Citations

Background: High-frequency (10-kHz) spinal cord stimulation (SCS) continues to be an emerging therapy in chronic pain management. The same complications that plagued earlier SCS systems may affect newer stimulation technologies, although there is limited data on the type of complications and surgical management of these complications. Objective: The aim of this study was to systematically examine real-world complications associated with 10-kHz SCS reported on the Manufacturer and User Facility Device Experience (MAUDE) database. Materials and Methods: The MAUDE database was queried for entries reported between January 1, 2016 and December 31, 2020. Entries were classified into procedural complications, device-related complications, patient complaints, surgically managed complications, serious adverse events, and/or other complications. Primary outcomes included type and frequency of complications, and surgical management of complications. Results: A total of 1651 entries were analyzed. Most entries were categorized as procedural complications (72.6%), followed by serious adverse events (10.5%), device-related complications (10.5%), and patient complaints (9.9%). Most complications were managed surgically with explant (50.9%) rather than revision (5.0%) or incision/drainage (6.6%). Of procedural complications, the most common entries included non-neuraxial infection (52.9%), new neurological symptoms (14.7%), and dural puncture (9.5%). Of device-related complications, the most common entries included lead damage (41.6%), erosion (18.5%), and difficult insertion (11.5%). Conclusion: This retrospective 5-year analysis of complications from10-kHz SCS provides a real-world assessment of safety data unique for this stimulation modality. This analysis may help inform future clinical decisions, lead to device enhancement and optimization, and improve mitigation of risks to provide safe and efficacious use of 10-kHz SCS.

Aims Remote monitoring of pulmonary artery pressure has reduced heart failure (HF) hospitalizations in chronic HF as elevation of pulmonary artery pressure provides information that can guide treatment. The venous system is characterized by high capacitance, thus substantial increases in intravascular volume can occur before filling pressures increase. The inferior vena cava (IVC) is a highly compliant venous conduit and thus a candidate for early detection of change in intravascular volume. We aimed to compare IVC cross‐sectional area using a novel sensor with cardiac filling pressures during experimental manipulation of volume status, vascular tone, and cardiac function. Methods and results Experiments were conducted in sheep to manipulate volume status (colloid infusion), vascular tone (nitroglycerin infusion) and cardiac function (rapid cardiac pacing). A wireless implantable IVC sensor was validated ex‐vivo and in‐vivo , and then used to measure the cross‐sectional area of the IVC. Right‐ and left‐sided cardiac filling pressures were obtained via right heart catheterization. The IVC sensor provided highly accurate and precise measurements of cross‐sectional area in ex‐vivo and in‐vivo validation. IVC area changes were more sensitive than the corresponding changes in cardiac filling pressures during colloid infusion ( p < 0.001), vasodilatation ( p < 0.001) and cardiac dysfunction induced by rapid pacing ( p ≤ 0.02). Conclusions Inferior vena cava area can be remotely and accurately measured in real time with a wireless implantable sensor. Changes in IVC area are more sensitive than corresponding changes in filling pressures following experimental volume loading and fluid redistribution. Additional research is warranted to understand if remote monitoring of the IVC may have advantages over pressure‐based monitors in HF.

Histiocytic neoplasms are rare hematologic disorders accounting for less than 1% of cancers of the soft tissue and lymph nodes. Clinical presentation and prognosis of these disorders can be highly variable, leading to challenges for diagnosis and optimal management of these patients. Treatment often consists of systemic therapy, and recent studies support use of targeted therapies for patients with these disorders. Observation (“watch and wait”) may be sufficient for select patients with mild disease. These NCCN Guidelines for Histiocytic Neoplasms include recommendations for diagnosis and treatment of adults with the most common histiocytic disorders: Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease.

The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.

Longitudinal observational cohort studies are being conducted worldwide to understand cognition, biomarkers, and the health of the aging population better. Cross-cohort comparisons and networks of registries in Alzheimer’s disease (AD) foster scientific exchange, generate insights, and contribute to the evolving clinical science in AD. A scientific working group was convened with invited investigators from established cohort studies in AD, in order to form a research collaboration network as a resource to address important research questions. The Connecting Cohorts to Diminish Alzheimer’s Disease (CONCORD-AD) collaboration network was created to bring together global resources and expertise, to generate insights and improve understanding of the natural history of AD, to inform design of clinical trials in all disease stages, and to plan for optimal patient access to disease-modifying therapies once they become available. The network brings together expertise and data insights from 7 cohorts across Australia, Europe, and North America. Notably, the network includes populations recruited through memory clinics as well as population-based cohorts, representing observations from individuals across the AD spectrum. This report aims to introduce the CONCORD-AD network, providing an overview of the cohorts involved, reporting the common assessments used, and describing the key characteristics of the cohort populations. Cohort study designs and baseline population characteristics are compared, and available cognitive, functional, and neuropsychiatric symptom data, as well as the frequency of biomarker assessments, are summarized. Finally, the challenges and opportunities of cross-cohort studies in AD are discussed.

IntroductionWe calculate the financial margins for delivery of routine antenatal care as reimbursed by Medicaid. Prenatal care cost varies with overhead, health care provider type, and number of office visits. Antenatal care is only one component of the global maternity bundle, which also includes intrapartum and postpartum care.MethodsTime for provision of low‐risk antenatal care was determined prospectively from a study of 133 low‐risk pregnant patients. Health care provider time cost was estimated using mean wages for obstetricians and midwives. Margins were estimated by subtracting cost of provider services and overhead for the antenatal component of maternity care from total Medicaid reimbursement for the pregnancy global package (CPT 59400) using 2015 dollars. The maternity bundle elements of routine prenatal laboratory tests, ultrasounds, intrapartum care, and postpartum care were not included in our analysis of cost components.ResultsPatients received an average of 215 minutes of direct provider time per pregnancy. At the 50th percentile for physician payment and assuming overhead is 53.4% of revenue, practice margins varied by state from −$1067 to +$675, with a median of −$357. Median margins for midwifery care were +$15, with a range of −$579 to +$885. Margins were negative if overhead costs exceeded 33% of revenue for physician care and 55% of revenue for midwifery care.DiscussionIn many states, Medicaid reimbursement for the global maternity package is less than the actual cost of antenatal care alone. Improving reimbursement or decreasing costs is necessary to make maternity care more cost‐effective.

Background Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here. Methods Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80%, target enrollment was 325 patients. Results For randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95% CI: 0.37 to 1.19), 0.72 (95% CI: 0.35 to 1.50), and 1.19 (95% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients <60 years old (HR=0.324 (95% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95% CI: 0.255 to 0.952)). Conclusions Seviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas. Trial registration number NCT01546571.

Abstract Background The current global pandemic has created unprecedented challenges in the blood supply network. Given the recent shortages, there must be a civilian plan for massively bleeding patients when there are no blood products on the shelf. Recognizing that the time to death in bleeding patients is less than 2 h, timely resupply from unaffected locations is not possible. One solution is to transfuse emergency untested whole blood (EUWB), similar to the extensive military experience fine‐tuned over the last 19 years. While this concept is anathema in current civilian transfusion practice, it seems prudent to have a vetted plan in place. Methods and Materials During the early stages of the 2020 global pandemic, a multidisciplinary and international group of clinicians with broad experience in transfusion medicine communicated routinely. The result is a planning document that provides both background information and a high‐level guide on how to emergently deliver EUWB for patients who would otherwise die of hemorrhage. Results and Conclusions Similar plans have been utilized in remote locations, both on the battlefield and in civilian practice. The proposed recommendations are designed to provide high‐level guidance for experienced blood bankers, transfusion experts, clinicians, and health authorities. Like with all emergency preparedness, it is always better to have a well‐thought‐out and trained plan in place, rather than trying to develop a hasty plan in the midst of a disaster. We need to prevent the potential for empty shelves and bleeding patients dying for lack of blood.

Background: Although graft choice may be limited in the revision setting based on previously used grafts, most surgeons believe that graft choice for anterior cruciate ligament (ACL) reconstruction is an important factor related to outcome. Hypothesis: In the ACL revision setting, there would be no difference between autograft and allograft in rerupture rate and patient-reported outcomes (PROs) at 6-year follow-up. Study Design: Cohort study; Level of evidence, 2. Methods: Patients who had revision surgery were identified and prospectively enrolled in this cohort study by 83 surgeons over 52 sites. Data collected included baseline characteristics, surgical technique and pathology, and a series of validated PRO measures. Patients were followed up at 6 years and asked to complete the identical set of PRO instruments. Incidence of additional surgery and reoperation because of graft failure were also recorded. Multivariable regression models were used to determine the predictors (risk factors) of PROs, graft rerupture, and reoperation at 6 years after revision surgery. Results: A total of 1234 patients including 716 (58%) men were enrolled. A total of 325 (26%) underwent revision using a bone-patellar tendon-bone (BTB) autograft; 251 (20%), soft tissue autograft; 289 (23%), BTB allograft; 302 (25%), soft tissue allograft; and 67 (5%), other graft. Questionnaires and telephone follow-up for subsequent surgery information were obtained for 809 (66%) patients, while telephone follow-up was only obtained for an additional 128 patients for the total follow-up on 949 (77%) patients. Graft choice was a significant predictor of 6-year Marx Activity Rating Scale scores ( P = .024). Specifically, patients who received a BTB autograft for revision reconstruction had higher activity levels than did patients who received a BTB allograft (odds ratio [OR], 1.92; 95% CI, 1.25-2.94). Graft rerupture was reported in 5.8% (55/949) of patients by their 6-year follow-up: 3.5% (16/455) of patients with autografts and 8.4% (37/441) of patients with allografts. Use of a BTB autograft for revision resulted in patients being 4.2 times less likely to sustain a subsequent graft rupture than if a BTB allograft were utilized ( P = .011; 95% CI, 1.56-11.27). No significant differences were found in graft rerupture rates between BTB autograft and soft tissue autografts ( P = .87) or between BTB autografts and soft tissue allografts ( P = .36). Use of an autograft was found to be a significant predictor of having fewer reoperations within 6 years compared with using an allograft ( P = .010; OR, 0.56; 95% CI, 0.36-0.87). Conclusion: BTB and soft tissue autografts had a decreased risk in graft rerupture compared with BTB allografts. BTB autografts were associated with higher activity level than were BTB allografts at 6 years after revision reconstruction. Surgeons and patients should consider this information when choosing a graft for revision ACL reconstruction.