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Effect of cochlear implantation on air conduction and bone conduction elicited vestibular evoked myogenic potentials-a scoping review.Background/Objectives: Cochlear implantation (CI) is an effective intervention for individuals with severe to profound hearing loss; however, it may impact vestibular function due to its proximity to related anatomical structures. Vestibular evoked myogenic potentials (VEMPs) assess the function of the saccule and utricle, critical components of the vestibular system. This review examines CI's impact on air conduction (AC) and bone conduction (BC) VEMP responses. Methods: A scoping review was conducted following PRISMA guidelines, using databases such as Medline, Embase, Cochrane Library, Scopus, and ProQuest Dissertations. Studies reporting on AC and/or BC-VEMP in CI recipients were included. Data extraction focused on VEMP response rates, amplitudes, and latencies pre- and post-CI. Risk of bias/quality assessment was performed using the Newcastle-Ottawa Scale. Results: Out of 961 studies identified, 4 met the inclusion criteria, encompassing a total of 245 CI-implanted ears. Results indicated that AC-VEMP responses were often reduced or absent post-CI, reflecting the influence of surgical changes in the middle ear mechanics rather than otolith dysfunction. In contrast, BC-VEMP responses were more consistently preserved, suggesting that BC stimuli bypass the middle ear and more accurately delineate otolith function. Variations in VEMP outcomes were noted depending on the surgical approach and individual patient factors. Conclusions: CI impacts vestibular function as measured by VEMP, with AC-VEMP showing greater susceptibility to postoperative changes compared to BC-VEMP. The presence of preserved BC-VEMP alongside absent AC-VEMP underscores the need to differentiate between these measures in assessing vestibular function.
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Self-reported penicillin allergy and antibiotic use in critical care: An observational, retrospective study.Background: Patients with Self-Reported Penicillin Allergy (SRPA) receive alternative antibiotics, which increase the length of stay and hospital costs, but the impact of SRPA on mortality in critically ill patients is not well described. Methods: This was a single-center, retrospective analysis of routinely gathered clinical data for all intensive care unit (ICU) admissions over nine years. The primary outcome was 28-day mortality, which was analyzed using a time-to-event approach with multivariable models to adjust for confounding factors, including age, comorbidities, sex, and admission SOFA score (as a measure of organ dysfunction). Antibiotic prescriptions during the ICU stay were also interrogated and compared. Results: Of 35319 admissions, 11.7% had SRPA. Compared with non-SRPA, patients with SRPA were more likely to be female (52.2% vs. 37.4%, p < 0.001) and had more comorbidities (p < 0.001) but had similar admission SOFA scores (median: 3.5 in both groups, p = 0.839). Patients with SRPA had significantly lower 28-day mortality (9.6% vs. 10.9%, p = 0.011). After multivariable adjustment for baseline characteristics, this effect persisted for unplanned (hazard ratio [HR]: 0.76, 95% CI: 0.68-0.86, p < 0.001), but not planned admissions (HR: 1.21, 95% CI: 0.92-1.58, p = 0.172). Whilst the duration of antibiotics in ICU was similar in the SRPA and non-SRPA groups (mean: 3.4 vs. 3.4 days, p = 0.663), the antibiotics used differed, with SRPA patients being significantly more likely to receive quinolones or other anti-Gram-positive antibiotics (p < 0.001). Conclusion: SRPA was associated with a survival benefit that persisted after adjustment for confounders for unplanned ICU admissions. Patients with SRPA were more likely to receive antibiotics that are not active against anaerobic bacteria. critical care, penicillin allergy, antimicrobial allergy, mortality, antimicrobial stewardship, acute care.
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Similar weight loss with semaglutide regardless of diabetes and cardiometabolic risk parameters in individuals with metabolic dysfunction-associated steatotic liver disease: Post hoc analysis of three randomised controlled trials.Aims: Weight loss mediated by glucagon-like peptide-1 (GLP-1) analogues is lower in patients with type 2 diabetes versus those without. Type 2 diabetes and obesity are risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD) and associated steatohepatitis (MASH). We evaluated weight changes in adults with MASLD/MASH with or without type 2 diabetes receiving the GLP-1 analogue semaglutide. Materials and methods: This was a post hoc analysis of data from three 48-72-week randomised trials investigating the effect of semaglutide versus placebo in adults with MASLD (NCT03357380) or biopsy-confirmed MASH (NCT02970942 and NCT03987451). Pooled data for semaglutide (0.4 mg once daily and 2.4 mg once weekly [n = 163]) and placebo (n = 137) were analysed at 1 year. Weight changes were analysed by type 2 diabetes status (type 2 diabetes [n = 209], pre-type 2 diabetes [n = 51] and no diabetes [n = 40]) and by other cardiometabolic risk parameters using analysis of covariance and Spearman's rank correlations. Results: The overall mean weight change was -11.1 kg (-11.7%) and -0.7 kg (-0.6%) with semaglutide and placebo, respectively. While numerically higher for people without type 2 diabetes, estimated treatment differences with semaglutide versus placebo were similar overall for people with type 2 diabetes (-10.2 kg; -10.8%), pre-type 2 diabetes (-9.8 kg; -10.2%) and no diabetes (-11.6 kg; -13.1%). Differences between groups were not statistically significant (p > 0.50 for all). Baseline fasting plasma glucose, glycated haemoglobin, insulin levels, insulin resistance and lipids did not correlate with weight change. Conclusions: People with MASLD/MASH had similar semaglutide-mediated weight loss regardless of type 2 diabetes status and other cardiometabolic risk parameters.
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Greater preservation of SARS-CoV-2 neutralising antibody responses following the ChAdOx1-S (AZD1222) vaccine compared with mRNA vaccines in haematopoietic cell transplant recipients.Whilst SARS-CoV-2 mRNA vaccines generate high neutralising antibodies (nAb) in most individuals, haematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell (CAR-T) recipients respond poorly. HSCT/CAR-T treatment ablates existing immune memory, with recipients requiring revaccination analogous to being vaccine naive. An optimal revaccination strategy for this cohort has not been defined. Factors predicting immunogenicity following three ancestral SARS-CoV-2 vaccines were assessed in 198 HSCT/CAR-T recipients and 96 healthcare workers (HCWs) recruited to multicentre studies. Only 25% of HSCT/CAR-T recipients generated nAbs following one dose, with titres 167-fold and 7-fold lower than that in HCWs after the first and second doses, respectively. Lower post-second dose nAb titres were associated with older age, rituximab use, and previous HSCT. ChAdOx1-S recipients were more likely to generate nAbs compared with mRNA vaccines, with titres comparable to HCWs. In contrast, nAbs were significantly lower in HSCT/CAR-T recipients than HCWs after mRNA vaccination. The poor first-dose immunogenicity in HSCT/CAR-T recipients suggests a minimum licensed dosing interval could limit the period of vulnerability following HSCT/CAR-T. The relative preservation of nAbs with ChAdOx1-S vaccination highlights the importance of evaluating alternative platforms to mRNA vaccination within this highly vulnerable clinical cohort.
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Sex differences in patients undergoing left main stem percutaneous coronary intervention for stable angina: data from a national registry.Background: Percutaneous coronary intervention (PCI) of the left main coronary artery (LMCA) for stable angina has steadily increased. Outcomes stratified by sex are inconclusive and limited. We assessed sex-based trends and differences in clinical outcomes among patients with stable angina who received LMCA PCI. Methods and results: We retrospectively collected data on patients with stable angina who underwent LMCA PCI (2006-2022) from the UK national PCI registry. The primary outcome of interest was inpatient mortality. Secondary outcomes were major bleeding and major cardiovascular and cerebral events. Multivariate logistic regression was used to assess adjusted odds ratio for outcome of interest. Of the 24 271 LMCA PCI performed, 5497 (22.7%) were in women. Women were older than men (median 72.7 versus 70.4) and less likely to have their PCI via radial access (50.3% versus 58.9%). More women had PCI guided by intravascular ultrasound (43.4% versus 41.2%). Women had significantly lower comorbid burden than men. Higher prevalence of chronic renal failure (6.72% versus 4.77%), smoking history (61.47% versus 45.68%), diabetes (27.36% versus 25.74%), prior myocardial infarction (45.36% versus 35.89%), and prior coronary artery bypass grafting (42.13% versus 30.34%) was observed in men than in women, respectively; P value <0.005 for all. Women had higher adjusted mortality (adjusted odds ratio, 1.63 [95% CI, 1.1-2.3]) and major bleeding events (adjusted odds ratio, 2.07 [95% CI, 1.19-3.59]). Although odds of major cardiovascular and cerebral events (adjusted odds ratio, 1.27[95% CI, 0.9-1.6]) were higher in women, it was not statistically significant. Conclusions: Despite being less comorbid, women had a significant increase in their mortality and major bleeding events following LMCA PCI. A sex-tailored approach considering age, intravascular imaging, and vascular access may improve outcomes.
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Functional analysis of fibroblasts and macrophages in head and neck paragangliomas.Background and aim: Head and neck paragangliomas (HNPGN) are tumours that carry significant morbidity The role of the stroma in the pathogenesis of HNPGN is not completely understood. This study explores the profile of fibroblasts and macrophages in HNPGN. Methods: Ten patients undergoing HNPGN surgery were recruited. CD68 and CD163 immunohistochemistry was performed for macrophage analysis; CD90 and podoplanin (PDPN) expression was examined to identify fibroblasts. RT-qPCR was performed on HNPGN tissue for macrophage- and fibroblast-associated molecules. Fibroblast cultures were established from HNPGN were analysed by RT-qPCR and flowcytometry. Confocal microscopy for MCT1 and MCT4 was performed in HNPGN. Results: CD68 and CD163 expressing macrophages were noted in HNPGN. CD90 and PDPN expressing cells were present in HNPGN. RT-qPCR analysis showed expression of phenotypic and functional macrophage- and fibroblast-associated molecules in HNPGN. RT-qPCR analysis of fibroblasts cultured from HNPGN confirmed the expression of several molecules including PDPN at comparable levels to healthy tissue fibroblasts. Expression of FAP, MCT-1, insulin receptor (CD220) and insulin growth factor receptor-2 (CD222) was noted on HNPGN derived fibroblasts on flowcytometry. MCT1 and MCT4 were expressed in HNPGN tumour cells and stromal macrophages in-situ. Conclusion: Fibroblasts and macrophages are present in the HNPGN tumour microenvironment, and several macrophage and fibroblast functional markers are expressed in HNPGN. Macrophages in HNPGN tissue express metabolic markers MCT1 and MCT4. Further analysis of the fibroblast and macrophage function in HNPGN will improve our understanding of their potential roles in tumour pathogenesis.
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Implantable and transcutaneous photobiomodulation promote neuroregeneration and recovery of lost function after spinal cord injury.Spinal cord injury (SCI) is a cause of profound and irreversible damage, with no effective therapy to promote functional recovery. Photobiomodulation (PBM) may provide a viable therapeutic approach using red or near-infrared light to promote recovery after SCI by mitigating neuroinflammation and preventing neuronal apoptosis. Our current study aimed to optimize PBM dose regimens and develop and validate the efficacy of an invasive PBM delivery paradigm for SCI. Dose optimization studies were performed using a serum withdrawal model of injury in cultures of primary adult rat dorsal root ganglion neurons (DRGN). Implantable and transcutaneous PBM delivery protocols were developed and validated using cadaveric modeling. The efficacy of PBM in promoting recovery after SCI in vivo was studied in a dorsal column crush injury model of SCI in adult rats. Optimal neuroprotection in vitro was achieved between 4 and 22 mW/cm2. 11 mW/cm2 for 1 min per day (0.66 J/cm2) increased cell viability by 45% over 5 days (p <0.0001), increasing neurite outgrowth by 25% (p <0.01). A method for invasive application of PBM was developed using a diffusion-tipped optogenetics fiber optic. Delivery methods for PBM were developed and validated for both invasive (iPBM) and noninvasive (transcutaneous) (tcPBM) application. iPBM and tcPBM (24 mW/cm2 at spinal cord, 1 min per day (1.44 J/cm2) up to 7 days) increased activation of regeneration-associated protein at 3 days after SCI, increasing GAP43+ axons in DRGN from 18.0% (control) to 41.4% ± 10.5 (iPBM) and 45.8% ± 3.4 (tcPBM) (p <0.05). This corresponded to significant improvements at 6 weeks post-injury in functional locomotor and sensory function recovery (p <0.01), axonal regeneration (p <0.01), and reduced lesion size (p <0.01). Our results demonstrated that PBM achieved a significant therapeutic benefit after SCI, either using iPBM or tcPBM application and can potentially be developed for clinical use in SCI patients.
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Mortality in septic patients treated with short-acting betablockers: a comprehensive meta-analysis of randomized controlled trials.Background: Treatment with short-acting betablockers in septic patients remains controversial. Two recent large multicenter trials have provided additional evidence on this therapeutic approach. We thus performed a meta-analysis, including the most recent data, to evaluate the potential impacts of treatment with short-acting betablockers on mortality in adult septic patients. Methods: The data search included PubMed, Web of Science, ClinicalTrials.gov and the Cochrane Library. A meta-analysis of all eligible peer-reviewed studies was performed in accordance with the PRISMA statement. Only randomized, controlled studies with valid classifications of sepsis and intravenous treatment with short-acting betablockers (landiolol or esmolol) were included. Short-term mortality served as the primary endpoint. Secondary endpoints included effects on short-term mortality regarding patient age and cardiac rhythm. Results: A total of seven studies summarizing 854 patients fulfilled the predefined criteria and were included. Short-term mortality as well as pooled mortality (longest period of data on mortality) was not significantly impacted by treatment with short-acting betablockers when compared to the reference treatment (Risk difference, - 0.10 [95% CI, - 0.22 to 0.02]; p = 0.11; p for Cochran's Q test = 0.001; I2 = 73%). No difference was seen when comparing patients aged < 65 versus ≥ 65 years (p = 0.11) or sinus tachycardia with atrial fibrillation (p = 0.27). Despite statistical heterogeneity, no significant publication bias was observed. Conclusion: Administration of short-acting betablockers did not reduce short-term mortality in septic patients with persistent tachycardia. Future studies should also provide extensive hemodynamic data to enable characterization of cardiac function before and during treatment.
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Diversity, inclusivity and traceability of mammography datasets used in development of Artificial Intelligence technologies: a systematic review.Purpose: There are many radiological datasets for breast cancer, some which have supported the development of AI medical devices for breast cancer screening and image classification. This review aims to identify mammography datasets (including digitised screen film mammography, 2D digital mammography and digital breast tomosynthesis) used in the development of AI technologies and present their characteristics, including their transparency of documentation, content, populations included and accessibility. Materials and methods: MEDLINE and Google Dataset searches identified studies describing AI technology development and referencing breast imaging datasets up to June 2024. The characteristics of each dataset are summarised. In particular, the accompanying documentation was reviewed with a focus on diversity and inclusion of populations represented within each dataset. Results: 254 datasets were referenced in the literature search, 190 were privately held, 36 had barriers which prevented access, and 28 were accessible. Most datasets originated from Europe, East Asia and North America. There was poor reporting of individuals' attributes: 32 (12 %) datasets reported race or ethnicity; 76 (30 %) reported female/male categories with only one dataset explicitly defining whether these categories represented sex or gender attributes. Conclusion: Through this review, we demonstrate gaps in the data landscape for mammography, highlighting poor representation globally. To ensure datasets in breast imaging have maximum utility for researchers, their characteristics should be documented and limitations of datasets, such as their representativeness of populations and settings, should inform scientific efforts to translate data-driven insights into technologies and discoveries.
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A systematic review of adult pineoblastomaBackground: Adult pineoblastoma is an extremely rare central nervous system malignancy. Limitations of tumour databases, single institution retrospective analyses and a few case reports are not sufficient to clarify treatment options. Therefore, a systematic review of comprehensive research data provides referenceable treatment options. Methods: A systematic review was performed using MEDLINE and Embase using the terms "pineoblastoma" and "adult". Relevant articles in the references were considered to supplement this systematic review. In addition, data were analysed using Kaplan-Meier survival curves, COX analysis, chi-square tests and log-rank tests. Results: A total of 108 adult cases from 32 articles were included in this study and the median age at diagnosis was 30 years. The 5-year survival rate was 49.5% (95% confidence interval: 0.378-0.602) and the 10-year survival rate was 33.9% (95% confidence interval: 0.207-0.476). During the 10-year follow-up period, Kaplan-Meier survival curves highlighted that the gross total resection was more beneficial than subtotal resection and no surgery (P=0.018). The treatment modality of radiotherapy and chemotherapy was beneficial for survival (P<0.001; P=0.020). In addition, multivariate COX analysis showed that radiotherapy was an independent factor in the beneficial prognosis (P<0.001) and gross total resection tends to improve survival within five years (P=0.079). Conclusion: For adult pineoblastoma, gross total excision and radiotherapy can be beneficial for survival.Systematic Review Registration: [website], identifier [registration number].
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Evaluation of an integrated variable flip angle protocol to estimate coil B for hyperpolarized MRI.Purpose: The purpose of this work is to validate a simple and versatile integrated variable flip angle (VFA) method for mapping B1 in hyperpolarized MRI, which can be used to correct signal variations due to coil inhomogeneity. Theory and methods: Simulations were run to assess performance of the VFA B1 mapping method compared to the currently used constant flip angle (CFA) approach. Simulation results were used to inform the design of VFA sequences, validated in four volunteers for hyperpolarized xenon-129 imaging of the lungs and another four volunteers for hyperpolarized carbon-13 imaging of the human brain. B1 maps obtained were used to correct transmit and receive inhomogeneity in the images. Results: Simulations showed improved performance of the VFA approach over the CFA approach with reduced sensitivity to T1. For xenon-129, the B1 maps accurately reflected the variation of signal depolarization, but in some cases could not be used to correct for coil receive inhomogeneity due to a lack of transmit-receive reciprocity resulting from suboptimal coil positioning. For carbon-13, the B1 maps showed good agreement with a separately acquired B1 map of a phantom and were effectively used to correct coil-induced signal inhomogeneity. Conclusion: A simple, versatile, and effective VFA B1 mapping method was implemented and evaluated. Inclusion of the B1 mapping method in hyperpolarized imaging studies can enable more robust signal quantification.
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Calculating optic nerve planning organ at risk volume margins for stereotactic radiosurgery using optic nerve motion determined using MRI.Objectives: The combination of sharp dose gradients in stereotactic radiosurgery (SRS) and minute optic nerve motion may significantly increase dose to the optic nerves when treating perioptic lesions. The aim of this study was to calculate optic nerve planning organ at risk volume (PRV) margins for CyberKnife SRS treatment planning. Methods: MRI scans were taken of 10 healthy volunteers looking left, right, up, down, and straight ahead to measure optic nerve motion. The measured optic nerve motion and the uncertainties in the technical accuracy of CyberKnife were used to calculate optic nerve PRV margins. Results: Two optic nerve PRV margins were calculated: a non-isotropic margin of mL/R,PRV=3 mm, mSup/Inf,PRV=2 mm, and mAnt/Post,PRV=1 mm which considers the full range of motion measured in a worst case scenario; and an isotropic margin of mPRV=1 mm which considers a scenario where patients are asked to look neutrally during imaging and treatment. Applying these PRVs to 8 historical sphenoid wing meningioma CyberKnife plans showed tolerance levels may be exceeded due to optic nerve motion. Conclusions: Optic nerve PRV margins may be needed in CyberKnife planning to reduce risk to the optic nerves. The use of a mPRV=1 mm PRV to account for organ motion, along with instructing patients to hold their gaze neutrally during imaging and treatment, may be a suitable organ sparing strategy. Advances in knowledge: Measured optic nerve motion and the technical accuracy of the CyberKnife system have been used to calculate optic nerve PRV margins.
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Laboratory-based molecular test alternatives to RT-PCR for the diagnosis of SARS-CoV-2 infection.Background: Diagnosing people with a SARS-CoV-2 infection played a critical role in managing the COVID-19 pandemic and remains a priority for the transition to long-term management of COVID-19. Initial shortages of extraction and reverse transcription polymerase chain reaction (RT-PCR) reagents impaired the desired upscaling of testing in many countries, which led to the search for alternatives to RNA extraction/purification and RT-PCR testing. Reference standard methods for diagnosing the presence of SARS-CoV-2 infection rely primarily on real-time reverse transcription-polymerase chain reaction (RT-PCR). Alternatives to RT-PCR could, if sufficiently accurate, have a positive impact by expanding the range of diagnostic tools available for the timely identification of people infected by SARS-CoV-2, access to testing and the use of resources. Objectives: To assess the diagnostic accuracy of alternative (to RT-PCR assays) laboratory-based molecular tests for diagnosing SARS-CoV-2 infection. Search methods: We searched the COVID-19 Open Access Project living evidence database from the University of Bern until 30 September 2020 and the WHO COVID-19 Research Database until 31 October 2022. We did not apply language restrictions. Selection criteria: We included studies of people with suspected or known SARS-CoV-2 infection, or where tests were used to screen for infection, and studies evaluating commercially developed laboratory-based molecular tests for the diagnosis of SARS-CoV-2 infection considered as alternatives to RT-PCR testing. We also included all reference standards to define the presence or absence of SARS-CoV-2, including RT-PCR tests and established clinical diagnostic criteria. Data collection and analysis: Two authors independently screened studies and resolved disagreements by discussing them with a third author. Two authors independently extracted data and assessed the risk of bias and applicability of the studies using the QUADAS-2 tool. We presented sensitivity and specificity, with 95% confidence intervals (CIs), for each test using paired forest plots and summarised results using average sensitivity and specificity using a bivariate random-effects meta-analysis. We illustrated the findings per index test category and assay brand compared to the WHO's acceptable sensitivity and specificity threshold for diagnosing SARS-CoV-2 infection using nucleic acid tests. Main results: We included data from 64 studies reporting 94 cohorts of participants and 105 index test evaluations, with 74,753 samples and 7517 confirmed SARS-CoV-2 cases. We did not identify any published or preprint reports of accuracy for a considerable number of commercially produced NAAT assays. Most cohorts were judged at unclear or high risk of bias in more than three QUADAS-2 domains. Around half of the cohorts were considered at high risk of selection bias because of recruitment based on COVID status. Three quarters of 94 cohorts were at high risk of bias in the reference standard domain because of reliance on a single RT-PCR result to determine the absence of SARS-CoV-2 infection or were at unclear risk of bias due to a lack of clarity about the time interval between the index test assessment and the reference standard, the number of missing results, or the absence of a participant flow diagram. For index tests categories with four or more evaluations and when summary estimations were possible, we found that: a) For RT-PCR assays designed to omit/adapt RNA extraction/purification, the average sensitivity was 95.1% (95% CI 91.1% to 97.3%), and the average specificity was 99.7% (95% CI 98.5% to 99.9%; based on 27 evaluations, 2834 samples and 1178 SARS-CoV-2 cases); b) For RT-LAMP assays, the average sensitivity was 88.4% (95% CI 83.1% to 92.2%), and the average specificity was 99.7% (95% CI 98.7% to 99.9%; 24 evaluations, 29,496 samples and 2255 SARS-CoV-2 cases); c) for TMA assays, the average sensitivity was 97.6% (95% CI 95.2% to 98.8%), and the average specificity was 99.4% (95% CI 94.9% to 99.9%; 14 evaluations, 2196 samples and 942 SARS-CoV-2 cases); d) for digital PCR assays, the average sensitivity was 98.5% (95% CI 95.2% to 99.5%), and the average specificity was 91.4% (95% CI 60.4% to 98.7%; five evaluations, 703 samples and 354 SARS-CoV-2 cases); e) for RT-LAMP assays omitting/adapting RNA extraction, the average sensitivity was 73.1% (95% CI 58.4% to 84%), and the average specificity was 100% (95% CI 98% to 100%; 24 evaluations, 14,342 samples and 1502 SARS-CoV-2 cases). Only two index test categories fulfil the WHO-acceptable sensitivity and specificity requirements for SARS-CoV-2 nucleic acid tests: RT-PCR assays designed to omit/adapt RNA extraction/purification and TMA assays. In addition, WHO-acceptable performance criteria were met for two assays out of 35 when tests were used according to manufacturer instructions. At 5% prevalence using a cohort of 1000 people suspected of SARS-CoV-2 infection, the positive predictive value of RT-PCR assays omitting/adapting RNA extraction/purification will be 94%, with three in 51 positive results being false positives, and around two missed cases. For TMA assays, the positive predictive value of RT-PCR assays will be 89%, with 6 in 55 positive results being false positives, and around one missed case. Authors' conclusions: Alternative laboratory-based molecular tests aim to enhance testing capacity in different ways, such as reducing the time, steps and resources needed to obtain valid results. Several index test technologies with these potential advantages have not been evaluated or have been assessed by only a few studies of limited methodological quality, so the performance of these kits was undetermined. Only two index test categories with enough evaluations for meta-analysis fulfil the WHO set of acceptable accuracy standards for SARS-CoV-2 nucleic acid tests: RT-PCR assays designed to omit/adapt RNA extraction/purification and TMA assays. These assays might prove to be suitable alternatives to RT-PCR for identifying people infected by SARS-CoV-2, especially when the alternative would be not having access to testing. However, these findings need to be interpreted and used with caution because of several limitations in the evidence, including reliance on retrospective samples without information about the symptom status of participants and the timing of assessment. No extrapolation of found accuracy data for these two alternatives to any test brands using the same techniques can be made as, for both groups, one test brand with high accuracy was overrepresented with 21/26 and 12/14 included studies, respectively. Although we used a comprehensive search and had broad eligibility criteria to include a wide range of tests that could be alternatives to RT-PCR methods, further research is needed to assess the performance of alternative COVID-19 tests and their role in pandemic management.
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Diagnostic performance of ultrasound vs. ultrasound-guided FNAc in thyroid nodules: data from the ElaTION trial.Introduction: ElaTION is a large multi-centre pragmatic randomised controlled trial, performed in 18 secondary/tertiary hospitals across England, comparing elastography ultrasound-guided fine needle aspiration cytology (EUS-FNAC) with ultrasound-guided FNAC (US-FNAC) alone in the diagnostic assessment of thyroid nodules. Secondary trial outcomes, reported here, assessed the accuracy of ultrasound-alone (US) compared with US-guided FNAC to inform and update current practice guidelines. Methods: Adults with single or multiple thyroid nodules who had not undergone previous FNAC were eligible. Radiologists assessed all thyroid nodules using US alone, thereby enabling assessment of its accuracy (sensitivity and specificity) versus US-FNAC. Results: Of the 982 participants, a final definitive diagnosis was obtained in 688, who were included in the final analyses. The sensitivity of US-alone was the same as US-FNAC (0.91, [95% CI 0.85, 0.97] vs 0.87 [95%CI 0.80-0.95], p=0.37). US alone had statistically significant lower specificity than US-FNAC alone (0.48 vs 0.67 respectively, p<0.0001). The malignancy rate on histology in a nodule classified as benign on ultrasound (U2) was 9/263 (3.42%) and on cytology (Thy2) was 15/353 (4.25%), whereas the malignancy rate in a nodule that was benign on both (U2, Thy2) was 3/210 (1.43%). Malignancy risk for U3, U4, and U5 nodules was 68/304 (22.4%), 43/83 (51.8%), and 29/38 (76.3%) respectively (p<0.0001). Yet 80/982 (8%) patients were discharged despite having U3-U5 scans with Thy1 (non-diagnostic) FNAC and no definitive diagnosis.Malignancy risk was higher in smaller nodules: <10mm 23/60 (38.3%), 10-20mm 46/162 (28.4 %), and >20mm 80/466 (17.2%) (p<0.0001). Nodules with indeterminate cytology with atypical features (Thy3a) carried a similar malignancy risk to those with indeterminate cytology (Thy3/3f): 27/95 (28.4%) versus 42/113 (37.2%) respectively (p=0.18). Conclusion: Ultrasound alone appears to be an effective diagnostic modality in thyroid nodules, confirming the recommendations of recent guidelines and the BTA classification. However, findings also suggest caution regarding existing recommendations for conservative management of non-diagnostic (Thy1/Bethesda I) and atypical (Thy3a/Bethesda III) nodules. In those cases, ultrasound (U3-5) features may help identify high-risk subgroups for more proactive management.
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Development of a conceptual framework for an electronic patient-reported outcome (ePRO) system measuring symptoms and impacts of CAR T-cell therapies in patients with haematological malignancies.Chimeric antigen receptor (CAR) T-cell therapy is associated with potentially severe toxicities that create a substantial burden for patients. Patient-reported outcomes (PROs) offer valuable insights into symptoms, functioning, and other complex constructs of interest. In this Review, we aimed to identify symptom and impact concepts important to patients receiving CAR T-cell therapy, construct a conceptual framework for an electronic patient-reported outcome (ePRO) system, and identify timepoints to capture PRO data for CAR T-cell therapies. We searched MEDLINE (OVID) and Web of Science (Clarivate) for articles in English published from Aug 30, 2017, to March 2, 2023. No restrictions on study design were applied. 178 symptoms or constructs were extracted from 44 articles reporting PRO collection in adults with haematological malignancies receiving CAR T-cell therapy. Six health-care professionals and 11 patients and caregiver partners verified construct relevance to clinical management and lived experience, respectively. 109 constructs were sorted according to the four domains of conceptual framework: symptom burden, impact of disease and treatment, tolerability, and health-related quality of life. The identification of concepts beyond symptom burden underscores the importance of PRO measurement for long-term monitoring, to align outcomes with patient concerns. The framework will facilitate PRO measure selection for systematic gathering of PROs from individuals with haematological malignancies receiving CAR T-cell therapies.
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Cancer and COVID-19: on the quest for effective vaccinesCancer vaccine development has been historically fraught with difficulty, but tremendous progress has been made over the past 5 years. In this In Focus article, we reflect on the progress and challenges with vaccine development for cancers in general and for hematologic malignancies in particular, and suggest how our cancer vaccine experience can offer insight into COVID-19 vaccination.
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Can symptoms of anosmia and dysgeusia be diagnostic for COVID-19?Objective: Olfactory and taste dysfunction (OTD) is a potential neurological manifestation of coronavirus-2019 (COVID-19). We aimed to investigate the diagnostic value of symptoms of anosmia and dysgeusia for COVID-19. Methods: A comprehensive electronic search was conducted using PubMed, MEDLINE, Scopus, Cochrane database, and Google Scholar from 1 June 2020 to 12 June 2020. All studies reporting symptoms of anosmia and dysgeusia in COVID-19-positive patients were included. A total of 23 studies were included in the systematic review. Results: Symptoms of anosmia and dysgeusia were frequently reported by COVID-19-positive patients. Symptoms were more common in females and in younger patients. There was no direct association between the severity of COVID-19 and the presence of symptoms. However, some evidence was found for a longer duration of these symptoms and increased severity of COVID-19 infection in young patients. Conclusion: OTD is commonly reported by COVID-19 patients. Due to limited literature on the association between OTD and COVID-19, it is currently not possible to conclude that these symptoms alone can be used to diagnose COVID-19. However, the presence of OTD can potentially be used as a screening tool for COVID-19 especially in young and female patients. Further research is required to establish the true diagnostic value of these symptoms and efficacy as screening tools for COVID-19 patients.
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Can a transition clinic bridge the gap between paediatric and adult inflammatory bowel disease care models?Transition care in inflammatory bowel disease is increasingly recognized as challenging given the inherent differences between paediatric and adult health care models, disease characteristics and treatment strategies. Transition is a dynamic process involving adolescents and young adults that are moving from a paediatric to an adult health care setting, and it should be flexible, continually updated and tailored to each patient. The implementation of a transition clinic is essential given the increasing incidence of the paediatric population with inflammatory bowel disease and the lifelong impact of this disease. The key question is when and how to structure transition according to the adolescent's clinical, psycho-social, educational needs and expectations to ensure continuity of care. In the attempt to improve the management of transition in inflammatory bowel disease and address the wide gap between adult and child care, we provide an update of the transition clinic and we propose a "treat to target" approach in transition to facilitate an effective and successful transition programme. In the changing landscape of the treatment of inflammatory bowel disease, further studies are necessary to determine the role of the transition clinic in determining the choice and strategy of therapy and its monitoring and the adoption of newer strategies such as biomarkers guided treating to target.