Citations

Abstract Alpha‐synuclein (αsyn) aggregates are pathological features of several neurodegenerative conditions including Parkinson disease (PD), dementia with Lewy bodies, and multiple system atrophy (MSA). Accumulating evidence suggests that mitochondrial dysfunction and impairments of the autophagic‐lysosomal system can contribute to the deposition of αsyn, which in turn may interfere with health and function of these organelles in a potentially vicious cycle. Here we investigated a potential convergence of αsyn with the PINK1‐PRKN‐mediated mitochondrial autophagy pathway in cell models, αsyn transgenic mice, and human autopsy brain. PINK1 and PRKN identify and selectively label damaged mitochondria with phosphorylated ubiquitin (pS65‐Ub) to mark them for degradation (mitophagy). We found that disease‐causing multiplications of αsyn resulted in accumulation of the ubiquitin ligase PRKN in cells. This effect could be normalized by starvation‐induced autophagy activation and by CRISPR/Cas9‐mediated αsyn knockout. Upon acute mitochondrial damage, the increased levels of PRKN protein contributed to an enhanced pS65‐Ub response. We further confirmed increased pS65‐Ub‐immunopositive signals in mouse brain with αsyn overexpression and in postmortem human disease brain. Of note, increased pS65‐Ub was associated with neuronal Lewy body‐type αsyn pathology, but not glial cytoplasmic inclusions of αsyn as seen in MSA. While our results add another layer of complexity to the crosstalk between αsyn and the PINK1‐PRKN pathway, distinct mechanisms may underlie in cells and brain tissue despite similar outcomes. Notwithstanding, our finding suggests that pS65‐Ub may be useful as a biomarker to discriminate different synucleinopathies and may serve as a potential therapeutic target for Lewy body disease.

Background Thromboelastography is a viscoelastic test with multiple potential advantages over conventional coagulation tests in various disease states. Thromboelastography rapidly provides qualitative and quantitative information related to a patient’s coagulation status. Objective To describe recent studies of the use of thromboelastography in various clinical states and how thromboelastography is used in coagulation management. Methods A literature review using the MEDLINE and PubMed databases was conducted. The updated methodology for integrated reviews by Whittemore and Knafl was followed. Coauthors evaluated separate areas that were independently reviewed by other coauthors to ensure appropriateness for inclusion. Results The use of thromboelastography for various clinical conditions with challenging hemostatic profiles has increased. This integrative review covers the use of thromboelastography in patients with trauma, medication-induced coagulopathy, acute and chronic liver failure, and cardiothoracic surgery. Potential future directions are also discussed. Discussion Thromboelastography has numerous potential benefits over conventional coagulation tests for assessing coagulation status in patients in various clinical states. Nurses can support clinical decisions to use the most appropriate test for their patients. Conclusions Each team member should be involved in assessing the usefulness of thromboelastography. Critical care nurses and the multidisciplinary team must identify patients in whom its use is warranted, interpret the results, and provide appropriate interventions in response to the results and clinical status of the patient.

AimsKnowledge on total knee arthroplasties (TKAs) in patients with a history of poliomyelitis is limited. This study compared implant survivorship and clinical outcomes among affected and unaffected limbs in patients with sequelae of poliomyelitis undergoing TKAs.MethodsA retrospective review of our total joint registry identified 94 patients with post-polio syndrome undergoing 116 primary TKAs between January 2000 and December 2019. The mean age was 70 years (33 to 86) with 56% males (n = 65) and a mean BMI of 31 kg/m2 (18 to 49). Rotating hinge TKAs were used in 14 of 63 affected limbs (22%), but not in any of the 53 unaffected limbs. Kaplan-Meier survivorship analyses were completed. The mean follow-up was eight years (2 to 19).ResultsThe ten-year survivorship free from revision was 91% (95% confidence interval (CI) 81 to 100) in affected and 84% (95% CI 68 to 100) in unaffected limbs. There were six revisions in affected limbs: three for periprosthetic femoral fractures and one each for periprosthetic joint infection (PJI), patellar clunk syndrome, and instability. Unaffected limbs were revised in four cases: two for instability and one each for PJI and tibial component loosening. The ten-year survivorship free from any reoperation was 86% (95% CI 75 to 97) and 80% (95% CI 64 to 99) in affected and unaffected limbs, respectively. There were three additional reoperations among affected and two in unaffected limbs. There were 12 nonoperative complications, including four periprosthetic fractures. Arthrofibrosis occurred in five affected (8%) and two unaffected limbs (4%). Postoperative range of motion decreased with 31% achieving less than 90° knee flexion by five years.ConclusionTKAs in post-polio patients are complex cases associated with instability, and one in four require constraint on the affected side. Periprosthetic fracture was the main mode of failure. Arthrofibrosis rates were high and twice as frequent in affected limbs.Cite this article: Bone Joint J 2023;105-B(6):635–640.

AimsNonagenarians (aged 90 to 99 years) have experienced the fastest percent decile population growth in the USA recently, with a consequent increase in the prevalence of nonagenarians living with joint arthroplasties. As such, the number of revision total hip arthroplasties (THAs) and total knee arthroplasties (TKAs) in nonagenarians is expected to increase. We aimed to determine the mortality rate, implant survivorship, and complications of nonagenarians undergoing aseptic revision THAs and revision TKAs.MethodsOur institutional total joint registry was used to identify 96 nonagenarians who underwent 97 aseptic revisions (78 hips and 19 knees) between 1997 and 2018. The most common indications were aseptic loosening and periprosthetic fracture for both revision THAs and revision TKAs. Mean age at revision was 92 years (90 to 98), mean BMI was 27 kg/m2 (16 to 47), and 67% (n = 65) were female. Mean time between primary and revision was 18 years (SD 9). Kaplan-Meier survival was used for patient mortality, and compared to age- and sex-matched control populations. Reoperation risk was assessed using cumulative incidence with death as a competing risk. Mean follow-up was five years.ResultsMortality rates were 9%, 18%, 26%, and 62% at 90 days, one year, two years, and five years, respectively, but similar to control populations. There were 43 surgical complications and five reoperations, resulting in a cumulative incidence of reoperation of 4% at five years. Medical complications were common, with a cumulative incidence of 65% at 90 days. Revisions for periprosthetic fractures were associated with higher mortality and higher 90-day risk of medical complications compared to revisions for aseptic loosening.ConclusionContemporary revision THAs and TKAs appeared to be relatively safe in selected nonagenarians managed with multidisciplinary teams. Cause of revision affected morbidity and mortality risks. While early medical and surgical complications were frequent, they seldom resulted in reoperation.Cite this article: Bone Joint J 2023;105-B(6):649–656.

AimsThe benefit of MRI in the preoperative assessment of scaphoid proximal fragment vascularity remains controversial. The purpose of this study is to compare preoperative MRI findings to intraoperative bleeding of the proximal scaphoid.MethodsA retrospective review of 102 patients who underwent surgery for scaphoid nonunion between January 2000 and December 2020 at a single institution were identified. Inclusion criteria were: isolated scaphoid nonunion; preoperative MRI assessing the proximal fragment vascularity; and operative details of the vascularity of the proximal fragment with the tourniquet deflated. MRI results and intraoperative findings were dichotomized as either ‘yes’ or ‘no’ for the presence of vascularity. A four-fold contingency table was used to analyze the utility of preoperative MRI with 95% confidence intervals. Relative risk was calculated for subgroups to analyze the association between variables and MRI accuracy.ResultsPreoperative MRI identified 55 proximal scaphoid fragments with ischaemia and 47 with vascularized proximal fragments. After the proximal fragment was prepared, the tourniquet was deflated and assessed for bleeding; 63 proximal fragments had no bleeding and 39 demonstrated bleeding. MRI was not reliable or accurate in the assessment of proximal fragment vascularity when compared with intraoperative assessment of bleeding. No patient or MRI factors were identified to have a statistical impact on MRI accuracy.ConclusionCurrent preoperative MRI protocols and diagnostic criteria do not provide a high degree of correlation with observed intraoperative assessment of proximal fragment bleeding. While preoperative MRI may assist in surgical planning, intraoperative assessment remains the best means for assessing proximal fragment vascularity in scaphoid nonunion. Future efforts should focus on the development of objective measures of osseous blood flow that may be performed intraoperatively.Cite this article: Bone Joint J 2023;105-B(6):657–662.

AbstractAn increasing number of machine learning applications are being developed and applied to digital pathology, including hematopathology. The goal of these modern computerized tools is often to support diagnostic workflows by extracting and summarizing information from multiple data sources, including digital images of human tissue. Hematopathology is inherently multimodal and can serve as an ideal case study for machine learning applications. However, hematopathology also poses unique challenges compared to other pathology subspecialities when applying machine learning approaches. By modeling the pathologist workflow and thinking process, machine learning algorithms may be designed to address practical and tangible problems in hematopathology. In this article, we discuss the current trends in machine learning in hematopathology. We review currently available machine learning enabled medical devices supporting hematopathology workflows. We then explore current machine learning research trends of the field with a focus on bone marrow cytology and histopathology, and how adoption of new machine learning tools may be enabled through the transition to digital pathology.

Purpose: To describe new histological findings involving the inner retina in birdshot chorioretinopathy. Methods: Evaluation of the inner retinal pathology of the eye of a patient with bilateral birdshot chorioretinopathy who underwent enucleation for a unilateral ciliochoroidal melanoma. Results: Histopathological sections showed focal perivascular lymphocytic infiltration at the optic nerve head that extended into the adjacent inner retina, mainly involving the ganglion and nerve fiber layers. Conclusion: We have previously shown that birdshot chorioretinopathy has multiple foci of lymphocytes in the choroid. This is the first report that demonstrates lymphocytic infiltration of the inner retinal layers. This may lead to the bipolar and Müller cell dysfunction that ultimately results in an electronegative electroretinogram.

Background: The authors examined whether ultrasound sensitivity, specificity, and accuracy in identifying intact repairs or flexor tendon gapping after zone 2 repair are affected by the number of suture strands crossing the repair or gap or imaging modality (static versus dynamic). Methods: A total of 144 fresh-frozen cadaveric digits (thumbs excluded) were randomized to either an intact repair (0-mm gap) or simulated failed repair (4-mm gap), as well as to either a two- or eight-strand locked-cruciate repair of a zone 2 flexor digitorum profundus tendon laceration using 4-0 Fiberwire. Examinations were performed by a blinded musculoskeletal ultrasonographer in static and dynamic modes using an 18-MHz transducer. Gaps were remeasured after scanning, and the final gap width recorded. McNemar exact test was used to determine whether there were differences in sensitivity, specificity, and accuracy affected by modality (static versus dynamic), and chi-square test was used to compare sensitivity, specificity, and accuracy between number of strands (two versus eight) crossing the intact repair or repair gap (≥4 mm). Results: Sensitivity, specificity, and accuracy improved with increased number of suture strands crossing the repair or gap (eight versus two), irrespective of modality (static versus dynamic), and dynamic compared with static scanning modes, irrespective of number of suture strands crossing the repair or gap site. Conclusions: The most sensitive and accurate means of assessing flexor tendon repair integrity and gapping were seen using the dynamic scanning mode. Increased number of suture strands did not negatively affect sensitivity, specificity, or accuracy, regardless of scanning mode (dynamic or static).