Citations

The activation and function of T cells is fundamental for the control of infectious diseases and cancer, and conversely can mediate several autoimmune diseases. Among the signaling pathways leading to T cell activation and function, the sensing of extracellular adenosine triphosphate (eATP) has been recently appreciated as an important component. Through a plethora of purinergic receptors, most prominently P2RX7, eATP sensing can induce a wide variety of processes in T cells, such as proliferation, subset differentiation, survival, or cell death. The downstream roles of eATP sensing can vary according to (a) the T cell subset, (b) the tissue where T cells are, and (c) the time after antigen exposure. In this mini-review, we revisit the recent findings on how eATP signaling pathways regulate T-cell immune responses and posit important unanswered questions on this field.

Patients with failed renal allografts have associated increased morbidity and mortality. The individualization of immunosuppression taper is the key element in managing these patients to avoid graft intolerance and sensitization while balancing the risk of continued immunosuppression. Most patients with uncomplicated chronic allograft failure do not require allograft nephrectomy (AN), and there is no clear evidence that it improves outcomes. The AN procedure is associated with variable morbidity and mortality. It is reserved mainly for early technical graft failure or in symptomatic cases associated with allograft infection, malignancy, or graft intolerance syndrome. It may also be considered in those who cannot tolerate immunosuppression and are at high risk for graft intolerance. AN has been associated with an increased risk of sensitization due to inflammatory response from surgery, immunosuppression withdrawal with allograft failure, and retained endovascular tissue. Although it is presumed that for-cause AN after transplant failure is associated with sensitization, it remains unclear whether elective AN in patients who remain on immunotherapy may prevent sensitization. The current practice of immunosuppression taper has not been shown to prevent sensitization or increase infection risk, but current literature is limited by selection bias and the absence of medication adherence data. We discuss the management of failed allografts based on retransplant candidacy, wait times, risk of graft intolerance syndrome, and immunosuppression side effects. Many unanswered questions remain, and future prospective randomized trials are needed to help guide evidence-based management.

Aims The aim of this study was to determine the prevalence of depressive and anxiety disorders prior to total hip (THA) and total knee arthroplasty (TKA) and to assess their impact on the rates of any infection, revision, or reoperation. Methods Between January 2000 and March 2019, 21,469 primary and revision arthroplasties (10,011 THAs; 11,458 TKAs), which were undertaken in 15,504 patients at a single academic medical centre, were identified from a 27-county linked electronic medical record (EMR) system. Depressive and anxiety disorders were identified by diagnoses in the EMR or by using a natural language processing program with subsequent validation from review of the medical records. Patients with mental health diagnoses other than anxiety or depression were excluded. Results Depressive and/or anxiety disorders were common before THA and TKA, with a prevalence of 30% in those who underwent primary THA, 33% in those who underwent revision THA, 32% in those who underwent primary TKA, and 35% in those who underwent revision TKA. The presence of depressive or anxiety disorders was associated with a significantly increased risk of any infection (primary THA, hazard ratio (HR) 1.5; revision THA, HR 1.9; primary TKA, HR 1.6; revision TKA, HR 1.8), revision (THA, HR 1.7; TKA, HR 1.6), re-revision (THA, HR 2.0; TKA, HR 1.6), and reoperation (primary THA, HR 1.6; revision THA, HR 2.2; primary TKA, HR 1.4; revision TKA, HR 1.9; p < 0.03 for all). Patients with preoperative depressive and/or anxiety disorders were significantly less likely to report “much better” joint function after primary THA (78% vs 87%) and primary TKA (86% vs 90%) compared with those without these disorders at two years postoperatively (p < 0.001 for all). Conclusion The presence of depressive or anxiety disorders prior to primary or revision THA and TKA is common, and associated with a significantly higher risk of infection, revision, reoperation, and dissatisfaction. This topic deserves further study, and surgeons may consider mental health optimization to be of similar importance to preoperative variables such as diabetic control, prior to arthroplasty. Cite this article: Bone Joint J 2023;105-B(5):526–533.

Background Machine learning (ML) is pervasive in all fields of research, from automating tasks to complex decision‐making. However, applications in different specialities are variable and generally limited. Like other conditions, the number of studies employing ML in hypertension research is growing rapidly. In this study, we aimed to survey hypertension research using ML, evaluate the reporting quality, and identify barriers to ML's potential to transform hypertension care. Methods and Results The Harmonious Understanding of Machine Learning Analytics Network survey questionnaire was applied to 63 hypertension‐related ML research articles published between January 2019 and September 2021. The most common research topics were blood pressure prediction (38%), hypertension (22%), cardiovascular outcomes (6%), blood pressure variability (5%), treatment response (5%), and real‐time blood pressure estimation (5%). The reporting quality of the articles was variable. Only 46% of articles described the study population or derivation cohort. Most articles (81%) reported at least 1 performance measure, but only 40% presented any measures of calibration. Compliance with ethics, patient privacy, and data security regulations were mentioned in 30 (48%) of the articles. Only 14% used geographically or temporally distinct validation data sets. Algorithmic bias was not addressed in any of the articles, with only 6 of them acknowledging risk of bias. Conclusions Recent ML research on hypertension is limited to exploratory research and has significant shortcomings in reporting quality, model validation, and algorithmic bias. Our analysis identifies areas for improvement that will help pave the way for the realization of the potential of ML in hypertension and facilitate its adoption.

Background: Cotesting with the Papanicolaou (Pap) and human papillomavirus tests detects most precancerous and cancerous lesions and increases the sensitivity for detecting high-grade precancerous and invasive cervical cancers compared with human papillomavirus testing alone. Objective: To compare the use of the Papette brush (hereafter Papette) to the traditional spatula with endocervical brush (cytobrush) for cervical cancer screening. Design: Pragmatic observational study. Methods: Adult women aged 21–64 years who were eligible for a Papanicolaou test at a Midwest Community Internal Medicine practice underwent cervical cancer screening using the Papette or spatula with cytobrush from 18 August 2021 through 1 February 2022. Cluster sampling was used across the practice. Pathology reports were then analyzed to compare the number of satisfactory versus unsatisfactory results between the two collection techniques. Results: We collected results for 756 Pap tests. The test results were satisfactory with the Papette 93.8% of the time compared with 93.0% for the spatula with cytobrush. Conclusion: The Papette is not inferior to a spatula with cytobrush as a collection method for Pap tests.

The radiotracer 1‐(2‐[18F]fluoroethyl)‐L‐tryptophan (L‐[18F]FETrp or [18F]FETrp) is a substrate of indoleamine 2,3‐dioxygenase, the initial and key enzyme of the kynurenine pathway associated with tumoral immune resistance. In preclinical positron emission tomography studies, [18F]FETrp is highly accumulated in a wide range of primary and metastatic cancers, such as lung cancer, prostate cancer, and gliomas. However, the clinical translation of this radiotracer into the first‐in‐human trial has not been reported, partially due to its racemization during radiofluorination which renders the purification of the final product challenging. However, efficient purification is essential for human studies in order to assure radiochemical and enantiomeric purity. In this work, we report a fully automated radiosynthesis of [18F]FETrp on a Synthra RNPlus research module, including a one‐pot two steps radiosynthesis, dual independent chiral and reverse‐phase semipreparative high‐performance liquid chromatography purifications, and solid‐phase extraction‐assisted formulation. The presented approach has led to its Investigational New Drug application and approval that allows the testing of this tracer in humans.

Background and purpose : Post-shunt MRI is usually performed at 1.5T under the general assumption that shunt-related susceptibility artifacts would be greater at higher field strengths. Purpose The purpose is to show that imaging post-shunt idiopathic normal pressure hydrocephalus (iNPH) patients at 3T is feasible and with reduced artifacts as compared to 1.5T. Methods We manually measured transverse dimensions of artifact at the levels of lateral ventricles, cerebral aqueduct, and cerebellar hemisphere. Areas/volumes of artifacts were calculated assuming an elliptic/ellipsoid shape. Relative extent of shunt-related artifact between field strengths was rated by 3 readers on a 5-point Likert scale. A Wilcoxon Signed Rank Test was used to compare artifact at 1.5T vs 3T for each sequence, with a significance level set at p < 0.05. Results Artifact areas were calculated in 22 iNPH patients; artifacts were on average smaller at 3T vs 1.5T on MPRAGE, DWI, and GRE sequences. On T2 FLAIR and T2 FSE, artifacts at 3T were larger than 1.5T. On the qualitative analysis, artifact effects were less at 3T vs 1.5T on DWI, greater at 3T on T2 FSE, and had mixed results on GRE. Conclusion Our results indicate feasibility of post-shunt imaging with the CERTAS Plus valve at 3T based on shunt-related artifact that is less than or equal in extent to that on 1.5T on most standard clinical imaging sequences. Our findings, corroborated by the qualitative image review, suggest that dedicated clinical imaging sequences for devices may allow for reduction in artifact extent at both 1.5T and 3T.