The classification of type 2 diabetes and prediabetes does not consider heterogeneity in the pathophysiology of glucose dysregulation. Here we show that prediabetes is characterized by metabolic heterogeneity, and that metabolic subphenotypes can be predicted by the shape of the glucose curve measured via a continuous glucose monitor (CGM) during standardized oral glucose-tolerance tests (OGTTs) performed in at-home settings. Gold-standard metabolic tests in 32 individuals with early glucose dysregulation revealed dominant or co-dominant subphenotypes (muscle or hepatic insulin-resistance phenotypes in 34% of the individuals, and β-cell-dysfunction or impaired-incretin-action phenotypes in 40% of them). Machine-learning models trained with glucose time series from OGTTs from the 32 individuals predicted the subphenotypes with areas under the curve (AUCs) of 95% for muscle insulin resistance, 89% for β-cell deficiency and 88% for impaired incretin action. With CGM-generated glucose curves obtained during at-home OGTTs, the models predicted the muscle-insulin-resistance and β-cell-deficiency subphenotypes of 29 individuals with AUCs of 88% and 84%, respectively. At-home identification of metabolic subphenotypes via a CGM may aid the risk stratification of individuals with early glucose dysregulation.

Elevated postprandial glycemic responses (PPGRs) are associated with type 2 diabetes and cardiovascular disease. PPGRs to the same foods have been shown to vary between individuals, but systematic characterization of the underlying physiologic and molecular basis is lacking. We measured PPGRs using continuous glucose monitoring in 55 well-phenotyped participants challenged with seven different standard carbohydrate meals administered in replicate. We also examined whether preloading a rice meal with fiber, protein or fat (‘mitigators’) altered PPGRs. We performed gold-standard metabolic tests and multi-omics profiling to examine the physiologic and molecular basis for interindividual PPGR differences. Overall, rice was the most glucose-elevating carbohydrate meal, but there was considerable interindividual variability. Individuals with the highest PPGR to potatoes (potato-spikers) were more insulin resistant and had lower beta cell function, whereas grape-spikers were more insulin sensitive. Rice-spikers were more likely to be Asian individuals, and bread-spikers had higher blood pressure. Mitigators were less effective in reducing PPGRs in insulin-resistant as compared to insulin-sensitive participants. Multi-omics signatures of PPGR and metabolic phenotypes were discovered, including insulin-resistance-associated triglycerides, hypertension-associated metabolites and PPGR-associated microbiome pathways. These results demonstrate interindividual variability in PPGRs to carbohydrate meals and mitigators and their association with metabolic and molecular profiles.

Knee dislocations (KD) and multiligamentous knee injuries (MLKI) are challenging injuries to manage due to the high incidence of associated neurovascular compromise, extensive peri-articular soft-tissue trauma, and long-term functional deficits. Knee-spanning external fixation (KSEF) is occasionally utilized in the acute management of these injuries with the aim of maintaining alignment, protecting vascular repairs, allowing soft-tissue recovery prior to definitive treatment, and protecting freshly reconstructed or repaired ligaments. Despite its use in 5% of MLKIs and up to 50% of KDs, the clinical indications, outcomes, and complications associated with KSEF in the setting of KD/MLKI remain incompletely defined. Furthermore, KD/MLKI treatment algorithms incorporating decision-making related to KSEF application are limited both institutionally and within the literature. Thus, the purpose of this study was to consolidate the existing evidence related to the use of KSEF in the setting of KD/MLKI to support clinical decision-making and identify avenues for future investigation. Following a narrative review of the literature, the identified indications for KSEF in the setting of KD/MLKI were vascular injury, knee fracture-dislocation, extensive soft-tissue injury, persistent instability following reduction, open KDs, and when bracing is not feasible due to patient factors such as morbid obesity. Both rigid and hinged KSEF constructs have been described, with hinged fixators potentially permitting early motion while providing joint stability. Reported complications of KSEF include arthrofibrosis, infection, heterotopic ossification, and compartment syndrome, though available data are primarily retrospective and heterogeneous. Other topics that have been addressed in the literature include biomechanics, cost, magnetic resonance imaging (MRI) compatibility, and psychological impact. However, further research is needed to clarify its specific role, define standardized indications, and compare outcomes with non-invasive or alternative fixation and immobilization strategies. Plain Language Summary: Knee dislocations and multiple ligament knee injuries are serious injuries that can cause damage to blood vessels, nerves, and soft tissues around the knee, leading to long-term challenges with movement. Doctors sometimes use a device called a knee-spanning external fixator to treat these injuries, which is a metal frame that surgeons place outside of the leg to hold the knee stable This article summarizes what doctors and researchers currently know about knee-spanning external fixators, including their risks and benefits, and explains why more research is needed to guide treatment decisions related to the use of these devices in the management of severe knee injuries. This device is mainly used when the knee is too unstable for a brace, when there is a blood vessel injury, when the skin around the knee is severely damaged, and when the patient has multiple other injuries that need to be managed before their knee injury. While knee-spanning external fixators can help protect the knee and allow it to heal, they also carry several risks like stiffness, infections where the pins enter the skin, unwanted bone growth in the knee, and excessive pressure build-up within the leg. There are also psychological and cost-related concerns associated with the use of these devices. Despite being used frequently, doctors and researchers have not reached a clear agreement about exactly when to use or avoid these devices.

Purpose: While rigid knee‐spanning external fixation is more commonly utilized in the treatment of complex knee injuries compared to hinged external fixation (HEF), HEF has the added benefit of providing stability while also permitting early controlled range of motion. However, there is limited existing literature on the indications for HEF of the knee. The aim of this study was to review the clinical indications for HEF in the management of acute and chronic knee dislocations (KD), tibiofemoral subluxations and knee fracture‐dislocations.Methods: Five databases, including PubMed, CINAHL, Cochrane, Scopus and SPORTDiscus, were systematically searched. Included studies were those that involved comparative or non‐comparative evaluation of patients with an HEF applied for an acute or chronic KD, tibiofemoral subluxation or knee fracture‐dislocation.Results: Fourteen studies ranging from 1998 to 2023 met inclusion criteria, with a total of 184 knees treated with HEF for an acute or chronic KD, tibiofemoral subluxation, or knee fracture‐dislocation. The most common primary indication for HEF was acute or chronic KD. The most common secondary indications included combined osseous and ligamentous deficiency, associated vascular or soft‐tissue injury, status post extensive capsular release for arthrofibrosis, and associated extensor mechanism disruption.Conclusion: While uncommon, HEF is a valuable option in the treatment of complex knee injuries where both stability and controlled mobilization are essential. Due to limitations in the available evidence, further high‐quality research is needed to establish guidelines for the utilization of HEF about the knee.Level of Evidence: Level IV.

An understanding of the embryonic and fetal formation of the knee can help elucidate the relationships between the various structures and clinical conditions. While there have been studies published on the steps of knee development by sectioning human embryos and fetuses, the goal of this review is to consolidate these findings and images into one cohesive work. The timing and appearance of the structures in the knee are outlined with a focus on the cruciate and meniscofemoral ligaments (MFLs). In particular, the posterior cruciate ligament is emphasized with its relationship to other intraarticular structures and congenital anomalies that may arise. The steps of embryological development are outlined by the 23 stages of Carnegie embryonic staging system, which are distinguished by morphological criteria seen on histology of embryo sections. These images highlight the mesenchymal tissue within the interzone of the knee that form the primitive cruciate ligaments and menisci and the subsequent development of the cavitations within the knee that start to give it an appearance similar to that of an adult knee. The steps of fetal development are outlined by the weeks of development with the histological images showing the development of articulations between structures. This review paper consolidates various sources throughout the literature to outline the embryological and fetal appearance and relationship of intraarticular structures in the knee, such as the cruciate and MFLs, and how their altered development may contribute to the congenital anomalies and clinical conditions that may arise.

External fixation is widely used in trauma care for managing bone and soft tissue injuries. These devices are often associated with psychological challenges and are often not followed up with sufficient psychological support for the patient. The specific psychological impact of external fixation following traumatic injuries remains underexplored. This scoping review aimed to synthesize the current literature on the psychological impact of external fixation in trauma patients. A systematic search of CINAHL, Cochrane Library, PsycInfo, PubMed, Scopus, Google Scholar, and EBSCO identified ten studies (2006–2024), from the USA, Europe, Asia, and Oceania to be included based on inclusion criteria of using the device for traumatic injuries (excluding limb lengthening procedures) and assessing psychological outcomes using validated tools. Data extracted included injury type, fixator application, survey type, and mental health outcomes. Common measures included HADS, SF-36/SF-12, PedsQL, CRIES-13, EQ-5D-5L, and patient-reported questionnaires. The findings showed that elevated psychological distress was greatest during early recovery (~1 month). Body image concerns were frequently reported with the fixator in place; however, partial recovery of mental health scores was seen by 12–24 months. These findings emphasize the need for additional research and a greater integration of mental health resources in trauma care protocols involving external fixation.