Citations

ABSTRACT Despite ocular adverse events from immune checkpoint inhibitors being uncommon, they are still important complications to be aware of. We present the case of metastatic melanoma on ipilimumab/nivolumab in a patient who developed immunotherapy complications with delayed diagnosis because the only presenting symptom was unilateral ptosis. We reviewed the literature for relevant and important ocular and neurological complications of immune checkpoint inhibitors.

Abstract Dysfunctional liver regeneration following surgical resection remains a major cause of postoperative mortality and has no therapeutic options. Without targeted therapies, the current treatment paradigm relies on supportive therapy until homeostasis can be achieved. Pharmacologic acceleration of regeneration represents an alternative therapeutic avenue. Therefore, we aimed to generate a small molecule inhibitor that could accelerate liver regeneration with an emphasis on diseased models, which represent a significant portion of patients who require surgical resection and are often not studied. Utilizing a clinically approved small molecule inhibitor as a parent compound, standard medicinal chemistry approaches were utilized to generate a small molecule inhibitor targeting serine/threonine kinase 4/3 (MST1/2) with reduced off-target effects. This compound, mCLC846, was then applied to preclinical models of murine partial hepatectomy, which included models of diet-induced metabolic dysfunction-associated steatohepatitis (MASH). mCLC846 demonstrated on target inhibition of MST1/2 and reduced epidermal growth factor receptor inhibition. The inhibitory effects resulted in restored pancreatic beta-cell function and survival under diabetogenic conditions. Liver-specific cell-line exposure resulted in Yes-associated protein activation. Oral delivery of mCLC846 perioperatively resulted in accelerated murine liver regeneration and improved survival in diet-induced MASH models. Bulk transcriptional analysis of regenerating liver remnants suggested that mCLC846 enhanced the normal regenerative pathways and induced them following liver resection. Overall, pharmacological acceleration of liver regeneration with mCLC846 was feasible, had an acceptable therapeutic index, and provided a survival benefit in models of diet-induced MASH.

Abstract We studied patients diagnosed with aspergillosis based on positive bronchoalveolar lavage (BAL) Aspergillus galactomannan (GM) who had follow-up BAL sampling within 180 days. GM trend and clinical outcome were concordant in only 60% (30/50). While useful for the initial diagnosis, BAL GM trending does not always correlate with treatment response.

AbstractIntroductionThis case describes passenger lymphocyte syndrome (PLS) generating human platelet antigen 1a (HPA‐1a) alloantibodies against the recipient's platelets after liver transplant. Given the rarity of PLS, especially in liver transplant with HPA‐1a alloantibodies, disease course and management options are poorly described.MethodsThe patient had cirrhosis secondary to nonalcoholic steatohepatitis complicated by hepatocellular carcinoma, encephalopathy, and severe ascites. The model for end‐stage liver disease (MELD) score was 15 at presentation. The patient developed hepatic artery thrombosis after an orthotopic liver transplant and was relisted for transplant with a MELD score of 40. The patient received a hepatitis C virus antibody positive, hepatitis C virus nucleic amplification test positive donor liver on postoperative day (POD) 7 after first transplant. On POD 7 after the second transplant, the patient developed profound thrombocytopenia refractory to platelet infusion. They were found to have serum antibody to HPA‐1a based upon serum platelet alloantibody testing. The donor was later found to be negative for HPA‐1a by genetic testing. However, the patient's native platelets were HPA‐1a positive. The patient was diagnosed with PLS.ResultsThe patient's treatment course included 57 units of platelets transfused, emergency splenectomy, rituximab, plasma exchange, intravenous immunoglobulin (IVIG), eltrombopag, romiplostim, and efgartigimod.DiscussionThe synergistic effect of efgartigimod with eltrombopag and romiplostim most likely resolved the patient's thrombocytopenia. This case represents a novel use of efgartigimod in the treatment of passenger lymphocyte syndrome following liver transplant.

AbstractDeep learning is a subset of artificial intelligence (AI) with enormous potential to transform orthopaedic surgery. As has already become evident with the deployment of Large Language Models (LLMs) like ChatGPT (OpenAI Inc.), deep learning can rapidly enter clinical and surgical practices. As such, it is imperative that orthopaedic surgeons acquire a deeper understanding of the technical terminology, capabilities and limitations associated with deep learning models. The focus of this series thus far has been providing surgeons with an overview of the steps needed to implement a deep learning‐based pipeline, emphasizing some of the important technical details for surgeons to understand as they encounter, evaluate or lead deep learning projects. However, this series would be remiss without providing practical examples of how deep learning models have begun to be deployed and highlighting the areas where the authors feel deep learning may have the most profound potential. While computer vision applications of deep learning were the focus of Parts I and II, due to the enormous impact that natural language processing (NLP) has had in recent months, NLP‐based deep learning models are also discussed in this final part of the series. In this review, three applications that the authors believe can be impacted the most by deep learning but with which many surgeons may not be familiar are discussed: (1) registry construction, (2) diagnostic AI and (3) data privacy. Deep learning‐based registry construction will be essential for the development of more impactful clinical applications, with diagnostic AI being one of those applications likely to augment clinical decision‐making in the near future. As the applications of deep learning continue to grow, the protection of patient information will become increasingly essential; as such, applications of deep learning to enhance data privacy are likely to become more important than ever before.Level of Evidence: Level IV.

Abstract The neonatal period is a peak time for the presentation of genetic disorders that can be diagnosed using whole genome sequencing (WGS). While any one genetic disorder is individually rare, they collectively contribute to significant morbidity, mortality, and health-care costs. As the cost of WGS continues to decline and becomes increasingly available, the ordering of rapid WGS for NICU patients with signs or symptoms of an underlying genetic condition is now feasible. However, many neonatal clinicians are not comfortable with the testing, and unfortunately, there is a dearth of geneticists to facilitate testing for every patient that needs it. Here, we will review the science behind WGS, diagnostic capabilities, limitations of testing, time to consider testing, test initiation, interpretation of results, developing a plan of care that incorporates genomic information, and returning WGS results to families.

OBJECTIVE Dural arteriovenous fistulas (dAVFs) of the superior sagittal sinus (SSS) are uncommon and represent 5%–12% of all intracranial dAVFs. SSS dAVFs can be divided into two main subtypes. The first type involves direct arterialization of the SSS, whereas the second type consists of a parasagittal arteriovenous shunt draining into a cortical vein directly lateral to the SSS and has retrograde cortical venous drainage with only secondary involvement of the SSS. Descriptions of the latter type of SSS dAVF are limited. As such, the authors present a consecutive case series of parasagittal SSS dAVFs from their institution. They detail clinical presentation, treatment strategies, and clinical and radiographic outcomes. METHODS The authors retrospectively reviewed a prospectively collected database of dAVFs that were treated between 2017 and 2023. All dAVFs characterized by an arterialized parasagittal vein directly lateral to the SSS were included in this study. Baseline demographic, clinical, radiological, treatment, and outcome-specific variables of interest were abstracted. RESULTS One hundred fifty-four dAVFs were seen at the authors’ institution over the 6-year period of interest. Eight (5.2%) were parasagittal dAVFs. At initial diagnostic imaging, 7 were Cognard grade III and 1 was grade IV. All patients initially underwent embolization of their dAVF. Three patients did not have complete obliteration of their dAVF after the first embolization. One patient underwent further treatment with repeat embolization, and 1 underwent microsurgical disconnection—both resulted in complete occlusion of the dAVF. Seven dAVFs were obliterated at final follow-up and 1 remained patent as the patient refused further treatment despite angiographic progression of dAVF. All symptomatic patients had resolution of their symptoms, and the average length of follow-up was 16.8 months. CONCLUSIONS Treatment of parasagittal dAVFs consists of occluding the proximal portion of the parasagittal arterialized draining vein. Endovascular therapy with liquid embolic agents is usually the first line of treatment. Surgical ligation is a valid option if the fistula cannot be successfully obliterated with embolization. Symptoms related to the SSS dAVF resolve after their obliteration.

OBJECTIVE Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.