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CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition. [ABSTRACT FROM AUTHOR]

Optical coherence tomography allows for various measurements of skin but the utility of the device in determining properties of normal and wounded skin in diabetic patients is unknown. This single-site, non-randomized, observational study used an optical coherence tomography device to acquire skin images at 1305 nm, creating real-time image of 17 patient's skin and wounds 1 to 2 mm under the skin surface. Vertical B-scan, en-face and 3-D images were produced to calculate surface and dermal-epidermal junction roughness, the optical attenuation coefficient, a measure of light absorption and scattering, and blood flow metrics. In subjects with diabetes there was an increase in both the Ra (p <.02) and Rz (p <.001) of the wounded versus the control skin. In subjects without diabetes, there was an increase in both the Ra (p <.001) and Rz (p <.03) values of the wounded versus the control skin. At a depth of 0.6 mm across all subjects, there was an average decrease in blood flow of 63% from control to wounded skin. In subjects with diabetes, this decrease was 76%. In subjects without diabetes the decrease was 55%. The change in vasculature between control and wounded skin was associated with a p <.005. There was an increase in the Ra and Rz values and a decrease in blood flow between the wounded skin and control. The device determined a difference in the Ra and Rz values of both diabetic and healthy subjects' skin and a more pronounced decrease in blood flow in the wounds of patients with diabetes as opposed to those without. [ABSTRACT FROM AUTHOR]

The primary aim of the study is to determine risks for major lower extremity amputation after undergoing Vertical Contour Calcanectomy. Subanalysis was performed comparing patients who underwent Vertical Contour Calcanectomy who were fully ambulatory to those who were partially or nonambulatory postoperatively. Within the cohort of 63 patients included in the Vertical Contour Calcanectomy 85.71% (54/63) of patients had diabetes mellitus, 53.97% (34/63) had peripheral arterial disease, and 19.05% (12/63) had Charcot Neuroarthropathy. Multivariate logistic regression, found that (1) patients that underwent primary closure at the time of the Vertical Contour Calcanectomy, were 79.9% more likely (odds ratio [OR] 0.20; 95% confidence interval [CI] 0.04-0.96) to have limb salvage and that (2) female patients were 85.4% less likely compared to male patients (OR 0.15; 95% CI 0.02-0.99) to undergo major lower extremity amputation. Patients with coronary artery disease were 5.2 times more likely (OR 5.18; 95% CI 1.120-23.94) and patients that were nonambulatory preoperatively, were 10.3 times more likely (OR 10.28; 95% CI 1.60-66.26), to be partially or nonambulatory after Vertical Contour Calcanectomy. Primary closure at time of Vertical Contour Calcanectomy significantly decreases the risk of major lower extremity amputation, and diminished preoperative ambulatory status as well as coronary artery disease makes it less likely that patients return to full ambulation after Vertical Contour Calcanectomy. [ABSTRACT FROM AUTHOR]

Background: Short cementless femoral stems may allow for easier insertion with less dissection. The use of short stems with the anterior approach (AA) may be associated with a considerable perioperative fracture risk. Our aim was to evaluate whether patient-specific femoral and pelvic morphology and surgical technique, influence the perioperative fracture risk. Furthermore, we sought to describe important anatomical thresholds alerting surgeons.Methods: A single-center, multi-surgeon retrospective, case-control matched study was performed. Thirty nine periprosthetic fractures (3.4%) in 1,145 primary AA THAs using short cementless stems were identified. These were matched with 78 THA nonfracture controls for factors known to increase the fracture risk. A radiographic analysis using validated software measured femoral (canal flare index [CFI], morphological cortical index [MCI], and calcar-calcar ratio [CCR]) and pelvic (Ilium-ischial ratio [IIR], ilium overhang, and anterior superior iliac spine [ASIS] to greater trochanter distance) morphologies and surgical techniques (% canal fill). A multivariate and Receiver-Operator Curve (ROC) analysis was used to identify fracture predictors.Results: CFI (3.7 ± 0.6 vs 2.9 ± 0.4, P < .001) and CCR (0.5 ± 0.1 vs 0.4 ± 0.1, P = .006) differed. The mean IIR was higher in fracture cases (3.3 ± 0.6 vs 3.0 ± 0.5, P < .001). Percent canal fill was reduced in fracture cases (82.8 ± 7.6 vs 86.7 ± 6.8, P = .007). Multivariate and ROC analyses revealed a threshold CFI of 3.17 which was predictive of fracture (sensitivity: 84.6%/specificity: 75.6%). The fracture risk was 29 times higher when patients had CFI >3.17 and II ratio >3 (OR: 29.2 95% CI: 9.5-89.9, P < .001).Conclusion: Patient-specific anatomical parameters are important predictors of a fracture-risk. A careful radiographic analysis would help identify those at a risk of early fracture using short stems, and alternative stem options should be considered. [ABSTRACT FROM AUTHOR]

Hindfoot arthrodesis is often required for end-staged deformities, such as posterior tibial tendon dysfunction, osteoarthritis, or rheumatoid arthritis. Although the need for hindfoot arthrodesis is generally accepted in severe deformities, there is a debate whether a double or triple arthrodesis should be performed. The aim of our systematic review is to review the fusion rates and mean time to fusion in double and triple arthrodesis. A total of 184 articles were identified using the keyword search through the database of articles published from 2005 to 2017. After review by 3 physicians, a total of 13 articles met the eligibility criteria. The reason for double or triple arthrodesis within the studies were posterior tibial tendon dysfunction, tarsal coalition, degenerative joint disease, osteoarthritis, rheumatoid arthritis, Charcot Marie Tooth, Multiple Sclerosis, Polio, neuromuscular disorder, cerebral palsy, acrodystrophic neuropathy, clubfoot, post-traumatic, and seronegative arthropathy (spondyloarthritis). Within these 13 studies, there were a total of 343 (6-95) subjects extremities operated on. The overall fusion rate for double arthrodesis was 91.75% (289/315) compared to 92.86% (26/28) triple arthrodesis fusion rate, p value.8370. The mean time to fusion for double arthrodesis was 17.96 ± 7.96 weeks compared to 16.70 ± 8.18 weeks for triple arthrodesis, p value =.8133. There are risks associated with triple arthrodesis including increased surgical times, lateral wound complications, residual deformity, surgical costs and peri-articular arthritis. Given the benefits of double arthrodesis over triple arthrodesis and the nearly equivalent fusion rates and time to fusion, double arthrodesis is an effective alternative to triple arthrodesis. The authors of this systematic review recommend double arthrodesis as the hindfoot fusion procedure of choice. [ABSTRACT FROM AUTHOR]

Identification of bacteria by polymerase chain reaction (PCR) is known to be more sensitive than culture, which brings to question the clinical applicability of the results. In this study, we evaluate the ability of PCR to detect clinically relevant bacterial species in lower extremity wound infections requiring operative debridement, as well as the quantitative change in biodiversity and bacterial load reflected by PCR during the course of treatment. Thirty-four infected lower extremity were examined by analysis of 16S ribosomal RNA subunit and by culture. McNemar's test was used to measure the concordance of clinically relevant bacterial species identified by PCR compared to culture during each debridement. Change in wound biodiversity from initial presentation to final closure was evaluated by Wilcoxon signed-rank test. Kaplan-Meier survival curve was used to characterize change in measured bacterial load over the course of operative debridement. A total of 15 and 12 clinically relevant bacterial species were identified by PCR and culture, respectively. The most common bacterial species identified were Coagulase-negative Staphylococcus, Staphylococcus aureus, and Enterococcus spp. PCR was less likely to detect Enterococcus spp. on initial debridement and Coagulase-negative Staphylococcus on closure in this study population. A significant decrease in mean number of clinically relevant species detected from initial debridement to closure was reflected by culture (p =.0188) but not by PCR (p =.1848). Both PCR (p =.0128) and culture (p =.0001) depicted significant reduction in mean bacterial load from initial debridement to closure. PCR is able to identify common clinically relevant bacterial species in lower extremity surgical wound infections. PCR displays increased sensitivity compared to culture with relation to detection of biodiversity, rather than bacterial load. Molecular diagnostics and conventional culture may serve a joint purpose to assist with rendering clinical judgment in complex wound infections. [ABSTRACT FROM AUTHOR]

• In SARS-CoV-2 vaccine breakthrough infections requiring hospitalization, the majority had acute infection with no observed humoral response to the vaccine and developed severe disease • Serologic testing will help determine timing of infection and risk stratify prognosis in individuals with new vaccine breakthrough infections • In high risk individuals, selective serologic testing may be considered post vaccination to help guide maintained risk mitigation (eg, mask wearing, social distancing) even as measures are relaxed in local communities. While Severe Acute Respiratory Syndrome Coronavirus-2 vaccine breakthrough infections are expected, reporting on breakthrough infections requiring hospitalization remains limited. This observational case series report reviewed 10 individuals hospitalized with vaccine breakthrough infections to identify patient risk factors and serologic responses upon admission. Electronic medical records of BNT162b2 (Pfizer-BioNTech) or mRNA-1732 (Moderna) vaccinated patients admitted to Veterans Affairs Ann Arbor Healthcare System with newly diagnosed Coronavirus Infectious Disease 2019 (COVID-19) between March 15, 2021 and April 15, 2021 were reviewed. Patient variables, COVID-19 lab testing including anti-S IgM, anti-N IgG antibodies, and hospital course were recorded. Based on lab testing, infections were defined as acute infection or resolving/resolved infection. Of the 10 patients admitted with breakthrough infections, all were >70 years of age with multiple comorbidities. Mean time between second vaccine dose and COVID-19 diagnosis was 49 days. In the 7 individuals with acute infection, none had observed serologic response to mRNA vaccination, 5 developed severe disease, and 1 died. Three individuals had anti-N IgG antibodies and a high polymerase chain reaction cycle threshold value, suggesting resolving/resolved infection. Given the variability of vaccine breakthrough infections requiring hospitalization, serologic testing may impart clarity on timing of infection and disease prognosis. Individuals at risk of diminished response to vaccines and severe COVID-19 may also benefit from selective serologic testing after vaccination to guide risk mitigation strategies in a post-pandemic environment. [ABSTRACT FROM AUTHOR]

Diabetic foot infections (DFI) are an increasingly common cause of hospitalizations. Once hospitalized with DFI, many patients require some level of amputation, often undergoing multiple operations. With increasing importance on patient-centered metrics, self-reported health-related quality of life (HRQOL) tools have been developed. This prospective cohort study aimed assessed the impact of DFI on HRQOL. Two hundred twenty-four patients completed the 29-item Patient-Reported Outcome Measurement Information System (PROMIS) and 12-Item Short Form (SF-12) survey. Secondary outcomes using the Foot and Ankle Ability Measures survey were obtained and included in the analysis. The study group was comprised of hospitalized patients with DFIs (n = 120), and the control group was comprised of patients with diabetes who were evaluated for routine outpatient foot care (n = 104); diabetic foot screening, wound care, onychomycosis, and/or callosities. Using this cohort, a propensity score-matched sample of hospitalized patients with DFI (n = 35) and control group patients (n = 35) was created for comparative analysis. The 2-independent sample t test was used to test for group differences on each of the PROMIS subscale outcomes. Using PROMIS, we found that hospitalized patients with DFI reported significantly worse HRQOL in 6 of 7 subscales (physical function, anxiety, depression, fatigue, social role, pain intensity; p value range:.0001-.02) compared to outpatients with diabetes evaluated for routine foot care. There was no significant difference between the 2 groups on sleep disturbance (p =.22). Patients hospitalized for DFI report lower HRQOL compared to patients with diabetes receiving routine outpatient foot care. [ABSTRACT FROM AUTHOR]

Microglia and CNS-infiltrating macrophages play significant roles in the pathogenesis of neuroinflammatory and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Prolonged and dysregulated inflammatory responses by these innate immune cells can have deleterious effects on the surrounding CNS microenvironment, which can worsen neurodegeneration and demyelination. However, although chronic activation of pro-inflammatory microglia is maladaptive, other functional microglial subtypes play beneficial roles during CNS repair and regeneration. Therefore, there is a tremendous interest in understanding the underlying mechanism of the activation of these reparative/regenerative microglia. In this review, we focus on the potential role of PKC, a downstream signaling molecule of TREM2 and PLCγ2, and PKC modulators in promoting the activation of reparative/regenerative microglial subtypes as a novel therapy for neuroinflammatory and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The primary aim was to determine the rate of complications in patients with peripheral arterial disease and diabetic Charcot neuroarthropathy who underwent osseous reconstruction. Complications included delayed healing, dehiscence, and major lower extremity amputation. A review of patients with Charcot neuroarthropathy requiring reconstruction secondary to ulceration or acute infection was performed. Descriptive analysis compared outcomes between those with and without peripheral arterial disease. Bivariate analysis and multivariate logistic regression were analyzed for delayed healing, dehiscence, and major amputation. In a cohort of 284 patients with diabetic Charcot neuroarthropathy who underwent osseous reconstruction, the rate of peripheral arterial disease was 20.8% (59/284). Bivariate analysis for delayed healing found hypertension (p =.0352), peripheral arterial disease (p =.0051), and smoking history (p =.0276) to be statistically significant factors. Delayed healing was 2.012 times more likely in the presence of peripheral arterial disease [OR 2.012 (95% CI 1.088-3.720)]. Bivariate analysis for major lower extremity amputation found renal disease (0.0003) (renal disease: ESRD and CKD) and peripheral arterial disease (0.0001) to be statistically significant factors. Major amputation was 4.414 times more likely in the presence of peripheral arterial disease [OR 4.414 (95% CI 2.087-9.334)]. Peripheral arterial disease was identified in 20.8% (59/284) of diabetic patients who underwent Charcot osseous reconstruction. Peripheral arterial disease increased the risk of delayed healing by 2.012 fold, and increased the risk of major lower extremity amputation by 4.414 fold. The rates of complications in patients with peripheral arterial disease were significantly higher than those without peripheral arterial disease who underwent osseous reconstruction. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the intra- and inter-reader reliability of the 2 Charcot neuroarthropathy classifications (Sanders-Frykberg and Brodsky-Trepman), as well as Eichenholtz staging. We hypothesized that the inter-reader reliability, with respect to these 3 classification systems, would be moderate at best. Digital radiographic images were organized in a digital slide presentation without clinical information. All 5 reviewers underwent a standard training session administered by the principal investigator, reviewing 5 cases of Charcot neuroarthropathy. Images of 55 cases of Charcot neuroarthropathy and 5 normal cases were distributed to each of the 5 physicians electronically, who independently rated all 60 cases according to the 3 classification systems. The 95% confidence interval of the intraclass correlation coefficient estimate for Sanders-Frykberg was 0.9601 to 0.9833 at week 0 and 0.9579 to 0.9814 at week 8, which can be regarded as "excellent" reliability. For Trepman-Brodsky, the 95% confidence interval of the intraclass correlation coefficient estimate was 0.8463 to 0.9327 at week 0 and 0.8129 to 0.9226 at week 8, which can be regarded as "good" to "excellent" reliability. For Eichenholtz, the 95% confidence interval of the intraclass correlation coefficient estimate was 0.6841 to 0.8640 and 0.6931 to 0.8730 at weeks 0 and 8, respectively, which can be regarded as "moderate" to "good" reliability. The classification systems of Charcot neuroarthropathy are an important tool for communication among physicians. Based on the results at our institution, the Sanders-Frykberg classification exhibited the best inter-reader performance. The Trepman-Brodsky classification exhibited good to excellent reliability as well. The intraclass correlation coefficient of the Eichenholtz classification was moderate to good. [ABSTRACT FROM AUTHOR]

Charcot neuroarthropathy of the foot and ankle is associated with periarticular deformities and progressive radiographic changes. There have been studies analyzing the radiographic angulations and deformity progression in Charcot neuroarthropathy deformity. The aim of this paper is to provide systematic review of studies that evaluate foot and ankle radiographic parameters in patients with Charcot neuroarthropathy. A multidatabase search including, medline, EMBASE, Google Scholar, Cochrane Library, Clinicaltrials.gov and reference lists of included studies, was performed from 1980 to 2020. A total of 7 articles were included that analyzed radiographic angulations in Charcot neuroarthropathy deformity. The articles could be categorized into nonoperative angulation measurements, and pre- versus postoperative angulation measurements. The presence of ulcerations and the severity of the Charcot neuroarthropathy deformity were found to result from predominantly sagittal plane deformity. The deformity initiates with medial column collapse and progresses to continual lateral column collapse. Surgical intervention resulting in immediate postoperative improvement in angular measurements, however, without beaming of both the medial and lateral column, there was recurrence of the lateral column deformity. This systematic review of articles analyzing angular deformities in Charcot neuroarthropathy patients, demonstrates the progressive sagittal plane breakdown patterns of Charcot as well as the benefits of surgical intervention. [ABSTRACT FROM AUTHOR]

Background: Optimum management for the elderly acetabular fracture remains undefined. Open reduction and internal fixation (ORIF) in this population does not allow early weight-bearing and has an increased risk of failure. This study aimed to define outcomes of total hip arthroplasty (THA) in the setting of an acetabular fracture and compared delayed THA after acetabular ORIF (ORIF delayed THA) and acute fixation and THA (ORIF acute THA).Methods: All acetabular fractures in patients older than 60 years who underwent ORIF between 2007 and 2018 were reviewed (n = 85). Of those, 14 underwent ORIF only initially and required subsequent THA (ORIF delayed THA). Twelve underwent an acute THA at the time of the ORIF (ORIF acute THA). The ORIF acute THA group was older (81 ± 7 vs 76 ± 8; P < .01) but had no other demographic- or injury-related differences compared with the ORIF delayed THA group. Outcome measures included operative time, length of stay, complications, radiographic assessments (component orientation, leg-length discrepancy, heterotopic ossification), and functional outcomes using the Oxford Hip Score (OHS).Results: Operative time (P = .1) and length of stay (P = .5) for the initial surgical procedure (ORIF only or ORIF THA) were not different between groups. Four patients had a complication and required further surgeries; no difference was seen between groups. Radiographic assessments were similar between groups. The ORIF acute THA group had a significantly better OHS (40.1 ± 3.9) than the ORIF delayed THA group (33.6 ± 8.5) (P = .03).Conclusion: In elderly acetabulum fractures, ORIF acute THA compared favorably (a better OHS, single operation/hospital visit, equivalent complications) with ORIF delayed THA. We would thus recommend that in patients with risk factors for failure requiring delayed THA (eg, dome or roof impaction) that ORIF acute THA be strongly considered. [ABSTRACT FROM AUTHOR]

The objective of this study is to compare risk adjusted matched cohorts of Charcot neuroarthropathy patients who underwent osseous reconstruction with and without diabetes. The 2 groups were matched based on age, body mass index, hypertension, history of end-stage renal disease, and peripheral arterial disease. Bivariate analysis was performed for preoperative infection, location of Charcot breakdown, and post reconstruction outcomes, in patients with a minimum of 1 year follow-up period. Through bivariate analysis, presence of preoperative ulceration (p =.0499) was found to be statistically more likely in the patients with diabetes; whereas, delayed osseous union (p =.0050) and return to ambulation (p ≤.0001) was statistically more likely in patients without diabetes. The nondiabetic Charcot patients were 17.6 folds more likely to return to ambulation (odds ratio [OR] 17.6 [95% confidence interval {CI} {3.5-87.6}]), and 16.4 folds more likely to have delayed union (OR 16.4 [95% CI {1.9-139.6)]). Subanalysis compared well-controlled diabetic and nondiabetic Charcot neuroarthropathy patients for same factors. Multivariate analysis, in the subanalysis, found return to ambulation was 15.1 times likely to occur in the nondiabetic CN cohort (OR 15.1 [95% CI 1.3-175.8]) compared to the well-controlled diabetic CN cohort. [ABSTRACT FROM AUTHOR]

Equinus contracture carries 3- and 4-fold associations with diabetes and plantar foot ulceration, respectively. Percutaneous tendo-Achilles lengthening is a useful method to alleviate peak plantar pressure resulting from equinus. We aimed to evaluate the effectiveness of percutaneous tendo-Achilles lengthening and estimate the relative longevity of the approach in reducing ulcer recurrence. The medical records of patients with equinus contracture who underwent percutaneous tendo-Achilles lengthening from 2010 to 2017 were reviewed. Included patients presented with plantar ulcers and a gastroc-soleus equinus of any angle <10° of ankle dorsiflexion with the affected knee extended and flexed. Patients who received concomitant tendon lengthening procedures (including anterior tibial tendon or flexor digitorum longus) were excluded. Outcome measures included time to wound healing, time to ulcer recurrence, and development of transfer lesion. Ninety-one patients underwent percutaneous tendo-Achilles lengthening with subsequent pedal ulceration without concomitant procedures. A total of 69 (75.8%) patients had a plantar forefoot ulcer, 7 (7.7%) had midfoot ulcers, 5 (5.5%) had hindfoot ulcers, and 3 (3.3%) had ulcers in multiple locations. Seven patients received prophylactic tendo-Achilles lengthening. At a mean follow-up of 31.6 months (±26), 66 (78.6%) wounds healed at a median 12.9 weeks. A total of 29 patients (43.9%) experienced ulcer recurrence at a mean of 12 months. Twelve patients (13%) experienced a transfer lesion at a mean of 16.6 months. Tendo-Achilles lengthening can be an effective adjunctive approach to achieve wound healing and reduce long-term ulcer recurrence in patients with equinus contracture and neuropathic plantar foot ulcers. A relengthening procedure may be needed within approximately 12 months from index surgery. [ABSTRACT FROM AUTHOR]

The objective of this study is to evaluate peripheral perfusion in patients who developed plantar heel ulcerations status after transmetatarsal amputation and Achilles tendon lengthening. Peripheral perfusion was assessed via contrast angiography of the 3 crural vessels (anterior tibial, posterior tibial, and peroneal arteries), as well as intact heel blush and plantar arch. The secondary objective is to correlate the arterial flow to time to develop heel ulceration and incidence of minor and major lower-extremity amputation. Diagnostic angiography without intervention was performed on 40% of patients (4/10), and interventional angiography was performed on 60% of patients (6/10). In-line flow was present in 0% (0/10) of the peroneal arteries, 60% (6/10) of the anterior tibial arteries, and 70% (7/10) of the posterior tibial arteries. Heel angiographic contrast blush was present in 60% (6/10), and intact plantar arch was present in 60% (6/10). Patients developed heel ulcerations at a mean time of 7.6 months (range 0.7 to 41.2) postoperatively. The incidence of major lower-extremity amputation was 30% (3/10), with a mean time of 5.2 months (range 3.5 to 8.3) from time of heel wound development. No amputation occurred in 6 patients (60%). Among them, intact anterior tibial inline arterial flow was present in 3, intact posterior tibial inline arterial flow was present in 6, and heel blush was present in 5. Our results demonstrate that an open calcaneal branch of the posterior tibial artery is sufficient to heal plantar heel ulcerations to potentially increase rates of limb salvage. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the frequency of complications after an ankle fracture in patients with and without diabetes and to evaluate risk factors for nonunion. We conducted a retrospective study of 439 patients with ankle fractures (31.7% had diabetes) and followed them for 1 year or until the fracture healed. The fracture severity and determination of nonunion and Charcot arthropathy were determined from independent evaluation of radiographs by 2 members of the research team. Nonunion was defined as a fracture that did not heal within 6 months of the fracture. The majority of patients were women (67% in each group). The risk of complications was significantly higher in patients with diabetes compared with those without diabetes. The odds ratio (OR) and 95% confidence interval (CI) for nonunion was 6.5 (3.4 to 12.8); for Charcot arthropathy, 7.6 (2.3 to 21.0); for wounds, 1.8 (1.1 to 2.9); for infection, 2.8 (1.4 to 5.7); and for amputation, 6.6 (0.98 to 80.0). In the logistical regression analysis, 6 factors were associated with fracture nonunion: dialysis (7.7; 1.7 to 35.2), diabetes (3.3; 1.5 to 7.4), fracture severity (bi- and trimalleolar fractures) (4.9; 1.4 to 18.0), beta blockers (2.5; 1.1 to 5.4), steroids (3.1; 1.2 to 7.7), and infection (3.7; 1.2 to 11.3). The results of the study demonstrate the increased risk of complications after an ankle fracture among patients with diabetes, dialysis, or open fractures and those using steroids and beta blockers. Further work is needed to identify areas for risk reduction. [ABSTRACT FROM AUTHOR]

• Video-conference platforms (VCPs) have rapidly become utilized in the current COVID-19 pandemic to promote social distancing. • Radiology trainee education, as regulated by the ACGME, necessitates active learning based on image review and VCPs can facilitate and support this. • Patient protected health information and HIPAA requirements must be adhered to even with VCPs and many platforms have the appropriate security measures to comply. • Tools within the VCP permit two-way interaction, screen control/sharing, and annotation features, which enable appropriate education even in a remote setting. Technologic advances have resulted in the expansion of web-based conferencing and education. While historically video-conferencing has been used for didactic educational sessions, we present its novel use in virtual radiology read-outs in the face of the COVID-19 pandemic. Knowledge of key aspects of set-up, implementation, and possible pitfalls of video-conferencing technology in the application of virtual read-outs can help to improve the educational experience of radiology trainees and promote potential future distance learning and collaboration. [ABSTRACT FROM AUTHOR]

The aim of this study was to systematically revise the root canal configuration (RCC) literature and to investigate the root canal morphology of mandibular first premolars (Ma1Ps) of 2 populations by means of micro–computed tomographic imaging. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines including RCC randomized controlled trials and cross-sectional, cohort, comparative, validation, and evaluation studies. Furthermore, the RCC, physiological foramina, the frequency of accessory and connecting canals, and the physiological foramina morphology of 109 Ma1Ps were investigated by means of micro–computed tomographic imaging. The RCC results are described using a 4-digit system code. The most frequent RCCs observed were 1-1-1/1 (70.6%), 1-1-2/2 (7.3%), 1-2-2/2 (7.3%), and 1-2-1/1 (5.5%). Accessory canals were observed in 31.2%. Connecting canals were observed in 1-1-2/2 (4.6%), 1-2-2/2 (4.6%), 1-1-2/1 (1.8%), and 1-2-1/1 (1.8%) RCCs. Accessory foramina were observed in 52.3%; 30.3% of the Ma1Ps had 1 accessory foramen, 12.8% had 2, 2.8% had 3, 2.8% had 4, 2.8% had 5, and 0.92% had 6. The narrow and wide diameter mean of 136 physiological foramina was 0.28 mm (±0.9) and 0.37 mm (±0.11) when only 1 physiological foramen was present. This study provides detailed root canal morphology of Ma1Ps in a Swiss-German population. Within the limitations of the study, the authors recommend a final physiological foramen preparation size of instrument tip sizes 30–40; yet, such a decision should be carefully considered on an individual basis. [ABSTRACT FROM AUTHOR]

Background: Conflicting evidence exists surrounding the use of preclosure irrigation solutions in primary total joint arthroplasty (TJA). We aimed to determine the role of dilute betadine lavage in preventing early infection after primary TJA.Methods: We retrospectively reviewed primary TJAs between 2010 and 2018. Dilute betadine lavage was introduced to our practice in November 2014. We included 3513 total hip arthroplasties, 3932 total knee arthroplasties, and 1033 hip resurfacings (HRs). In group 1 (n = 5588), surgical wounds were irrigated with saline; group 2 used dilute betadine solution (n = 2890). Subanalyses using propensity matching based on known risk factors of infection-age, body mass index, American Society of Anesthesiologists grade, diabetes, and procedure-were completed.Results: There were 48 acute infections in group 1 (0.9%) and 23 in group 2 (0.8%) (P = .762). HR without betadine had the highest acute infection prevalence (P = .028). When groups in the whole cohort were propensity score-matched, group 1 had more acute infections than group 2 (P = .033). The effect of betadine was isolated to HR patients. After excluding HR cases, betadine continued to reduce the acute infection rate when compared with the no betadine group, but this was not statistically significant (0.4% vs 0.8%; P = .101). Likewise, we did not find a significant difference in total hip arthroplasty and total knee arthroplasty patients (P = .796).Conclusion: There was a decreased infection rate in the betadine group overall when groups were propensity-matched. Because the reduction in the acute infection rate was clinically significant, we feel this practice is an effective means to prevent infections. [ABSTRACT FROM AUTHOR]

The most common consequence of neuropathy is a diabetic foot ulcer, which usually occurs on the plantar surface of the foot. Split-thickness skin grafting (STSG) has been shown in numerous studies to be an effective treatment for rapid coverage of diabetic ulcers. The purpose of this study is to retrospectively examine the outcomes of STSG to the plantar foot and determine the durability of this treatment compared to non–plantar surface STSG. This is a retrospective, single-center, institutional review board approved, case-control study of all patients who received STSG to their lower extremity for chronic ulcers from November 2013 to February 2017. Patients with ulcers on the plantar surface were considered cases, and non–plantar surface ulcers were considered controls. There were 182 patients who received STSG to the lower extremity, 52 to the plantar surface foot and 130 to non–plantar surface locations. Healing at 30 days was not significantly different between plantar and nonplantar ulcers (19% versus 28%, p =.199) but did become significant at 60, 90, and 365 days (21% versus 45%, p =.003; 33% versus 49%, p =.043; 38% versus 64%, p =.002, respectively). However, time to full healing was not significantly different between plantar and nonplantar groups (18.2 ± 19.5 versus 17.4 ± 21.6 weeks, mean ± standard deviation, p =.84). Recurrence was low for both groups (17% versus 10%, respectively), and there was no significant difference between groups (p =.17). Patients with plantar surface ulcers can achieve a durable coverage/closure of their wounds with STSG. When combined with appropriate patient selection and postoperative offloading, acceptable recurrence rates can be achieved. [ABSTRACT FROM AUTHOR]

The pedicled temporoparietal fascial flap (TPFF) with a direct superficial temporal (STA) artery to middle cerebral artery (MCA) bypass is a novel combined revascularization approach for moyamoya angiopathy (MMA). With this case series, we aim to report the initial experience with pedicled TPFF combined revascularization for MMA treatment. Data from 14 consecutive patients undergoing pedicled TPFF combined revascularization for MMA between May 2016 and December 2018 were retrospectively reviewed. Patients admitted with acute ischemia or a modified Rankin Scale (mRS) score >3 were considered high risk. Mean ± standard deviation age on surgery was 41.9 ± 15.4 years. Three of 14 patients (21.4%) presented with an mRS score >3. Nine of 14 patients (64.3%) presented with ischemic stroke, 4 of whom (44.4%) had acute ischemia. Direct anastomosis patency was confirmed in all cases postoperatively. Mean hospitalization time was 13 ± 9.3 days and mean follow-up time was 14.1 ± 9.3 months. From admission to follow-up, neurologic status improved in 8 patients (57.1%) and stabilized in 6 patients (42.9%). Overall, 11/14 patients (78.6%) achieved good functional outcome (mRS score ≤2). All patients achieved some radiographic collateral development, with 5 (71.5%) graded as Matsushima A and B. Three patients developed new radiographic ischemia and 3 experienced wound complications, all in the high-risk group. The TPFF combined approach is a viable strategy for revascularization in MMA. This technique may be suboptimal in patients presenting with acute ischemia and/or mRS score >3. [ABSTRACT FROM AUTHOR]

The definitive treatment for refractory heart failure is heart transplantation (HTx). Previous literature has shown lower rates of HTx in women compared to men. However, it is unknown if the discrepancy is due to sex differences in heart failure rates versus potential sex bias in HTx candidacy referral and evaluation. We hypothesize that there are sex differences in referral and evaluation contributing to lower rates of women that undergo HTx. This was a single-center, retrospective study of adult heart failure patients referred for HTx to University of California, San Diego Health from 2012 - 2022. Patient data was collected from the electronic medical record (EMR). Categorical variables were expressed as frequency and percentage and compared with the use of either Pearson's chi-square or Fisher's exact test as appropriate. P < 0.05 was considered significant. In the evaluation of our EMR of 3.6 million patients that represent the general U.S. population, 55,506 patients were diagnosed with heart failure with 24,112 (43.4%) women and 31,394 (56.6%) men. There were 1,596 patients referred from the general community for consideration of HTx (Figure 1A). We observed a significant sex difference with less women referred than men (22.2% vs 77.8%; p < 0.001) when compared to women and men with heart failure in the general community. Following the transplant committee evaluation, we also observed a significant sex difference with less women approved for HTx compared to men (40.8% vs 48.1%; p = 0.05). In addition, we performed a subgroup analysis of 427 (101 women, 326 men) patients that were deemed ineligible for evaluation for HTx. We observed a trend towards more women being deemed ineligible for financial reasons (p = 0.10) and patient's choice (p = 0.17) compared to men (Figure 1B). We observe sex differences at different points during the evaluation process, from community referral to committee approval, that lead to lower rates of women undergoing HTx compared to men. Further studies are needed to identify specific factors contributing to lower rates of transplant in women, particularly at the level of community referrals where we observed the greatest sex discrepancy. [ABSTRACT FROM AUTHOR]

C4d immunostaining of endomyocardial biopsies (EMB) is necessary for the pathologic diagnosis of antibody-mediated rejection in heart transplant (HTx) patients. However, prior studies of C4d positive EMBs have shown contradictory findings on clinical outcomes. In this study, we examined whether C4d positive EMBs in the presence of positive donor specific antibodies (DSA) are associated with worse clinical outcomes. C4d and DSA positive HTx patients will have worse clinical outcomes compared to the three other C4d/DSA groups. This was a single center, retrospective study of endomyocardial biopsies (EMB) performed between January 2002 and February 2023 at University of California, San Diego Health. Patient data and clinical outcomes of death, cardiac allograft dysfunction (<50% LVEF), and clinically significant CAV (>CAV ISHLT grade 2) were collected. Categorical variables were expressed as frequency and percentage and compared with the use of either Pearson's chi-square or Fisher's exact test as appropriate. P < 0.05 was considered significant. A total of 6,294 EMBs from 612 adult HTx patients were analyzed. HTx patients were categorized into four groups based on C4d and DSA positivity: C4d+/DSA+ (n=31), C4d+/DSA- (n=35), C4d-/DSA+ (n=100), and C4d-/DSA- (n=386). There was no significant difference in all-cause death in the four C4d/DSA groups. However, C4d+/DSA+ patients showed significantly higher rates of cardiac death (p=0.01; Table) and cardiac allograft dysfunction (p<0.001) compared to the C4d-/DSA- group. There was no significant difference in clinical outcomes in the C4d+/DSA+ group compared to the C4d+/DSA- group in pairwise comparisons. We also did not observe any significant difference in the rate of CAV in the four C4d/DSA groups. The C4d+/DSA+ group demonstrated significantly higher rates of cardiac death and allograft dysfunction compared to the C4d-/DSA- group. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the diagnostic value of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in differentiating foot osteomyelitis (OM) from soft tissue infection (STI) in persons without diabetes. We evaluated 102 patients in a retrospective cohort study of nondiabetic patients admitted to our institution with OM (n = 51) and with STI (n = 51). Patient diagnosis was determined through bone culture and/or histopathology for OM and magnetic resonance scan and/or single-photon emission computed tomography for STI. Cutoffs for ESR and CRP to predict OM as identified by receiver operating characteristic were 45.5 mm/h and 3.45 mg/dL, respectively. The ESR cutoff demonstrated a sensitivity and specificity of 49% and 79%, while the values for CRP were 45% and 71%, respectively. The combined sensitivity and specificity for ESR and CRP were 33% and 84%. The positive and negative predictive values were 68% and 60% for ESR and 61% and 56% for CRP, respectively. In conclusion, ESR and CRP demonstrate poor sensitivity and specificity for detecting OM in the nondiabetic foot. These markers have little diagnostic utility in the nondiabetic foot. [ABSTRACT FROM AUTHOR]

Highlights • We developed a novel HA quantitative ELISA as an alternative for SRID. • The ELISA uses broadly reactive group-specific universal mAbs. • The assay is less time-consuming than the SRID assay. • The assay has good accuracy, specificity, sensitivity and reproducibility. • The assay performs better than SRID in terms of accuracy and sensitivity. Abstract Seasonal and pandemic influenza infections remain a serious public health concern. Many health authorities recommend annual vaccination as the most effective way to control influenza infection. Accordingly, regulatory guidelines ask vaccine manufacturers to determine vaccine potency at the time of release and throughout shelf-life to ensure vaccine quality. The potency of inactivated influenza vaccine is related to the quantity of hemagglutinin (HA). Since 1970s, single radial immunodiffusion (SRID) assay has been standardly used for the quantitation of HA in influenza vaccine. However, SRID is labor-intensive, inaccurate, and requires standard reference reagents that should be updated annually. Therefore, there have been extensive efforts to develop alternative potency assays. In this study, we developed and tested a new HA quantitative enzyme-linked immunosorbent assay (ELISA) using a universal monoclonal antibody that can bind to HAs from various subtypes in group 1 influenza A virus (IAV). We analyzed the conserved stalk domain of HA via a library approach to design a consensus HA antigen for group 1 IAV. The antigens were expressed as a soluble form in E. coli and were purified by Ni-affinity chromatography. When tested with variety of HAs from IAVs or influenza B viruses (IBVs), the mAbs exhibited specific binding to group 1 HAs, with potential exception to H9 subtype. Among various conditions of pH, urea, and reducing agents, pretreatment of HA at low pH exposing the conserved stalk domain was crucially important for optimal ELISA performance. Calibration curves for various HAs were generated to determine accuracy, specificity, sensitivity, and linear dynamic range. The ELISA method shows high sensitivity and accuracy compared with the SRID assay. The HA group specific universal mAbs against the consensus stalk domain of HA are conducive to establishing an ELISA-based standard procedure for the quantitation of HA antigens for annual vaccination against influenza infection. [ABSTRACT FROM AUTHOR]

ABSTRACT Heel ulcers have a significant impact on lower extremity morbidity and confer a high risk for major amputations. Although there are many conservative treatment options, once calcaneal osteomyelitis occurs or a heel ulcer becomes chronic or recalcitrant, more invasive management is required. The partial calcanectomy is a surgical solution that can address both pathologies—the ulceration and the infected bone. The conventional partial calcanectomy, however, does not ensure complete soft tissue closure. Often, closure under tension is required for primary closure of the soft tissue deficit or the wound must be closed by secondary intention. This process occurs, in part, when the proportion of bone resected is insufficient in relation to the size of the wound. Closure under tension increases the possibility of dehiscence and subsequent postoperative surgical site complications that lead to the same risks for major amputation as the index heel ulcer. This article introduces and describes a novel modification to the conventional partial calcanectomy and addresses these aforementioned concerns. The vertical contour calcanectomy incorporates improvements to an already accepted limb salvage technique. The purpose of this article was to describe the indications, contraindications, intraoperative technique and postoperative management of the vertical contour calcanectomy for patients who present with heel ulcers in the limb salvage setting. [ABSTRACT FROM AUTHOR]

Abstract The challenge for the pediatric emergency medicine provider is to identify cardiac emergencies even when the chief complaint is not clearly cardiac. An additional challenge is to consider whether subspecialty consultation is required and, if so, to determine in what capacity and with what urgency. In this article, we review guiding principles surrounding subspecialty consultation in pediatrics and examine factors in all phases of a consultation from the perspective of both the pediatric emergency medicine provider and the pediatric cardiologist. In the Preliminary Phase , we discuss considerations surrounding whether a consult should be called and introduce the categories of "FYI" and "Curbside" calls. In the Action Phase , we review different circumstances appropriate for traditional (in-person) and telemedicine consultations. In the Aftercare Phase , we summarize the responsibilities of each party, emphasizing the need to ascertain appropriate access to effective follow-up care. We conclude by recommending that future efforts should be focused on collaboration between EDs and local pediatric cardiology groups to devise guidelines or clinical reference documents in regard to consultation expectations and parameters, with a suggested starting point included. [ABSTRACT FROM AUTHOR]