Foot Osteomyelitis Location and Rates of Primary or Secondary Major Amputations in Patients With Diabetes

BACKGROUND Diabetic foot osteomyelitis (DFO) often leads to amputations in the lower extremity. Data on the influence of the initial anatomical DFO localization on ultimate major amputation are limited. METHODS In this retrospective analysis, 583 amputation episodes in 344 patients (78 females, 266 males) were analyzed. All received a form of amputation in combination with antibiotic therapy. A multivariate logistic regression analysis with the primary outcome "major amputation" defined as an amputation above the ankle joint was performed. The association of risk factors including location of DFO, coronary artery disease, peripheral artery disease, neuropathy, nephropathy, and Charcot neuro-osteoarthropathy was analyzed. RESULTS Among 583 episodes, DFO was located in the forefoot in 512 (87.8%), in the midfoot in 43 (7.4%), and in the hindfoot in 28 episodes (4.8%). Overall, 53 of 63 (84.1%) major amputations were performed because of DFO in the setting of peripheral artery disease as primary indication. Overall, limb loss occurred in 6.1% (31/512) of forefoot, 20.9% (9/43) of midfoot, and 46.4% (13/28) of hindfoot DFO. Among these, 22 (41.5%) were performed as the primary treatment, whereas 31 (58.5%) followed previously failed minor amputations. Among this latter group of secondary major amputations, the DFO was localized to the forefoot in 23 of 583 (3.9%), the midfoot in 4 of 583 (0.7%) and the hindfoot in 4 of 583 (0.7%). In multivariate logistic regression analysis, initial hindfoot localization was a significant factor (P < .05), whereas peripheral artery disease, smoking, and a midfoot DFO were not found to be risk factors. CONCLUSION In our retrospective series, the frequency of limb loss in DFO increased with more proximal initial foot DFO lesions, with almost half of patients losing their limbs with a hindfoot DFO. LEVEL OF EVIDENCE Level IV, retrospective cohort study

Investigation of subtle Lisfranc injuries using weight-bearing computed tomography

Introduction: Lisfranc ligamentous injuries are common yet remain a diagnostic challenge. Automated analysis of weight-bearing computed tomography (WBCT) images has been investigated to diagnose various pathologies. However, it has not been studied for Lisfranc ligament injuries. The objective of the study was to examine whether automated WBCT analysis could demonstrate diagnostic utility for these injuries. Methods: Serial sectioning of Lisfranc complex ligaments was conducted on 24 cadaveric limbs to simulate Lisfranc injuries. WBCT images were collected at each dissection condition under three loading conditions. Images were automatically segmented, and automated measures of specific angles and distances in the midfoot were calculated using digitally reconstructed radiographs. These were analyzed using repeated measures ANOVA and paired T-tests to identify significant differences between dissections at each loading condition. Results: Overall, minimal differences between dissection conditions were observed in automatically generated measures. Differences in axial angles of the metatarsals in severe dissections were observed, and there were fewer differences in angular measures across dissection conditions in fully loaded than unloaded conditions. Conclusions: Automated analysis of WBCT images may indicate severe Lisfranc ligamentous injury but is insufficient to diagnose ligament injuries without full capsule disruption. This lack of injury markers may be due to the imaging conditions, automated analysis, or biomechanics of Lisfranc injuries. More alignment differences were seen under unloaded conditions, suggesting that weight-bearing imaging may not be appropriate for this injury. Overall, automated analysis shows only minimal changes in alignment measures, and additional study is necessary to improve diagnostic tools for Lisfranc injuries. Evidence Level V; Mechanism-based reasoning

Osteotomies around the knee alter alignment of the ankle and hindfoot: a systematic review of biomechanical and clinical studies

Purpose: Emerging reports suggest an important involvement of the ankle/hindfoot alignment in the outcome of knee osteotomy; however, a comprehensive overview is currently not available. Therefore, we systematically reviewed all studies investigating biomechanical and clinical outcomes related to the ankle/hindfoot following knee osteotomies. Methods: A systematic literature search was conducted on PubMed, Web of Science, EMBASE and Cochrane Library according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on international prospective register of systematic reviews (PROSPERO) (CRD42021277189). Combining knee osteotomy and ankle/hindfoot alignment, all biomechanical and clinical studies were included. Studies investigating knee osteotomy in conjunction with total knee arthroplasty and case reports were excluded. The QUality Appraisal for Cadaveric Studies (QUACS) scale and Methodological Index for Non-Randomized Studies (MINORS) scores were used for quality assessment. Results: Out of 3554 hits, 18 studies were confirmed eligible, including 770 subjects. The minority of studies (n = 3) assessed both high tibial- and distal femoral osteotomy. Following knee osteotomy, the mean tibiotalar contact pressure decreased (n = 4) except in the presence of a rigid subtalar joint (n = 1) or a talar tilt deformity (n = 1). Patient symptoms and/or radiographic alignment at the level of the ankle/hindfoot improved after knee osteotomy (n = 13). However, factors interfering with an optimal outcome were a small preoperative lateral distal tibia angle, a small hip–knee–ankle axis (HKA) angle, a large HKA correction (>14.5°) and a preexistent hindfoot deformity (>15.9°). Conclusions: Osteotomies to correct knee deformity alter biomechanical and clinical outcomes at the level of the ankle/hindfoot. In general, these changes were beneficial, but several parameters were identified in association with deterioration of ankle/hindfoot symptoms following knee osteotomy

Multi-level multi-domain statistical shape model of the subtalar, talonavicular, and calcaneocuboid joints

Traditionally, two-dimensional conventional radiographs have been the primary tool to measure the complex morphology of the foot and ankle. However, the subtalar, talonavicular, and calcaneocuboid joints are challenging to assess due to their bone morphology and locations within the ankle. Weightbearing computed tomography is a novel high-resolution volumetric imaging mechanism that allows detailed generation of 3D bone reconstructions. This study aimed to develop a multi-domain statistical shape model to assess morphologic and alignment variation of the subtalar, talonavicular, and calcaneocuboid joints across an asymptomatic population and calculate 3D joint measurements in a consistent weightbearing position. Specific joint measurements included joint space distance, congruence, and coverage. Noteworthy anatomical variation predominantly included the talus and calcaneus, specifically an inverse relationship regarding talar dome heightening and calcaneal shortening. While there was minimal navicular and cuboid shape variation, there were alignment variations within these joints; the most notable is the rotational aspect about the anterior-posterior axis. This study also found that multi-domain modeling may be able to predict joint space distance measurements within a population. Additionally, variation across a population of these four bones may be driven far more by morphology than by alignment variation based on all three joint measurements. These data are beneficial in furthering our understanding of joint-level morphology and alignment variants to guide advancements in ankle joint pathological care and operative treatments

Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study

This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4–methylenedioxy­methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence

A multiplexed cell-free assay in double emulsion droplets

We introduce a novel on-chip assay, performed in water-in-oil-in-water double emulsions, that uses cell-free protein synthesis and artificial liposomes for the screening of membrane disrupting toxin DNA libraries according to their antimicrobial activity and host membrane safety. Our method represents a unique approach to the selection and potentially directed evolution of membrane-disrupting toxins

Subtalar Joint Alignment in Ankle Osteoarthritis

Category: Ankle Arthritis, Hindfoot Introduction/Purpose: The influence of the subtalar joint on the evolution of ankle joint osteoarthritis is still a matter of debate. Although subtalar joint compensation of deformities above the ankle joint was proposed until mid-stage of ankle osteoarthritis, the evidence of this assumption is weak. In this study, we investigated the subtalar joint alignment in different stages of ankle joint osteoarthritis using weightbearing CT scans. The influence of the tibio-talar tilt and presence of subtalar joint osteoarthritis was additionally assessed. We hypothesized, that the subtalar joint compensates for deformities above the ankle joint in early- to mid-stage of ankle osteoarthritis. We also hypothesized, that subtalar joint compensation increases with a pronounced tibio-talar tilt and decreases with the presence of subtalar joint osteoarthritis. Methods: We included patients with ankle joint osteoarthritis treated in our institution from January 2013 to April 2016. A control group of 28 patients was additionally assessed. Varus and valgus ankles were subdivided according to the modified Takakura classification, the tilt of the talus in the ankle mortise and stage of subtalar joint osteoarthritis. The type of ankle osteoarthritis was diagnosed on a plain weightbearing anterior to posterior radiograph of the ankle. The medial distal tibial angle (TAS) and the angle between the tibial shaft and the surface of the talar dome (TTS) were measured. The subtalar joint alignment was assessed using weightbearing CT scans. Two angles were assessed: The subtalar inclination angle (SIA) was measured to investigate the subtalar compensation. For assessment of the morphology of the talus, the inftal-subtal angle (ISA) was determined. Results: This analysis showed significant differences of the subtalar inclination between varus feet and the controls (SIA, P=.001). Regarding the talar morphology, significant differences were found between varus/ valgus feet and the controls (ISA, P=.001 and .036, respectively). No significant differences of the subtalar joint inclination and talar morphology could be identified comparing different stages of ankle joint osteoarthritis inside the varus or valgus group. No relationship between the tilt of the talus in the ankle joint mortise and the subtalar joint inclination or talar morphology was identified. Neither presence nor absence of subtalar joint osteoarthritis influenced the subtalar joint inclination and talar morphology. Conclusion: Varus ankles compensate in the subtalar joint for deformities above the ankle joint. Compensation had no influence on the stage of ankle osteoarthritis, extent of the tibio-talar tilt and stage of subtalar joint osteoarthritis. Consequently, the progression of ankle joint osteoarthritis is more depended on the supramalleolar alignment and integrity of the periarticular structures (i.e. ligaments and tendons) than on the osseous alignment of the subtalar joint