an independent predictor. Most patients with fractured leads underwent revision (17/21); four experienced a second fracture. Lead migration occurred in four of 375 leads (1.2%) among four patients, mostly before routine anchoring was implemented at our center in June 2020. Five patients (5.4%) underwent explantation. CONCLUSION/CONCLUSIONS:Lead fracture remains a hinderance to long-term durability of DRGS therapy although events were usually manageable with restoration of therapeutic effect. Anchoring did not change fracture risk but coincided with low migration rates. BMI was the only significant predictor of fracture.

INTRODUCTION/BACKGROUND:Technological advances in organ preservation and reconditioning have enabled increased use of donation after circulatory death (DCD) organs. We aimed to characterize temporal trends in pediatric DCD (pDCD) in the United States. METHODS:We used Organ Procurement and Transplantation Network data to identify all pediatric (age < 18 years) deceased organ donors in the US, 2000-2025. We calculated the number and proportion of pediatric donation after brain death (pDBD) and pDCD donors by year. We calculated the number and type of recovered and transplanted pDBD and pDCD organs by year. RESULTS:The annual number of pDBD donors fell from 985 in 2000 to 530 in 2025, whereas pDCD donors increased from 21 to 244. The rise in pDCD recovery was observed for all organs: 32%, 19%, 16%, 14%, and 12% of recovered pediatric kidneys, livers, lungs, hearts, and pancreata by 2025. Among transplants with pediatric recipients in 2000, there was 1 pDCD liver transplant and no pDBD kidney, heart, lung, or pancreas transplants. By 2025, pDCD transplants accounted for 3%, 2%, and 8% of kidney, liver, and heart transplants with pediatric recipients. CONCLUSION/CONCLUSIONS:pDBD donors have fallen over the last 25 years, whereas pDCD donors have increased over 10-fold over the same period. Given the ongoing need for pediatric organ transplantation and the ethical importance of preserving opportunities for donation, there is an urgent need to develop a parallel communication and ethical framework to support families, clinicians, and transplant teams in navigating these donation opportunities.

BACKGROUND:Chronic axial spinal pain is one of the leading causes of disability. The literature demonstrates that expenditures for low back and neck pain continue to rise, not only in parallel with increasing disability, but also with escalating healthcare costs, accounting for the highest spending among multiple disease categories. Based on current evidence utilizing controlled diagnostic blocks, facet joints, nerve root dura, and sacroiliac joints have been identified as potential sources of spinal pain. STUDY DESIGN/METHODS:A systematic review of the diagnostic accuracy of spinal facet joint nerve blocks. OBJECTIVE:To determine the diagnostic accuracy of spinal facet joint nerve blocks in chronic spinal pain. METHODS:Methodological quality of the included studies was assessed using the Quality Appraisal of Reliability Studies (QAREL) instrument. Only diagnostic accuracy studies meeting at least 50% of the predefined inclusion criteria were included in the analysis.The strength of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Levels of evidence were classified using a modified best evidence synthesis, ranging from Level I to Level V.Data sources included relevant literature identified through PubMed and other electronic searches published from 1966 through September 2025, Cochrane reviews, and manual searches of the bibliographies of primary and review articles. OUTCOME MEASURES/METHODS:Eligible studies were required to use placebo-controlled or comparative local anesthetic blocks. A positive diagnostic standard was defined as at least 50% pain relief from baseline scores along with the ability to perform previously painful movements. RESULTS:The available evidence demonstrated Level I for lumbar facet joint nerve blocks, based on 18 studies employing dual diagnostic blocks, demonstrating 75% to 80% pain relief, with an average prevalence of 16% to 45% and estimated or presumed false-positive rates of 25% to 50%.Evidence for the diagnosis of cervical facet joint pain using cervical facet joint nerve blocks is Level II, derived from 12 controlled diagnostic accuracy studies, showing substantial heterogeneity and internal inconsistency. Reported prevalence ranged from 36% to 67% with ≥ 80% pain relief and estimated or presumed false-positive rates of 26% to 63%.The level of evidence for the diagnostic accuracy of thoracic facet joint nerve blocks is Level II, based on 3 studies using dual diagnostic blocks, demonstrating 80% or greater pain relief, with prevalence ranging from 34% to 48% and estimated or presumed false-positive rates ranging from 42% to 58%. LIMITATIONS/CONCLUSIONS:Limitations of this systematic review include the limited number of studies involving the thoracic spine, ongoing debate regarding the appropriate reference standard, challenges in determining false-positive rates, concerns regarding the appropriateness of diagnostic blocks, the scarcity of recent publications, and issues related to clinical utility. CONCLUSION/CONCLUSIONS:There is Level I evidence for the diagnostic accuracy of lumbar facet joint nerve blocks and Level II evidence for cervical and thoracic facet joint nerve blocks in the evaluation of chronic spinal pain.