Management of Neuropathic Pain with Neurectomy Combined with Dermal Sensory Regenerative Peripheral Nerve Interface (DS-RPNI).

Neuropathic pain affects a large percentage of the U.S. population and leads to tremendous morbidity. Numerous nonsurgical and surgical treatments have been utilized to try and manage neuropathic pain with varying degrees of success. Recent research investigating ways to improve prosthetic control have identified new mechanisms for preventing neuromas in both motor and sensory nerves with free muscle and dermal grafts, respectively. These procedures have been used to treat chronic neuropathic pain in nonamputees, as well, in order to reduce failure rates found with traditional neurectomy procedures. Herein, we focus our attention on Dermal Sensory-Regenerative Peripheral Nerve Interfaces (DS-RPNI, free dermal grafts) which can be used to physiologically "cap" sensory nerves following neurectomy and have been shown to significantly decrease neuropathic pain.

Unmasked Neuropathic Pain After Neurectomy: A Case Series and Review of the Literature.

Localization of neuropathic pain to a specific peripheral nerve origin relies on patient history, physical examination, and nerve blocks. Neurectomy of the involved nerve(s) can successfully alleviate patients' pain. However, a subset of patients postoperatively describe persistent pain, but say that the pain "moved" to a new location (eg, from the dorsum of the foot to the lateral foot). This may be viewed as a treatment failure by the patient and surgeon alike. Further investigation, however, may localize the new pain to an additional, separate peripheral nerve injury, which was previously unrecognized by both parties. The mechanism involved is that of pain masking and unmasking. Successful treatment of the more prominent pain stimulus allows for recognition of a second, less-offending peripheral nerve injury. As the field of surgical treatment of chronic peripheral neuropathic pain advances, it is important to identify and define specific nuances of diagnosis and treatment via neurectomy. The term "diffuse noxious inhibitory control," used to describe the pain-inhibits-pain pathway, may help explain the phenomenon of masking, whereby one pain generator is more prominent and shields another site from recognition and subsequent diagnosis. In this context, unmasked pain should be considered as a potential source of surgical treatment failure. We present a series of patients who, following improvement in the initial location of their pain, reported pain in a distinctly new peripheral nerve distribution, leading to reoperation.

Human Performance Optimization: A Framework for the Military Health System.

The Department of Defense (DoD) is increasingly dependent on highly technological weapon systems, but the human is still at the heart of our war-fighting efforts. In order to maintain an effective fighting force, we must optimize and sustain human performance, which is defined as the successful completion of a specified task within an available performance capacity that meets or exceeds the mission demands. When health and performance are optimized and sustained, the costs of warfighter care and disability compensation are reduced and the quality of life is enhanced. Therefore, we propose that the Military Health System (MHS) reshape its focus on disease and injury treatment and prevention to embrace health enhancement for optimal human performance in a technology-rich battle space. This commentary develops a high-level strategy and policy framework to enable the MHS to optimize health and human performance for all DoD warfighters. We conducted a review of human performance literature, assessed existing health programs across the services, and conducted interviews with MHS and Line representatives. We found that the MHS has thus far met warfighter needs in a haphazard fashion. We propose an orchestrated approach to warfighter health and performance across the DoD and a more substantial partnership between Total Force Fitness and the MHS. We provide a notional concept for how the parts of this system could interact and a strategic framework for the delivery of health and performance to the warfighter.

The PARTNER 3 Bicuspid Registry for Transcatheter Aortic Valve Replacement in Low-Surgical-Risk Patients.

OBJECTIVES: The study compared 1-year outcomes between transcatheter aortic valve replacement (TAVR) patients with bicuspid aortic valve (BAV) morphology and clinically similar patients having tricuspid aortic valve (TAV) morphology. BACKGROUND: There are limited prospective data on TAVR using the SAPIEN 3 device in low-surgical-risk patients with severe, symptomatic aortic stenosis and bicuspid anatomy. METHODS: Low-risk, severe aortic stenosis patients with BAV were candidates for the PARTNER 3 (Placement of Aortic Transcatheter Valves 3) (P3) bicuspid registry or the P3 bicuspid continued access protocol. Patients treated in these registries were pooled and propensity score matched to TAV patients from the P3 randomized TAVR trial. Outcomes were compared between groups. The primary endpoint was the 1-year composite rate of death, stroke, and cardiovascular rehospitalization. RESULTS: Of 320 total submitted BAV patients, 169 (53%) were treated, and most were Sievers type 1. The remaining 151 patients were excluded caused by anatomic or clinical criteria. Propensity score matching with the P3 TAVR cohort (496 patients) yielded 148 pairs. There were no differences in baseline clinical characteristics; however, BAV patients had larger annuli and they experienced longer procedure duration. There was no difference in the primary endpoint between BAV and TAV (10.9% vs 10.2%; P = 0.80) or in the rates of the individual components (death: 0.7% vs 1.4%; P = 0.58; stroke: 2.1% vs 2.0%; P = 0.99; cardiovascular rehospitalization: 9.6% vs 9.5%; P = 0.96). CONCLUSIONS: Among highly select bicuspid aortic stenosis low-surgical-risk patients without extensive raphe or subannular calcification, TAVR with the SAPIEN 3 valve demonstrated similar outcomes to a matched cohort of patients with tricuspid aortic stenosis.

Effective Treatment of Chronic Mastectomy Pain with Intercostal Sensory Neurectomy.

SUMMARY: Chronic postmastectomy pain affects up to 40 percent of patients and leads to diminished quality of life and increased risk of opioid dependence. The cause of this pain is incompletely understood; however, one hypothesis is that direct injury to cutaneous intercostal nerves at the time of mastectomy and/or reconstruction leads to chronic pain. As a result, proximal neurectomy of the involved sensory nerve(s) has been suggested to be effective for these patients. The purpose of this study was to determine whether chronic pain in postmastectomy patients can be diagnosed reliably in an office setting and pain reduced by intercostal sensory neurectomy. The authors performed a retrospective review of seven patients with a history of breast surgery and chronic pain who underwent intercostal neurectomy combined with muscle or dermal wrapping of the proximal end of the resected nerve. All patients were diagnosed by history and physical examination, and suspected nerves were further identified with local anesthetic nerve blocks. An average of 3.14 neurectomies were performed per patient (range, one to six). There was a significant reduction in visual analogue scale pain scores following surgery, from 9 preoperatively to 1 postoperatively (p = 0.02). Eighty-six percent of patients were pain-free or "considerably improved" at their latest follow-up appointment (average, 6.14 months). It is concluded that intercostal sensory nerve injury at the time of mastectomy and/or reconstruction can lead to chronic mastectomy pain, which can be easily diagnosed and effectively treated with intercostal neurectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Coronary circulatory function with increasing obesity: A complex U-turn.

AIMS: The aim of this investigation was to explore and characterize alterations in coronary circulatory function in function of increasing body weight with medically controlled cardiovascular risk factors and, thus, "metabolically" unhealthy obesity. MATERIALS AND METHODS: We prospectively enrolled 106 patients with suspected CAD but with normal stress-rest myocardial perfusion on 13 N-ammonia PET/CT and with medically controlled or no cardiovascular risk factors. 13 N-ammonia PET/CT concurrently determined myocardial blood flow (MBF) during pharmacologically induced hyperaemia and at rest. Based on body mass index (BMI), patients were grouped into normal weight (BMI: 20.0-24.9 kg/m2 , n = 22), overweight (BMI: 25.0-29.9 kg/m2 , n = 27), obese (BMI: 30.0-39.9 kg/m2 , n = 31), and morbidly obese (BMI ≥ 40kg/m2 , n = 26). RESULTS: Resting MBF was comparable among groups (1.09 ± 0.18 vs. 1.00 ± 0.15 vs. 0.96 ± 0.18 vs.. 1.06 ± 0.31 ml/g/min; p = .279 by ANOVA). Compared to normal weight individuals, the hyperaemic MBF progressively decreased in in overweight and obese groups, respectively (2.54 ± 0.48 vs. 2.02 ± 0.27 and 1.75 ± 0.39 ml/g/min; p < .0001), while it increased again in the group of morbidly obese individuals comparable to normal weight (2.44 ± 0.41 vs. 2.54 ± 0.48 ml/g/min, p = .192). The BMI of the study population correlated with the hyperaemic MBF in a quadratic or U-turn fashion (r = .34, SEE = 0.46; p ≤ .002). CONCLUSIONS: The U-turn of hyperaemic MBF from obesity to morbid obesity is likely to reflect contrasting effects of abdominal versus subcutaneous adipose tissue on coronary circulatory function indicative of two different disease entities, but needing further investigations.

Optimal Medical Therapy as First-Line Therapy for Chronic Coronary Syndromes: Lessons from COURAGE, BARI 2D, FAME 2, and ISCHEMIA.

The chronic coronary syndromes (CCS) include patients with a classic history of angina pectoris in the presence of either risk factors for or known atherosclerotic coronary artery disease. Randomized, controlled trials conducted in the optimal medical therapy (OMT) era have convincingly demonstrated that adherence to the outdated paradigm focused on treatment of obstructive coronary disease with initial revascularization fails to reduce death or myocardial infarction and inconsistently reduces angina symptoms. Rather, OMT reduces events and improves symptoms and should be considered first-line treatment for patients with CCS.

Assessment of Nonfatal Myocardial Infarction as a Surrogate for All-Cause and Cardiovascular Mortality in Treatment or Prevention of Coronary Artery Disease: A Meta-analysis of Randomized Clinical Trials.

Importance: Although nonfatal myocardial infarction (MI) is associated with an increased risk of mortality, evidence validating nonfatal MI as a surrogate end point for all-cause or cardiovascular (CV) mortality is lacking. Objective: To examine whether nonfatal MI may be a surrogate for all-cause or CV mortality in patients with or at risk for coronary artery disease. Data Sources: In this meta-analysis, PubMed was searched from inception until December 31, 2020, for randomized clinical trials of interventions to treat or prevent coronary artery disease reporting mortality and nonfatal MI published in 3 leading journals. Study Selection: Randomized clinical trials including at least 1000 patients with 24 months of follow-up. Data Extraction and Synthesis: Trial-level correlations between nonfatal MI and all-cause or CV mortality were assessed for surrogacy using the coefficient of determination (R2). The criterion for surrogacy was set at 0.8. Subgroup analyses based on study subject (primary prevention, secondary prevention, mixed primary and secondary prevention, and revascularization), era of trial (before 2000, 2000-2009, and 2010 and after), and follow-up duration (2.0-3.9, 4.0-5.9, and ≥6.0 years) were performed. Main Outcomes and Measures: All-cause or CV mortality and nonfatal MI. Results: A total of 144 articles randomizing 1 211 897 patients met the criteria for inclusion. Nonfatal MI did not meet the threshold for surrogacy for all-cause (R2 = 0.02; 95% CI, 0.00-0.08) or CV (R2 = 0.11; 95% CI, 0.02-0.27) mortality. Nonfatal MI was not a surrogate for all-cause mortality in primary (R2 = 0.01; 95% CI, 0.001-0.26), secondary (R2 = 0.03; 95% CI, 0.00-0.20), mixed primary and secondary prevention (R2 = 0.001; 95% CI, 0.00-0.08), or revascularization trials (R2 = 0.21; 95% CI, 0.002-0.50). For trials enrolling patients before 2000 (R2 = 0.22; 95% CI, 0.08-0.36), between 2000 and 2009 (R2 = 0.02; 95% CI, 0.00-0.17), and from 2010 and after (R2 = 0.01; 95% CI, 0.00-0.09), nonfatal MI was not a surrogate for all-cause mortality. Nonfatal MI was not a surrogate for all-cause mortality in randomized clinical trials with 2.0 to 3.9 (R2 = 0.004; 95% CI, 0.00-0.08), 4.0 to 5.9 (R2 = 0.06; 95% CI, 0.001-0.16), or 6.0 or more years of follow-up (R2 = 0.30; 95% CI, 0.01-0.55). Conclusions and Relevance: The findings of this meta-analysis do not appear to establish nonfatal MI as a surrogate for all-cause or CV mortality in randomized clinical trials of interventions to treat or prevent coronary artery disease.

Surgical and percutaneous revascularization outcomes based on SYNTAX I, II, and residual scores: a long-term follow-up study.

BACKGROUND: The objective of this study was to evaluate the association of SYNTAX scores I, II, and residual with cardiovascular outcomes of patients undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) and compare both procedures in a long-term follow-up. METHODS: This is a retrospective single-center study from the MASS registry at the Heart Institute of the University of São Paulo, Brazil in which 969 patients with stable coronary artery disease undergoing CABG (559) or PCI (410) were included. We assessed the SYNTAX scores I, II and residual in both interventions. Clinical endpoints were the first occurrence of a composite of overall death, myocardial infarction, stroke, or repeat revascularization (MACCE) and the total occurrence of each component of MACCE. RESULTS: In the CABG sample, SSI had a median of 23 (IQR 17-29.5), median SSII of 25.4 (IQR 19.2-32.8), and median rSS of 2 (IQR 0-6.5); in PCI SSI had a median of 14 (IQR 10-19.1), median SSII of 28.7 (IQR 23-34.2), and median rSS of 4.7 (IQR 0-9). Total of 174 events were documented and CABG patients had a lower rate of MACCE (15.6% vs. 21.2%; adjusted HR 1.98; 95% CI 1.13-3.47; P = 0.016) and repeat revascularization (3.8% vs. 11.5%; adjusted HR 4.35; CI 95% 1.74-10.85; P = 0.002) compared with PCI. No SYNTAX score tertile found a difference in death rate between procedures. In a multivariate analysis, the rSS was an independent predictor for MACCE (HR 1.04; 95% CI 1.01-1.06; P = 0.001). Regarding death, the only independent predictors were ejection fraction and renal function. CONCLUSION: Surgical revascularization resulted in a more complete revascularization and lower rates of major cardiac or cerebrovascular events in a long-term follow-up. Also, grading the incompleteness of revascularization through the residual SYNTAX score identified a higher event rate, suggesting that complete revascularization is associated with a better prognosis.

Postoperative Atrial Fibrillation or Flutter Following Transcatheter or Surgical Aortic Valve Replacement: PARTNER 3 Trial.

OBJECTIVES: The aim of this study was to assess the incidence and prognostic impact of early and late postoperative atrial fibrillation or flutter (POAF) in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). BACKGROUND: There is an ongoing controversy regarding the incidence, recurrence rate, and prognostic impact of early (in-hospital) POAF and late (postdischarge) POAF in patients with AS undergoing TAVR or SAVR. METHODS: In the PARTNER (Placement of Aortic Transcatheter Valve) 3 trial, patients with severe AS at low surgical risk were randomized to TAVR or SAVR. Analyses were performed in the as-treated population excluding patients with preexistent atrial fibrillation or flutter. RESULTS: Among 781 patients included in the analysis, early POAF occurred in 152 (19.5%) (18 of 415 [4.3%] and 134 of 366 [36.6%] following TAVR and SAVR, respectively). Following discharge, 58 new or recurrent late POAF events occurred within 1 year following the index procedure in 55 of 781 patients (7.0%). Early POAF was not an independent predictor of late POAF following discharge (odds ratio: 1.04; 95% CI: 0.52-2.08; P = 0.90). Following adjustment, early POAF was not an independent predictor of the composite outcome of death, stroke, or rehospitalization (hazard ratio: 1.10; 95% CI: 0.64-1.92; P = 0.72), whereas late POAF was associated with an increased adjusted risk for the composite outcome (hazard ratio: 8.90; 95% CI: 5.02-15.74; P < 0.0001), irrespective of treatment modality. CONCLUSIONS: In the PARTNER 3 trial, early POAF was more frequent following SAVR compared with TAVR. Late POAF, but not early POAF, was significantly associated with worse outcomes at 2 years, irrespective of treatment modality.

Dermatosensory Peripheral Nerve Interfaces: Prevention of Pain Recurrence Following Sensory Neurectomy.

Chronic pain is a significant health care problem. Many patients' pain can be linked to a neuropathic origin, diagnosed with a thorough history and physical examination, and confirmed with a diagnostic nerve block. There are new procedures designed to address neuropathic pain from symptomatic neuromas by providing physiologic targets for regenerating axons following neurectomy. Dermal wrapping of the end of a sensory nerve following transection, a technique called dermatosensory peripheral nerve interface, may provide an optimal environment to prevent neuroma pain and reduce chronic neuropathic pain.

Association of Clinical Complications of Chemotherapy and Patient-Reported Outcomes After Immediate Breast Reconstruction.

Importance: Women undergoing immediate breast reconstruction often require chemotherapy. The effects of chemotherapy on reconstruction are not well described. Objective: To evaluate the association of neoadjuvant and adjuvant chemotherapy with complications and patient-reported outcomes (PROs) in immediate reconstruction. Design, Setting, and Participants: The Mastectomy Reconstruction Outcomes Consortium Study is a cohort study that prospectively assessed PROs and retrospectively evaluated complications in patients undergoing immediate implant-based or autologous reconstruction at 11 centers from January 1, 2012, to December 31, 2017. Women 18 years or older undergoing immediate reconstruction after mastectomy with 2 years of follow-up were included. Patients were excluded if they had prophylactic mastectomy; delayed reconstruction; mixed-timing reconstruction; mixed reconstruction; a latissimus dorsi, superior gluteal artery perforator, or inferior gluteal artery perforator flap; or both neoadjuvant and adjuvant chemotherapy. Data were analyzed from May 1 to June 30, 2018. Main Outcomes and Measures: Complications and PROs (satisfaction with breast and physical, psychosocial, and sexual well-being) using the BREAST-Q questionnaire, a validated, condition-specific PRO measure. Baseline patient characteristics were collected. Results: A total of 1881 women were included in the analysis (mean [SD] age, 49.9 [9.9] years). Of these, 1373 (73.0%) underwent implant-based procedures; 508 (27.0%), autologous reconstruction; 200 (10.6%), neoadjuvant chemotherapy; 668 (35.5%), adjuvant chemotherapy; and 1013 (53.9%), no chemotherapy. Patients without chemotherapy were significantly older (mean [SD] age, 51.6 [9.4] years; P < .001), and patients with chemotherapy were more likely to have received radiotherapy (108 of 200 [54.0%] for neoadjuvant chemotherapy and 321 of 668 [48.1%] for adjuvant chemotherapy; P < .001). Among the cohort undergoing implant-based reconstruction, the rates of any complication were significantly different, with higher rates seen for adjuvant (153 of 490 [31.2%]) and neoadjuvant (44 of 153 [28.8%]) chemotherapy compared with no chemotherapy (176 of 730 [24.1%]; P = .02). On multivariable analysis, these differences were not statistically significant. For autologous reconstruction, no significant differences in complications were observed. Controlling for clinical covariates, no significant differences were seen across chemotherapy groups for the BREAST-Q subscales except for sexual well-being in the implant cohort, in which adjuvant chemotherapy had significantly lower scores (ß, -4.97 [95% CI, -8.68 to -1.27]; P = .009). Conclusions and Relevance: In this cohort study, neither neoadjuvant nor adjuvant chemotherapy was associated with the likelihood of complications in patients undergoing implant-based or autologous reconstruction, and chemotherapy was not associated with patient satisfaction with reconstruction or psychosocial well-being. This information can help patients and clinicians make informed decisions about breast reconstruction in the setting of chemotherapy.

Design of Clinical Trials Evaluating Sedation in Critically Ill Adults Undergoing Mechanical Ventilation: Recommendations From Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) Recommendation III.

OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators. DESIGN: A 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process. PARTICIPANTS: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process. MEASUREMENTS AND MAIN RESULTS: The final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization. CONCLUSIONS: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials.